NICE recommends interim funding for GSK’s Zejula in ovarian cancer

Women with newly-diagnosed advanced ovarian cancer have a new treatment option in England after NICE recommend interim funding for GlaxoSmithKline’s Zejula (niraparib) in final guidance.

Zejula competes with AstraZeneca/Merck & Co’s PARP inhibitor class rival Lynparza (olaparib) but in this case it has an advantage in this maintenance therapy use as it can be used regardless of whether the BRCA mutation is present.

GSK estimates that around 3,000 people could benefit annually from the decision covering advanced high-grade epithelial ovarian cancer, fallopian tube or primary peritoneal cancer, who have completed and shown a response to platinum-based chemotherapy.

The drug will be paid for by the Cancer Drugs Fund, which provides interim funding until further data can be gathered that can help NICE with its cost-effectiveness calculations.

This indication is supported by data from the phase 3 PRIMA study, which enrolled patients with newly diagnosed advanced ovarian cancer following a complete or partial response to platinum-based chemotherapy regardless of biomarker status.

The primary endpoint in PRIMA was progression-free survival (PFS) analysed sequentially first in patients with BRCA-like mutations, then in the overall population.

Results showed Zejula significantly improved PFS regardless of biomarker status – in patients with homologous recombination deficiency (HRd) mutations, Zejula resulted in a 57% reduction in risk of disease progression versus placebo. 

In the overall population there was a 38% reduction in the risk of disease progression or death compared with placebo.

However NICE usually requires overall survival data before making decisions on long-term funding NHS funding.

As a result, the cost-effectiveness body has decided to use the CDF until GSK has the required survival data, it said in the guidance document.

In a managed access agreement with NICE, GSK has agreed an confidential discount to the list price of £4,500 for 56 100mg capsules, excluding VAT. Zejula pills are taken three times daily.

Poly-(ADP-ribose) polymerase (PARP) inhibitors are targeted therapies that work by exploiting cancer cells’ tendency to use a back-up system to keep control of mutations in their DNA.

By interfering with this process PARP inhibitors cause cancer cells to self-destruct as genetic defects mount, while leaving healthy tissue unaffected.

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2021 – UK market access prospects

With a new year comes the opportunity to think ahead for the market access landscape for the coming year. 2020 was a big year for market access initiatives in the UK, many of which are only just starting, and their impact will come through in 2021 and beyond. Looking back at key market access news from the last year, Leela Barham takes stock of what the next twelve months could bring for UK market access.

Whilst regulatory approval is only a starting step on market access, the UK has made steps to put the UK on the priority list for companies seeking marketing authorisation. The UK joined two initiatives in October 2020 that should bear fruit in the future: Project Orbis and the Access Consortium.

Project Orbis is coordinated by the US Food and Drug Administration and includes Canada, Australia, Switzerland, Singapore and Brazil and focuses upon review and approval of cancer treatments that offer promise. The Access Consortium includes some of the same players – Australia, Canada, Switzerland and Singapore – and looks more broadly at securing patient access to high-quality, safe and effective medicines. The ABPI has seen these as another way to help the UK deliver faster access.

The promise of faster market access 

Announced in December 2020, and beginning from 1 January 2021, the new licensing and access pathway (ILAP) at the Medicines and Healthcare Regulatory products Agency (MHRA) offers the chance – for a fee – for faster access for medicines that meet the criteria for the scheme. Criteria include that the condition is life-threatening or seriously debilitating or there is a significant patient or public health need.

“The UK has sought to provide incentives for development of new antibiotics by offering a volume neutral deal, also termed a Netflix approach”

Additional criteria include being an innovative medicine, such as an advanced therapy medicinal product (ATMP), significant new indication or a treatment for a rare disease or other special populations such as neonates, children, elderly and pregnant women and aligning with priorities of the UK, be that from the chief medical officer, the Department of Health and Social Care (DHSC) or those from the UK’s Life Sciences Sector Deal.

What is probably most exciting about ILAP is the bringing together of expertise from the MHRA with that of key HTA agencies NICE and the Scottish Medicines Consortium (SMC), as well as NHS England and NHS Improvement (NHSE&I), and, of course, patients too. It’s the first time that all these agencies are working together (much else draws on what has been available for some time; early advice and in parallel between NICE and MHRA).

2021 will reveal just how the ILPA will be operationalised and whichever product will be the first to go through the Innovation Passport stage – a new designation as part of ILAP – will help everyone understand how the criteria for the passport will apply in practice. It’ll also reveal just what the Target Development Profile (TDP) living document will cover and how it can evolve over time. This rolling review features is also another new element on offer under ILAP.

The Netflix approach

Antibiotics are vital to modern health care, yet there have been warnings for years that the economics at play simply don’t incentivise the development of new antibiotics; new antibiotics should be kept in reserve to limit antibiotic resistance and aren’t likely to be used in large volumes. The lack of new antibiotics is a problem when the existing antibiotics stop working.

The UK has sought to provide incentives for development of new antibiotics by offering a volume neutral deal, also termed a Netflix approach. In June 2017, NICE and NHSE&I launched a novel payment approach; offering up to £100 million to companies developing and marketing novel antibiotics based on the value of their products, regardless of volume sold.

2021 will see NICE trialling their adapted HTA approach for assessing the value of new antimicrobials. This will not only interest companies researching and developing new antibiotics, but other countries who will want to see whether the UK approach could work for them too. Where NICE leads, others will want to learn and adapt from.

Key access commitment due to report in VPAS 

The UK has a unique approach to managing the pricing of branded medicines through the 2019 Voluntary Scheme for Branded Medicines Pricing and Access (VPAS). The deal balances affordability commitments that benefit the UK government – where NHS spend on branded medicines cannot go above a pre-agreed level – with access commitments to industry.

A key commitment in the deal is to reach the upper quartile of uptake in relation to comparator countries for the five highest health gain categories of treatments. A timeline is set for hitting this too; it should be met during the first half of the scheme. That makes it a target for June 2021. Whilst there isn’t a timeline against it, there is also a commitment for the Department of Health and Social Care, NHSE&I and the industry association, the Association of the British Pharmaceutical Industry (ABPI) to better understand national and international variation on uptake and where that is unwarranted.

Realistically it’s seems unlikely that the timetable for the upper quartile target can be met. That’s because so far, based on desk research, there doesn’t appear to be a public list of the five highest health gains, and meeting minutes from operational reviews of the scheme suggest discussions have faced difficulties in agreeing them. It’s difficult both from a methods side (which countries, which treatments, etc) as well as data and time; COVID-19 has been a higher priority for many staffers involved. Expect a delay that may even see this reporting in 2022.

More change at NICE

2020 saw NICE consult on a variety of changes and set out plans on cross-cutting market access issues.

NICE started 2020 with the January publication of their principles; essentially a framework for how the agency goes about its work – from working on national priority areas through to publishing their work and updating as necessary.

NICE followed these in March 2020 with their final statement of intent on increasing the use of health and social data in their guidance. The statement covers one of the buzz phrases in market access – ‘real world data’ – and signals a greater willingness for NICE to consider its use in their work. The agency will keep working on how this will be implemented during 2021; this can only help, as much in the statement is aspirational and there’s not a great deal of clarity on exactly what NICE will accept, or not, as the case may be.

In June 2020, NICE let industry know about their changes to the process used in Single Technology Appraisals (STAs), moving from technical reports from Evidence Review Groups (ERGs) – independent academics – to present issues. That allows for easier engagement but also offers companies a right to reply to ERGs. With this change applied from STAs starting in May 2020, 2021 should see more companies seeing the difference. Efficiencies are the gain NICE hopes to see and that ties in with commitments to make NICE faster set out in VPAS. NICE hadn’t yet reached their targets according to metrics set out in July 2020 relating to appraisals up to Q1 of 2020, so 2021 could see NICE really getting to grips with getting faster.

NICE kept up the pace of consulting in 2020, setting out proposals to change the selection of treatments for evaluation in October 2020. The aim is for simplification as well as confirming promises made in VPAS that NICE will appraise all new active substances and significant new indications.

Arguably the most important consultation from NICE in 2020 was a six week consultation on the evidence and considerations for changing their methods, including those used in Technology Appraisals. According to experts at market access consulting firm, Bresmed, the changes being tabled that are likely to have a high potential impact include the removal of End of Life criteria to be replaced with a severity modifier, a change to the discount rate from 3.5% to 1.5% as well as greater emphasis on real world data.

Yet there is still more work for NICE and all stakeholders who will want to shape the final changes, as the agency plans to consult for another six weeks from February to March 2021 as well as consult with stakeholders on the draft programme manual which will encompass the reformed methods in June to July 2021.

The final changes won’t bear fruit for a little more time; implementation will be for treatments assessed from October 2021. This will also be when changes to selection processes will be implemented too. Companies are going to need to keep refining their inputs to NICE as they consult as well as run scenarios and review strategies to make the most of any opportunities for treatments that will be reviewed under the new approach.

Less clear is the ‘what and when’ of changes to the criteria that determine which treatments are reviewed through the NICE Highly Specialised Technologies (HST) programme, another area that NICE is reviewing. This is of interest as it offers a wider set of value components to be considered, as well as more flexibility on the cost-effectiveness threshold, for ultra-orphan treatments.

It’s likely NICE will set out details on this review during 2021. However, anyone hoping that the door will be open for the rarer end of common treatments could be disappointed as NICE say that they want to make the criteria clearer and more specific but not increase, or decrease, the number of HST topics. NICE is funded to do three a year.

NICE, building on their international links, was one of seven agencies who took part in the first ever World Evidence-based Healthcare Day in October 2020. We can expect to hear more on the global initiative in 2021. It’s also likely that their 2020 agreement with Colombia’s IETS will start to bear fruit, shaping how HTA is done in Colombia.

Pulling all this work together will also be a test of NICE’s 2020 appointed chief executive Gillian Leng. She’ll likely bring a steady hand to the consultation and the next steps, reflecting her over 13 years at NICE. 2021 could see big changes that should provide opportunities for faster NICE appraisals but as ever, the devil is in the detail and the full impact won’t be possible to see until a number of treatments have gone through the new methods and processes.

Medicines and Medical Devices Bill and a new Innovative Medicines Fund 

The Medicines and Medical Devices Bill is still going through Parliament and should become law in 2021. It’s part of the legal homework necessitated by the UK leaving the EU and covers a range of regulatory issues.

The importance of the Bill from a market access perspective is not however just about regulation but has also seen discussion of the establishment of an Innovative Medicines Fund. Whilst a proposed amendment to the Bill on establishing such a fund was withdrawn during December 2020, the discussions in the House of Lords suggested that NHSE&I and NICE will be engaging during the first quarter of 2021 on the fund.

The fund will replace the Cancer Drugs Fund (CDF), and widen the treatments that can be funded on an interim basis. The CDF as it has been run from 2016 helps generate evidence for treatments that have the potential to be cost-effective but face uncertainties that can be addressed through evidence generation. It’s proved to be a key enabler for market access for cancer drugs and many – although not all – drugs funded under the CDF have gone on to go into routine commissioning, although often with a hefty price cut. Just how the Innovative Medicines Fund will work is something to watch as it may provide new access opportunities previously not available.

More change ahead in 2022

There will be yet more change in the future with major shakeups expected in the way NHS England is structured, with the potential to abolish Clinical Commissioning Groups (CCGs) and Integrated Care Systems to be put on a statutory footing in 2022. That means much planning could be on the cards and, as ever, a need for the pharma industry to keep up to date and ensure that they’re engaging with those that matter for access on a local level.

About the author

leela barhamLeela Barham is researcher and writer who has worked with all stakeholders across the health care system, both in the UK and internationally, on the economics of the pharmaceutical industry. Leela worked as an advisor to the Department of Health and Social Care on the 2019 Voluntary Scheme for Branded Medicines Pricing and Access (VPAS).

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EMA says AstraZeneca’s COVID-19 shot could be approved on 29 January

The European medicines Agency (EMA) said this morning it has received a marketing application from AstraZeneca for its COVID-19 vaccine, already rolling out in the UK, and could give it the go-ahead later this month.

The filing for conditional marketing approval is scheduled for review by the EMA’s CHMP human medicine committee at a meeting on 29 January, and if all goes well it could be authorised on that day, according to the regulator.

The European Commission will then fast-track its decision-making process, says the EMA, with a view to granting a conditional marketing authorisation “within days”, a timeframe which was welcomed by Commission President Ursula von der Leyen.

AZ’s AZD1222 shot – which was developed with Oxford University – was cleared by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) on 30 December, and since then it has also been given emergency approval in several other countries including India.

The filing comes as the EU is facing criticism for the slow roll-out of its coronavirus vaccination programme as infection rates soar in the 27 member states.

While individual EU countries make the decisions about who to vaccinate, the Commission is coordinating the acquisition and allocation of supplies, and there have been complaints the process is taking too long.

The US and Britain have both vaccinated 1%-2% of their populations, according to an Economist report citing figures from the Our World in Data website, while Israel is leading the field at 16%. In contrast, Germany has managed just 0.4%, France didn’t cross the 1,000 threshold until 4 January, and the Netherlands only started vaccinating until 6 January.

So far the EMA has conditionally approved two coronavirus vaccines – Pfizer/BioNTech’s Comirnaty last month and Moderna’s candidate last week – and swift approval of the AZ vaccine should allow an acceleration in vaccination rates in the EU.

As it stands, the UK has vaccinated more people than the entirety of the EU combined, with the latest government figures indicating 2.3 million people have now received the first of two required doses, saying it plans to immunise all adults in the country by the autumn.

So far the effect of vaccination is imperceptible, however, as the UK recorded more than 46,000 new cases of COVID-19 yesterday, and 529 deaths, with NHS capacity creaking under the weight of over 32,000 people hospitalised with the infection.

The EU has 400 million doses of the AZ vaccine on order, part of a procurement programme that so far extends to 2.3 billion doses.

Last week the Commission said it intended to order an additional 200 million doses of the BioNTech/Pfizer, with the option to acquire another 100 million doses, taking its total to 600 million doses.

It has also agreed deals for the supply of 160 million doses of the Moderna shot, 400 million apiece for candidates in testing at Johnson & Johnson and CureVac, and 300 million of a Sanofi/GlaxoSmithKline candidate that has been delayed by clinical trial snags.

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Boehringer, Lilly’s Jardiance ties to match AZ’s Farxiga with heart failure label

Boehringer and Eli Lilly have moved closer to a heart failure indication for their SGLT2 inhibitor Jardiance, as the FDA starts a fast-track review of the drug in its first use beyond diabetes.

The US regulator is looking at data from the EMPEROR-Reduced trial of Jardiance (empagliflozin), which found that the drug achieved a 25% reduction in the combined primary endpoint of cardiovascular death or hospitalisation compared to placebo.

Lilly and Boehringer claim almost 60% market share for Jardiance among SGLT2 drugs used to treat type 2 diabetes, driving blockbuster sales for the brand.

It was the top-selling drug in the SGLT2 inhibitor class in 2019, with sales of almost $3 billion, helped by side-effect problems that have afflicted first-to-market rival Invokana (canagliflozin) from Johnson & Johnson.

However its rivals – which also include AstraZeneca’s Farxiga (dapagliflozin)  – have moved more swiftly into areas like heart failure and chronic kidney disease (CKD) which have made large numbers of new patients eligible for treatment with the class.

The new FDA review – covering Jardiance as a treatment for adults with heart failure with reduced ejection fraction (HFrEF) in patients with and without diabetes – is Lilly and Boehringer’s first chance to fight back.

Farxiga won FDA approval for adults with HFrEF in May 2020, which helped to drive its third-quarter sales up by a third to $525 million. AZ picked up EU approval for the same indication the following November.

Lilly and Boehringer will be hoping for a swift FDA review so that Jardiance will not fall too far behind its competitor in the heart failure category, and that looks likely as the benefit in HFrEF increasingly appears to be an SGLT2 class effect.

GlobalData has said that heart failure could add billions to the sales of the two SGLT2 inhibitors, particularly if they also claim approvals in heart failure with preserved ejection fraction (HFpEF), a larger patient population.

It says Farxiga will reach peak sales of $9 billion in 2028, with Jardiance forecast to reach $4.6 billion, assuming a launch for HFrEF this year. The bulk of those sales will come from HFpEF, however,  as in this form of heart failure there is a huge unmet need and no approved therapies.

Boehringer and Lilly are waiting for the results of the EMPEROR-Preserved later in 2021, while AZ should also Farxiga in the DELIVER trial in HFpEF, with additional data on both HFrEF and HFpEF due from the DETERMINE study, before year-end.

Meanwhile, EMPEROR-Reduced also showed a slowdown in the rate of decline in kidney function among patients with HFrEF, an effect that Lilly and Boehringer are exploring in the CKD patient population in the EMPA-KIDNEY trial due to generate results in 2022.

Invokana was the first mover among the SGLT2 drugs in the kidney area, winning FDA approval towards the end of 2019 for diabetic kidney disease. After a couple of years of declining sales due to concern about a risk of lower limb amputation, Invokana managed a 25% gain to $224 million in third-quarter 2020.

Farxiga meanwhile has already been filed for CKD on the back of the DAPA-CKD trial, with a verdict due in the second quarter.

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Moderna’s COVID-19 vaccine is third approved in UK

The UK has approved the Moderna coronavirus vaccine, hard on the heels of its go-ahead in Europe, although supplies are not expected to arrive for several weeks.

Moderna’s mRNA-1273 is the third COVID-19 vaccine to be approved for use by the Medicines and Healthcare products Regulatory Agency (MHRA) and is the second mRNA vaccine after Pfizer/BioNTech’s Comirnaty, which got the nod in December.

The UK government has ordered 17 million doses of the new vaccine, but none will be available before March, when Moderna is able to bring new production capacity online.

That means for now, the country’s immunisation programme will continue to rely on Comirnaty and the AstraZeneca/University of Oxford shot approved just before the New Year.

Around 1.5 million people in the UK have received at least one dose of either Pfizer/BioNTech or AZ vaccines, and that includes around a quarter of the over-80s age bracket who are particularly vulnerable to COVID-19.

The government’s target is to vaccinate 15 million people – around 22% of the total population – by the middle of next month.

The UK is facing a marked escalation in cases however, with the attest daily figures showing 68,000 new cases and 1,325 coronavirus-related deaths, and with a more transmissible strain of SARS-CoV-2 threatening to overwhelm the NHS.

The latest vaccine approval was welcomed by NHS Confederation chief executive Danny Mortimer, but he also stressed that “it does not mean the COVID-19 crisis today is over, especially as a major incident is declared in London, hospitalisations for coronavirus continue to rocket, and as many as one in 50 people are now infected.”

He went on: “It will…be weeks and months until the NHS feels the benefit of the vaccination programme.”

Moderna’s shot claimed conditional EU approval earlier this week, and the first supplies will start to arrive in Europe next week, according to Moderna. The European Commission has ordered 160 million doses, but Brexit means the UK will not benefit from the EU’s allocation and rollout plans.

Meanwhile, mRNA-1273 was also granted emergency use authorisation by the FDA on 18 December, with the US scheduled to receive 20 million doses by the end of 2020. Moderna has also said it aims to make 100 and 125 million more doses available in the first quarter of 2021, of which 85 to 100 million have been claimed by the US

The approval is based on trials showing mRNA-1273 had 94% efficacy in preventing disease, including in the elderly, roughly the same as the Pfizer/BioNTech shot and a little better than the 70% protection rate seen with AZ’s candidate.

The Oxfam charity welcomed that the UK now has more than enough vaccine on order to protect the entire population during 2021, but called for vaccine developers to share the science and technology behind them worldwide so less well-off countries don’t miss out.

“Nine in 10 people in the poorest countries are set to miss out on a vaccine unless the UK government and companies like Moderna urgently shift position,” said Oxfam’s health policy manager Anna Marriott.

“A failure to act is not just wrong but self-defeating and short-sighted – as long as the virus is allowed to spread in other parts of the world, public health and economic recovery in the UK will continue to be under threat,” she added.

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Unconvinced by NHS test run, NICE rejects BMS’ Opdivo in head and neck cancer

NICE has rejected Bristol Myers Squibb’s immunotherapy Opdivo as a second-line treatment for head and neck cancer in first draft guidance, unconvinced by evidence unearthed during a three-year NHS trial period.

In its latest guidance, NICE said that clinical trial data gathered so far and real-world evidence did not convince about the cost-effectiveness of Opdivo (nivolumab) in this use.

It said that Opdivo seems to produce a survival benefit in metastatic squamous cell carcinoma of the head and neck (SCCHN) compared with one of three possible standard therapies.

But there was too much uncertainty around the results and one of the comparators, the chemotherapy docetaxel, is already used as a standard treatment on the NHS.

As a result, NICE said there were doubts over the long-term survival benefit of Opdivo in this indication.

Cost-effectiveness estimates are likely to exceed the £30,000 per QALY threshold above which NICE considers drugs to be a waste of NHS resources.

While the manufacturer can submit further evidence following this first draft guidance, there is a chance interim funding could be discontinued if NICE comes to the same conclusions in final draft guidance.

Opdivo is currently available to NHS patients in England on the Cancer Drugs Fund after NICE agreed to fund it through the CDF in October 2017.

Following an initial rejection earlier that year, NICE asked (BMS) to submit a proposal for interim CDF reimbursement which could pay for Opdivo until stronger clinical data emerges and improves the argument that it is cost-effective.

BMS sweetened the deal with a commercially-confidential price cut and provided further information that convinced NICE to grant CDF funding.

Opdivo is a monoclonal antibody that binds to the PD-1 receptor, blocking its interaction with the PD-L1 and PD-L2 proteins.

This releases an immune response, allowing T-cells to interact with the cancer cells and destroy them.

Opdivo competes in several different cancer indications with a growing number of rival checkpoint inhibitors, although Merck & Co’s Keytruda (pembrolizumab) has become standard care in many indications and is the biggest seller in its class.

NICE will be consulting on its decision until 28th January.

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UK left trailing as EU quickly approves Moderna’s COVID-19 vaccine

The European Union has approved the coronavirus vaccine from Moderna, leaving the UK trailing because of changes to post-Brexit drug approval rules.

With the UK reeling from one of the worst outbreaks of the disease, it’s a worrying situation for one of the countries worst hit by the pandemic that is relying on vaccines to bring the virus under control.

The UK is in a national lockdown that could last into March, with more than 62,000 new cases and 1,000 coronavirus-related deaths recorded yesterday as a more transmissible strain threatens to overwhelm the country’s health service.

As things stand, the two rival mRNA-based vaccines from Pfizer/BioNTech and Moderna are now approved for use in the EU.

Meanwhile in the UK, the Pfizer/BioNTech and AstraZeneca shots have been quickly approved.

The UK government has an order for just 7 million shots of the Moderna vaccine covering just half a percent of the population, while the European Commission has secured 160 million doses, enough to cover around 18% of the population.

US-based Moderna said that first deliveries of the vaccine in Europe will begin next week.

Moderna’s vaccine is arguably the most effective approved so far at around 95%, while AstraZeneca’s rival that has been swiftly approved in the UK ahead of Europe works in around 62% of cases when given its recommend dose.

The Pfizer/BioNTech seems to be of comparable efficiency to the Moderna shot, and is being rolled out across the UK along with the AZ vaccine.

There is evidence to suggest the AZ vaccine’s efficacy could be improved to 90% by giving a half-dose to start with, but UK regulators have not been given sufficient evidence to approve this formulation.

After a rolling review began of Moderna’s vaccine late last year, the European Commission has issued a conditional marketing authorisation the day after it was backed by regulators from the CHMP scientific committee.

Moderna has said it is in talks with the UK regulator over approval, where European Commission decisions on medicines no longer automatically apply because of Brexit.

Under Brexit transition arrangements the Medicines and Healthcare products Regulatory Authority (MHRA) will continue to adopt decisions by the European Commission on medicines.

In usual circumstances companies are required to submit an identical filing request to the MHRA after a CHMP positive opinion

The UK regulator would then follow the decision of the European Commission, which nearly always rubber-stamps the CHMP’s decision within a few weeks.

But on this occasion the process has not been possible because of the accelerated timelines for vaccine approval because of the pandemic.

Questioned by pharmaphorum, the MHRA was unable to comment on arrangements for the Moderna vaccine at the time of writing.

However Moderna said separately that it is in talks with the MHRA to get the vaccine approved.

 

 

 

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Why cell therapy manufacture is a team sport

Louis van de Wiel, Vice President, Site Head EU Manufacturing, Kite, a Gilead Company, reveals the complexity that sits behind the process of individualised cell therapy – and why team culture makes it work

This thought leadership series has been paid and developed by Kite, a Gilead Company.

In 2018, we were preparing to build a European facility to produce individualised cell therapies for the treatment of cancer.

Roll on two years and the team has achieved what at the time appeared a major challenge, putting 1,000 tonnes of steel, 1,800 solar panels and 176km of network cable into the creation of a centre of excellence for cell therapy near Amsterdam in the Netherlands.

In my experience, completing the design and build of a facility such as this, through to qualification, licence and becoming fully operational, would normally take four to five years. Our ambition was always to do this within two years, a goal we achieved despite the unprecedented challenge of a global coronavirus pandemic.

Indeed, while undoubtedly putting new hurdles in our path, the arrival of COVID-19 into our lives has transformed our business and operations by presenting an opportunity to be adaptable, flexible and responsive – and to continually evaluate and mitigate risk.

“There is huge complexity involved in cell therapy manufacture, with hundreds of personnel responsible for ensuring the quality and supply of an individual patient’s cells”

It’s been a complex process that’s required highly technical and skilled personnel. Not only did we build a specialised facility from the ground up, but we built an organisation, from 10-15 people two years ago to more than 400 now. We put energy and emphasis into creating the right team and a culture where everyone understands the values and drivers, allowing us to operate in a collaborative and cohesive way.

Now the new €130 million, 19,000m2 manufacturing facility near Amsterdam is able to support delivery of up to 4,000 cell therapies each year for eligible cancer patients across Europe.

But backtrack to August 2018 and the very first European patients were also receiving treatment, part of an expertly crafted operation that ran in parallel to the build. Our supply chain group worked with the existing US team to manage the shipment of patients’ cells to the US for modification and their return for treatment.

Having a fully operational site in Europe versus the US has several advantages; reducing transportation time, strengthening the chain of custody and, potentially, cutting lead time to the patient by approximately one week. This allows us to potentially provide the therapy quicker for eligible cancer patients who have stopped responding to or have progressed despite other treatments. At this stage of their disease, for patients who have no other options, a week can make a difference.

The journey of the cell

The very nature of cell therapy manufacture means employees work in tightly controlled environments to ensure adherence to good manufacturing practice standards and, ultimately, to ensure the quality and integrity of the product.

Ultimately, it’s a team sport between Kite and Gilead and the 100-plus qualifying hospitals across Europe, all of which have been individually trained and assessed to ensure they are fully compliant with the necessary procedures and meet exacting standards.

So, what does the journey of the cell look like?

To achieve consistent, timely delivery of a high-quality product requires a robust and efficient approach to engineering patient’s own T cells, which in itself encompasses apheresis, cell modification and final formulation – coupled with rigorous quality control testing throughout – reflecting the highly complex nature of the manufacturing process.

Understandably, teamwork is vital and requires an integrated network and seamless communication between Kite and the treating hospital. The journey starts with the hospital making a treatment reservation through KiteKonnect and shipping of the apheresis kit to enable the process of extracting the patient’s own white blood cells, kickstarting both the chain of identity and chain of custody.

Here, our quality and supply chain experts are integral to every stage of the cell therapy manufacturing continuum to ensure the product is returned to the patient in a timely manner.

As soon as apheresis has completed, the cells are shipped in temperature-controlled conditions to our facility near Amsterdam where they are assessed for quality and condition. One patient equals one individual treatment, so it is critical to preserve the chain of custody and chain of identity to ensure the product comes back to the same patient.

Why chain of custody and identity is critical

The chain of custody and chain of identity must, therefore, go hand-in-hand. In this way, not only do we know which cells belong to which patient, but we have precise location and up-to-the-minute feedback on storage conditions to ensure quality and safety is paramount at all times.

Once the cells have completed this first stage, the manufacturing process can begin, with T cell selection, activation, and genetic modification using viral vector technology to ensure the ability to recognise the patient’s cancer cells. Cell expansion follows to multiply the modified cells into their millions.

Further critical quality testing then takes place to ensure the cells are of a required standard and to create a finished purified product, which will be stored and returned to the originator hospital in temperature-controlled conditions (see diagram below).

Several quality attributes will be tested at this stage and the cells must meet these rigorous criteria and specifications. There is huge complexity involved in cell therapy manufacturing, with hundreds of personnel responsible for ensuring the quality and supply of an individual patient’s cells.

As part of this process, the supply chain team simultaneously coordinate with the hospital to prepare the individual so when the cells are infused back to the patient they are primed to potentially fight the cancer.

Individualising the approach

In stark contrast to basic biopharmaceutical products with a robust starting material, the cells of a patient with cancer who has already undergone multiple treatments will not have the same quality. Consequently, there can be unforeseen hurdles during the process and I am proud that the team has managed each situation to safeguard the patient’s cells and ensure they receive treatment in an efficient and timely way.

This is particularly important when you consider the turnaround for each individualised product from starting material to the patient is typically four weeks – versus months or even years for a standard biopharmaceutical product.

Additionally, each patient equals one product batch – we do not keep inventory – and the potential impact on the patient if something happens to that batch is why we are so passionate. From quality manufacturing, facility engineering, supply chain, we’re driven to make sure the batch is returned to the patient safely and effectively.

What of the future? For me, it’s all about leadership, clarity, direction, and commitment of the entire team. It’s about the opportunity to be involved in an innovative field of cancer therapy where the body is stimulated to fight cancer cells. It’s about optimising the manufacturing process to become more effective and efficient. But, most of all, it’s about the patients, their care partners and families

 

This was supported by Kite, a Gilead Company
UK-CTH-2020-11-0075 | Date of preparation: December 2020

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FDA and doctors warn against extending COVID-19 vaccine dose gap

Tinkering with the dosing schedule of COVID-19 vaccines runs a “significant risk” to public health, the FDA has warned in a statement after the UK announced plans to prioritise the first doses of two approved shots.

The regulator made its comments after the UK announced a policy of stretching the gap between doses of the vaccine to up to 12 weeks to ensure maximum coverage of vulnerable groups.

The UK’s Joint Committee for Vaccines and Immunisation (JCVI) has recommended prioritising the first shot of the vaccines from Pfizer/BioNTech and AstraZeneca – but said that the follow-up booster dose can be delayed by up to 12 weeks.

According to the UK’s drug regulator the Pfizer/BioNTech vaccine doses should be taken at least 21 days apart while AZ vaccine’s booster doses should be given between four and 12 weeks apart.

But the FDA has issued a statement warning against such a strategy and reminded the public about the importance of receiving their second dose on time.

In the US, the Pfizer and BioNTech vaccine and a rival from Moderna is approved with a four-week gap between doses, but the AstraZeneca vaccine is not.

The FDA said it had been monitoring discussions and news reports about the policy and concluded that extending the time between doses, changing the dose and mixing and matching vaccines are “reasonable questions” to consider and evaluate.

But in a strongly-worded statement it said that changing the vaccine schedule without evidence could “undermine the historic vaccination efforts to protect the population from COVID-19.”

There are concerns elsewhere that the extended dosing schedule could also lead to resistant forms of the virus taking hold at a time when there is a new and highly infectious variant spreading through the UK.

In the US, doctors pointed out that the slow roll-out of the vaccines is due to logistical challenges rather than supply and urged authorities to focus on this rather than delaying the dosing schedule.

In the meantime, the UK government has pushed ahead with plans to vaccinate everyone in the four highest-priority groups by mid-February.

This will require the NHS to start delivering at least two million shots a week from next week.

AZ’s chief executive Pascal Soriot said it would be possible to manufacture the required vaccines, although it remains to be seen whether output will be increased in time to hit the target.

The government said it already has a batch of 530,000 doses and a further 450,000 are reportedly due to be available by the end of week according to Oxford University’s regius professor of medicine Sir John Bell.

Several million more doses of the vaccine are understood to have been manufactured but have not yet been bottled in vials.

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AZ COVID-19 vaccine cleared in UK, dosing to start next week

The UK has approved AstraZeneca and Oxford University’s COVID-19 vaccine AZD1222 in another significant step forward in the fight against the pandemic, with first doses due to be administered on Monday.

The UK government has already ordered 100 million doses of the adenovirus-based shot, enough to vaccinate 50 million people, adding to the 40 million dose order of the Pfizer/BioNTech shot – now known as Comirnaty – that was approved earlier this month.

The UK is the first country to approved AZD1222, and AZ says it is preparing to provide “millions of doses” in the first quarter of 2021, while building capacity for three billion doses for delivery worldwide by the end of the coming year.

The emergency approval comes as millions more people in the UK are facing tighter lockdown restrictions after another daily record of more than 53,000 confirmed new coronavirus cases yesterday.

Health Secretary Matt Hancock warned that while the rollout of AZD1222 brings forward the end of the pandemic, mass vaccination will take time and people should “hold their nerve” to avoid swamping the NHS in the first few months of 2021.

He told the BBC this morning that he now has “a high degree of confidence that we can be out of this by the spring.”

The Joint Committee on Vaccine and Immunisation (JCVI) has set out priority groups who will receive the vaccine, and as with the Pfizer/BioNTech jab first in line will be the over-80s and health and social care workers. So far, more than 600,000 people have received Comirnaty since dosing started on 9 December.

AZ chief executive Pascal Soriot said that millions of doses of AZD1222 have already been produced and are being filled, ready to ramp up supply as the UK immunisation programme gathers pace.

Soriot confirmed that AZ should be able to provide enough vaccine to meet the UK government’s target of a million doses per week “very rapidly” with the first doses due to be delivered to clinics “today or tomorrow.”

He also said that AZD1222 provides a reasonable level of protection from the coronavirus after a single dose, and as the second dose only needs to be given within 12 weeks, that provides an opportunity to immunise more people, more quickly.

In turn, that should start to reduce mortality and hospitalisation from COVID-19 and ease pressure from the NHS as cases continue to surge.

The AZ vaccine can also be stored, transported and handled at normal refrigerated conditions for at least six months making it more suitable for delivery to parts of the world with less sophisticated healthcare systems than the Pfizer/BioNTech shot, which requires colder storage.

Soriot also reiterated his view that AZD1222 should provide protection against the new, more transmissible strain of the SARS-CoV-2 virus that causes COVID-19.

The first case of that has now been identified in the US, along with dozens of other countries, but new research suggests that while it is easier to transmit it isn’t any more likely to cause severe disease.

The Medicines and Healthcare products Regulatory Agency (MHRA) has approved two full doses of AZD122, which has a top-line protective efficacy of 62%, as it decided there wasn’t enough data on a half dose/full dose combination that seemed to be more effective in trials with 90% protection rate.

The British Medical Association’s council chair Dr Chaand Nagpaul, welcomed the approval, but warned the rollout will require a massive step up in immunisation capacity.

“It is now crucial that supplies of this vaccine are given to as many GP practice sites and hospital hubs as possible and that this happens as quickly as possible so that we can begin vaccination en masse,” he said.

“We need to see a step change in distribution so that doctors can protect their patients and communities, beginning with those most at risk, and crucially this must include health and social care workers as they confront the virus on the front line.”

The BMA has previously said it is concerned about patchy access to the Pfizer/BioNTech vaccine by healthcare workers across the country.

EU orders another 100m doses of Comirnaty

The EMA is still reviewing the AZ vaccine, but yesterday exercised an option to acquire another 100 million doses of Comirnaty for distribution in the EU in 2021, taking the tally to 300 million doses.

Pfizer and BioNTech say they will be able to meet that order, agreed just two days after the first vaccinations against COVID-19 started in EU member states. The companies have previously said they will be able to supply up to 1.3 billion doses worldwide by the end of 2021.

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NICE backs AZ’s Forxiga for heart failure

Just a few weeks after its EU approval for heart failure, AstraZeneca’s Forxiga has been backed by NICE for this use by the NHS in England and Wales.

Forxiga (dapagliflozin) – originally developed as a type 2 diabetes drug – is the first SGLT2 inhibitor to be approved for the treatment of symptomatic chronic heart failure with reduced ejection fraction (HFrEF) in adults with and without diabetes.

It got a green light for this use in the EU in early November and in the US in May, with the new indication helping to drive third-quarter sales up by a third to $525 million.

Approval for Farxiga was based on positive results from the phase 3 DAPA-HF trial, which showed Farxiga achieved a statistically significant and clinically meaningful 26% reduction of death or hospitalisation for heart failure compared with placebo.

Today, NICE issued draft guidance which recommends Forxiga as an option for treating symptomatic HFrEF in adults if used as an add-on to standard drugs, which would make around 260,000 additional people eligible for treatment with the drug.

Novartis’ Entresto (sacubitril/valsartan) is also used to treat HFrEF, an indication which propelled it to sales of almost $2 billion last year.

According to NICE, while there are no head-to-head trials comparing Entresto and Forxiga, AZ’s drug “is likely to be as effective as [Entresto] at reducing the risk of death from heart disease

AZ’s rivals Eli Lilly and Boehringer Ingelheim meanwhile are also attempting to develop their SGLT2 inhibitor Jardiance (empagliflozin) for heart failure. They suffered a setback a year ago when the drug failed to improve exercise ability in two phase 3 studies, but bounced back with the results of the EMPEROR-Reduced study in July.

GlobalData has said that heart failure could add billions to the sales of the two SGLT2 inhibitors, particularly if they also claim approvals in heart failure with preserved ejection fraction (HFpEF), a larger patient population. It says Farxiga will reach peak sales of $9 billion in 2028, with Jardiance forecast to reach $4.6 billion, assuming a launch for HFrEF in 2021.

AZ is also putting Forxiga through its paces in heart failure in combination with other drugs, including its mineralocorticoid receptor modulator AZD9977 and selective endothelin A antagonist zibotentan (also known as AZD4054), with mid-stage trials on the go.

Meanwhile, heart failure is just one area into which AZ is hoping to expand Forxiga before its patents start to expire in the coming years. It’s also looking at chronic kidney disease (CKD), and has picked up a breakthrough designation from the FDA for this indication.

Forxiga was the first medicine to significantly prolong survival in patients with CKD, either with or without diabetes, in the DAPA-CKD trial.

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FDA rejects Novartis’ cholesterol drug after factory inspection issue

Novartis’ cholesterol drug inclisiran has hit a speed bump with the FDA, which has rejected the potential blockbuster because a manufacturing facility has yet to be inspected.

Matters appear to have been complicated by the pandemic and the travel disruption that it has caused, which is preventing an FDA team from visiting the plant in Europe.

In a statement the Swiss pharma said that the FDA has not raised any concerns about the safety or efficacy of the drug, which Novartis added to its pipeline after buying The Medicines Company for $9.7 billion late last year.

A first-in-class treatment discovered by Alnylam and then licensed to The Medicines Company, the drug is being developed for treatment for hyperlipidaemia in adults who have elevated low-density lipoprotein cholesterol (LDL-C) while being on a maximum tolerated dose of a statin therapy.

The FDA was due to make a regulatory decision on inclisiran by Wednesday but this has been delayed because of the unresolved “facility inspection-related conditions”.

Novartis said it will receive these requirements at the European manufacturing facility within 10 business days.

The FDA has not yet conducted a facility inspection and the FDA will set out a schedule if it deems one necessary, once safe travel may resume.

The European Commission has already approved the drug under the brand name Leqvio earlier this month following backing from the CHMP regulatory committee.

Inclisiran is a small interfering RNA (siRNA) therapy that works by inhibiting PCSK9 – the same target as Amgen’s Repatha (evolocumab) and Sanofi/Regeneron’s Repatha (alirocumab) – but is dosed only twice a year rather than every month.

Novartis hopes that the drug will make an impact where these antibody drugs have failed, with Repatha and Praluent lacking sales momentum despite being on the market for more than five years.

Payers had deemed the drugs to be too expensive and even price cuts failed to expand their use.

In January, Novartis and NHS England forged a pact to accelerate access to inclisiran for primary prevention of cardiovascular disease.

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Moderna’s COVID-19 vaccine is second for US after FDA green light

As expected, the FDA has moved swiftly ahead with emergency approval of Moderna’s COVID-19 vaccine after a positive assessment at its vaccines advisory committee.

The authorisation means that around six million more vaccine doses can now be rolled out in the US coronavirus immunisation programme, adding to the almost three million doses of Pfizer/BioNTech’s already-approved shot which started to be administered a few days ago.

The emergency use authorisation (EUA) for mRNA-1273 came the day after the FDA’s advisory panel voted 20-0 with one abstention that the benefits of the vaccine outweighed the risks for people aged 18 and over.

Moderna said delivery of supplies of mRNA-1273 will begin immediately, and reiterated its intention to provide 20 million doses to the US government out of its total order of more than 200 million before the end of this month.

The biotech now expects to have between 100 and 125 million doses available in the first quarter of 2021, of which 85 to 100 million have been claimed by the US.

On Friday meanwhile, the European Commission said it had exercised an option for an additional 80 million doses of Moderna’s product, taking its total order to 160 million doses. The UK has ordered seven million doses, Japan 50 million and South Korea 20 million.

The new supplies come as a quarter of a million new cases are being recorded each day in the US, the highest national rate in the world, with daily deaths averaging around 2,500 in the last couple of weeks.

Some US states re already saying they are unable to get access to promised supplies of Pfizer and BioNTech’s BNT-162b, as federal officials suggested manufacturing issues were at risk of holding up supplies of the shot – although that has been disputed by Pfizer. The US government’s objective is to have 100 million people vaccinated by April.

“It has been less than a year since the world first learned of SARS-CoV-2 and the terrible disease it can cause,” said Francis Collins, director of the US National Institutes of Health (NIH) which carried out clinical trials of mRNA-1273 and also contributed a technology used to stabilise the jab.

“To have not one but two safe and highly effective COVID-19 vaccines ready for deployment to the American public is truly a remarkable scientific achievement, and a significant step toward ending the pandemic that has caused so much suffering,” he added.

Moderna’s vaccine should be easier to distribute than the Pfizer/BioNTech shot as it requires temperatures of around -20 C for shipping – similar to a normal freezer – rather than -70 C.

The company has also updated its handling guide for the distribution for mRNA-1273 to include local transport under controlled conditions in a liquid state at 2-8 C, noting that “this important update eases the logistical burden of transporting the vaccine to more remote locations and ensures that the barriers to being vaccinated are lowered.”

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GSK’s Benlysta claims first FDA okay for lupus kidney damage

GlaxoSmithKline’s Benlysta has been on the market for almost a decade, but it still has some tricks up its sleeve – it’s just become the first and only FDA-approved treatment for lupus nephritis.

The US regulator has cleared both intravenous and subcutaneous formulations of Benlysta (belimumab) for the new indication, extending the use of the drug beyond its earlier label covering the treatment of active systemic lupus erythematosus (SLE) in combination with other medicines.

Originally approved in 2011 as an IV therapy for adults with SLE, a debilitating autoimmune disease, GSK got a green light for the subcutaneous formulation in 2017 and last year extended the label of the antibody to include paediatric patients aged over five.

Over that period sales have grown steadily to reach £514 million (almost $700 million) in the first nine months of 2020, boosted by its position as the only biologic approved to treat SLE. Approval in lupus nephritis is expected to push the product above the $1 billion threshold and into blockbuster sales territory.

Lupus nephritis is a severe form of SLE that can lead to late-stage renal failure and require dialysis or even a kidney replacement in the most severe cases. GSK estimates that around 60% of the 300,000-plus severe SLE patients in the US suffer from lupus nephritis each year, and a quarter of those develop end-stage renal disease.

The FDA approval comes on the back of the BLISS-LN trial results, which showed that 43% of patients on Benlysta hit the target of a significant improvement in kidney function, compared with 32% of those in the control arm.

GSK’s drug also improved secondary outcome measures including time to death or a kidney-related complication.

“What is interesting is more than 80% of eligible patients remain untreated with Benlysta in the US and of course even more around the world,” said GSK’s head of global pharma Luke Miels on the firm’s third-quarter results call.

“The number treated will increase further with the lupus nephritis indication and so there’s plenty of opportunity for growth,” he added.

GSK has been ramping up its manufacturing for Benlysta in anticipation of the new approval, including in-house capacity at its Rockville plant in Maryland, US, and through a contract manufacturing deal with Samsung Biologics.

GSK is also running a phase 3 combination study of Benlysta with rituximab, BLISS-BELIEVE, and the hope is that using the duo could drive the disease into clinical remission, according to Miels.

Both drugs work by targeting B cells, which are thought to be central to the disease process in SLE although the precise cause of the disease is unknown. Benlysta binds and neutralises the B cell survival factor BAFF, while rituximab targets CD20, a protein found on the surface of B cells.

The anti-CD20 mechanism could also lead to some competition for GSK in SLE and lupus nephritis. While Roche wasn’t able to show efficacy for its Rituxan brand of rituximab in trials, follow-up Gazyva (obinutuzumab) did better than placebo when added to standard care in the NOBILITY trial.

Another potential lupus nephritis rival is Aurinia Pharma’s voclosporin, which hit the mark last year in the phase 3 AURORA trial. AstraZeneca wasn’t so fortunate with its anifrolumab candidate, which flunked a pivotal trial in SLE in 2018, but still thinks it has potential.

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Operationalize: Expanded Access Programs Summit

Say Goodbye to the Worry & Uncertainty of Setting Up & Managing an Expanded Access Program

This inaugural Operationalize: Expanded Access Programs digital event is here to bring you solutions.

Dealing with a diverse and confusing global regulatory landscape, on top of an increasing number of access requests from patients, is no easy feat for people working in expanded access programs. As operational obstacles can arise at any time, from set up to close out, all stakeholders must equip themselves with the knowledge and tools to overcome these challenges.

By bringing together the world’s leading Expanded Access Programs thinkers, this exclusive platform will clarify the complex issues through end-to-end Managed Access/Compassionate Use program operationalization. Through open discussion, sharing best-practice case studies, and removing hypotheticals, this event provides an unrivalled opportunity to solve your challenges across the entire timeline.

Whether it’s Expanded Access ProgramsEarly Access,Managed AccessCompassionate UseNamed Patient Programsor even Post-Trial Access, ensure you aren’t repeating past mistakes by hearing global leaders recall their experience with a shared goal of providing you with pragmatic solutions to solve these complex hurdles.
Download the Full Event Guide to see what experts from Novartis, Stealth Bio, Santhera, Roche and Janssen will be discussing.

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Entresto set for big sales hike after FDA panel endorsement

Novartis’ Entresto is on course to become the first drug to be approved in the US for a form of heart failure that is notoriously hard to treat effectively, despite missing the mark in a phase 3 trial.

An FDA advisory committee 12 to 1 in favour of approving Entresto (sacubitril/valsartan) for heart failure with preserved ejection fraction (HFpEF), which accounts for around half of all heart failure cases but proves highly resistant to drug treatment. In HFpEF, the heart muscles pump normally but the organ is too stiff to fill properly.

Entresto is already approved to treat heart failure with reduced ejection fraction (HFrEF), caused by the heart muscles not pumping effectively, and has revitalised the treatment of patients with this form since its launch in 2015.

After a slow start, it has grown to become a $1.7 billion product last year, and that represented a surge from around $1 billion in 2018 revenues.

Analysts have predicted that approval in HFpEF – which affects around 3 million people in the US alone – could more than double Entresto’s sales, perhaps driving them as a high as $5 billion a year. There’s also plenty of upside in HFrEF as three out of four eligible patients are still not being treated with the drug, according to Novartis.

The prospect of adding HFpEF to Entresto’s label looked shaky last year however, when the drug missed its primary objective in the phase 3 PARAGON-HF trial.

The 4,822-patient study missed statistical significance for a composite primary endpoint of reducing cardiovascular death and total heart failure hospitalisations by 13% compared with valsartan alone, but only by a whisker, and Novartis has been upbeat since about the chances of approval.

The published data from the study suggested that the drug performed better in women, people with structural abnormalities in the left ventricles of their hearts, and those with very low ejection fractions – the amount of blood pushed out of the heart each beat.

The positive vote by FDA advisors came after the FDA reviewer acknowledged the narrow miss for statistical significance and pointed to the pressing need for a drug treatment for HFpEF.

The agency’s own expert said that “various pre-specified and post-hoc analyses suggest that sacubitril/valsartan compared to valsartan reduces HF events” in HFpEF, and of course Entresto’s long track record of safety stands in its favour.

While the FDA doesn’t have to follow its advisory committee’s advice it generally does, and Novartis is now eyeing approval of Entresto in HFpEF in the first quarter of 2021.

The main question now is exactly how the FDA will word the label if it approves the drug, with panellists debating the use of ejection fractions percentages to guide treatment with little agreement.

PARAGON-HF in included patients with left ventricular ejection fraction (LVEF) of 45% or more, but earlier studies have suggested the drug can have a benefit in people with scores below 40%.

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FDA backs Moderna COVID-19 shot ahead of emergency use vote

Moderna looks odds on to claim emergency use authorisation from the FDA for its COVID-19 vaccine this week, after the regulator published a report endorsing its safety and rating its efficacy at 94.5%.

The document has been published just after the US started the rollout of Pfizer and BioNTech’s vaccine after it got an emergency green light last week, and ahead of an expert panel due to consider Moderna’s shot on Thursday.

If the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) agrees with the agency’s assessment it could be available before the end of the week, accelerating the pandemic immunisation programme.

Like Pfizer/BioNTech’s BNT-162b, Moderna’s mRNA-1273 is based on messenger RNA coding for the SARS-CoV-2 spike protein, and will be administered in a two-dose regimen given a few weeks apart.

The FDA says no specific safety concerns with mRNA-1273 have been seen in the 30,400-patient COVE trial that underpins the EUA application, with minor effects like fever, headache and fatigue common but manageable, a serious side effects rare.

The overall 94.5% efficacy rating two weeks after the second dose is in line with interim data from the trial, although the FDA notes that it seems to be less effective in older people.

For the 18 to 64 age group efficacy comes in at 96%, but drops to 86% in the over-65s – both values are  way above the threshold that should be needed to support emergency use during the pandemic.

The shot also worked equally well in white, black and Hispanic subjects, men and women, and those with conditions like obesity and diabetes that increase the risk of severe COVID-19.

Importantly, there was also some preliminary data pointing to a reduction in asymptomatic SARS-CoV-2 infections – something that hasn’t yet been demonstrated with other vaccines – as well as prevention of severe disease.

All told, 38 trial participants in the placebo arm of the trial tested positive for asymptomatic COVID-19 at the time of their second dose, well above the 14 positives in the mRNA-1273 arm.

If the VRBPAC votes in favour of mRNA-1273 shipments are expected to begin within 24 hours, and Moderna has said it expects to be able to provide up to 6 million doses in the initial rollout, adding to around 3 million doses of the Pfizer/BioNTech jab.

The first doses of BNT-162b are being used to treat healthcare workers and elderly people in care homes, and it will be many months before vaccinations are available for all America’s 330 million population. Both vaccines will be provided free of charge to recipients.

The federal government has already signed supply agreements with Moderna and Pfizer/BioNTech for 300 million doses in 2021, enough to dose 150 million people. mRNA-1273 requires less intensive refrigeration that BNT-162b, so could be more suitable for distribution to more remote areas of the US.

There is also hope that vaccines from Johnson & Johnson and AstraZeneca could also be available in the first quarter of 2021.

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The critical role of the generics sector during the pandemic

Graeme Duncan from ADVANZ PHARMA explores how successful cross-industry collaboration between pharma and generics companies has helped support supply challenges during the pandemic.

While the world has had to come together to fight COVID-19, so too has the pharmaceutical industry in ensuring that essential medicines reach patients in need. Surges in demand have created challenges throughout the supply chain, from production line capacity to managing the shipment of products from one country to another. During this time, the role and responsibility of generics suppliers and manufacturers has been brought into stark perspective as one of the leading contributors in this industry-wide effort.

A synergistic relationship

There is a long-established synergistic relationship between larger, “innovation-driven” pharmaceutical companies and the generics industry in ensuring supply of established, but nevertheless essential, medicines. Despite this, the role of generics can often be overlooked, however its performance during this crisis has demonstrated its crucial importance and ability to respond to a series of considerable challenges.

Over the past year, we have witnessed first-hand how older, “less innovative” molecules have been integral for emergency treatment in hospitals, and also how they have been central to clinical trial research in identifying existing medicines that can be used to treat COVID-19. This demonstrates the need to keep specialised medicines available for patients, while also highlighting the potential of established treatments, which can be repositioned for use in new therapeutic areas based on their mode of action, therefore providing much-needed cost savings to healthcare systems.

“Now more than ever, it is our responsibility as a sector to ensure affordable access to healthcare and enable the future longevity of medicine development and supply.”

The pandemic has further highlighted how research is not strictly limited to large, “innovator” pharmaceutical companies. The generics medicines sector can, too, play a substantial part in discovering new areas for licensed products to be used in. Value-added versions of traditional medicines are one such way of innovating around existing molecules and, crucially, providing a better experience for patients through exploring new indications, changes to dosage or an improved formulation.

The role of the generics sector has also been able to complement the outputs from innovator companies in the development of COVID-19 vaccines and shows the crucial significance of working together to provide joint solutions to this exceptional global emergency. The industry is undoubtedly a competitive one, but such challenges cannot be tackled in isolation. Now is a time for togetherness and partnership in our duty to serve patients around the world.

Delivery of essential medicines

Many generic medicines are used in intensive care units globally, while others are used to treat chronic illnesses that do not go away irrespective of the pandemic. Ensuring continued supply of these medicines has been a primary aim and only been possible through connectivity with cross-industry partner networks and the adaptability and resilience of global teams.

From dialogue with production lines, through to manufacturing and shipping, there have been countless moving parts in a unified operation to ensure supply continuity. When we look back and reflect on these exceptional times, I am sure, as an industry, we will be extremely proud of the role each organisation and institution has played in the discovery of a vaccine and the delivery of essential medicines to those that need them most.

Ensuring healthcare sustainability

Now more than ever, it is our responsibility as a sector to ensure affordable access to healthcare and enable the future longevity of medicine development and supply. Value-added generic medicines provide an opportunity for society to address several healthcare inefficiencies, delivering improved health to patients, while essentially contributing to the sustainability of healthcare systems.

Whereas large pharmaceutical companies invest their resource and scientific knowledge to develop blockbuster treatments for patient communities with huge unmet needs, generics companies can centre efforts on everyday needs. All of which contribute to an intricate healthcare ecosystem, whereby patients can have access to effective treatments, regardless of their disease or condition. It’s vital that we continue to work together efficiently as an industry to ensure that every day medicines can pave the way for healthcare systems, including the NHS, to afford the latest innovations in diseases such as cancer. 

Brexit and the “second wave”

As we continue to navigate and understand the potential repercussions of the second wave of the pandemic, it’s imperative that we do not overlook its concurrence with Brexit in January 2021 and recognise the transition period we are continuing to work through. In our industry, it is vital that we have multifaceted supply models in place and include a number of contingency measures, such as ensuring the holding of safety supplies of medicines and creating a ‘buffer’ for stockholding.

Investment in dual sourcing is one such way companies can mitigate risks in order to safeguard supply and ensure demand can be met. We know that Brexit will inevitably bring change and we have to be familiar and aware of the effects it will have, but at the same time, as an industry we should feel well-prepared and confident that we will continue to maintain supply medicines during this pivotal period, and beyond.

Despite a large number of unknowns and uncertainty throughout the year, it’s been hugely inspiring to see the way the industry, and particularly the generics sector, has not only sustained its strength but also enhanced its dynamic support networks. The pandemic has undoubtedly acted as a catalyst to instigate new ways of working and has compelled us all to push the boundaries of what we thought possible, both at the business level and on a personal level. It’s crucial that we hold onto the fervid team spirit that we have established together, so that we can continue to find combined solutions as we move forward into a currently unknown landscape.

As we look ahead to 2021, the goal for patients and healthcare providers remains the same, however, this will now be viewed with a new, adjusted lens following our perspectives of, and lessons from this year.

New ways of working in this “new normal” era is something we are all still coming to terms with, but one thing that has been fiercely reignited is a commitment to collaboration and pulling together in times of need. 2021 sees new and exciting launches for generics companies as they look to expand across Europe and bring more complex medicines to patients and healthcare systems.

About the author

Graeme ADVANZ PHARMAGraeme Duncan has been the Chief Executive Officer of ADVANZ PHARMA since the summer of 2018. Prior to this Graeme led the international segment of the business covering its global operations. Graeme has 25 years of healthcare and life science experience across innovative, branded generics, generics and services organisations. He has held senior management and executive roles in organisations including GSK, IVAX, Healthcare at Home and AMCo.

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Pfizer/BioNTech COVID-19 vaccinations start across the US

Hospitals in the US have started vaccinating their front-line staff against COVID-19, as deaths in the country crossed the 300,000 threshold with more than 200,000 new cases reported yesterday.

Shipments of Pfizer/BioNTech’s mRNA vaccine BNT-162b are being shipped to hundreds of hospitals and other distribution facilities across the US, with the first three million doses earmarked for  healthcare workers and elderly.

Just three days after the FDA granted Emergency Use Authorisation for the shot, the first dose administered outside a clinical trial was given yesterday to intensive care nurse Sandra Lindsay at the Long Island Jewish Medical Center in Queens, New York.

It’s likely to be months before all eligible healthcare workers for the first wave receive vaccinations. Hopeful eyes are already turning to the Moderna’s mRNA-1273 vaccine, which is scheduled to be reviewed by FDA advisors on Thursday, to help boost available supplies.

The first nursing home residents aren’t expected to start receiving their doses until next week, according to Army General Gustave Perna, chief operating officer for Operation Warp Speed, the US vaccination task force.

The immunisation programme comes as hospitals around the country say they are already struggling to cope with the influx of COVID-19. The US has the highest death toll from the disease worldwide, ahead of Brazil, India and Mexico, and there are fears of a further spike as the holiday season gathers pace.

The US government is predicting that 20 million Americans will have received at least one of the two doses of the vaccines by the end of the year, with another 30 million set to be immunised during January and another 50 million by the end of March.

President Trump took a break from his relentless tweeting about alleged election fraud to briefly acknowledge the milestone on the path to recovery from the pandemic.

Canada also gave the first doses of BNT-162b to healthcare workers yesterday, a week after the UK started the ball rolling on its own vaccination programme – the first to get started in the world.

Because BNT-162b is made from RNA, it has strict temperature requirements and has to be stored at -70 C in dry ice to prevent it from breaking down, although it can be kept at regular refrigeration temperatures temporarily – around three days – after being defrosted for administration.

That will pose a logistical challenge for all countries, requiring a massive and carefully controlled shipping operation as doses come off the production line at Pfizer’s facility in Michigan.

Around 5 million doses of Moderna’s vaccine could be ready to ship straightaway if the FDA gives a green light, possibly as soon as Friday, with distributor McKesson handling that roll-out. Moderna’s shot is a little easier to handle as it only needs to be kept at -20 C.

Meanwhile, Operation Warp Speed’s chief executive Dr Moncef Slauoi also suggested yesterday that Johnson & Johnson could get approval for its shot in late January or early in February, while AstraZeneca may be in a position to seek FDA approval as early as February.

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Family doctors begin COVID-19 immunisation drive in UK

The roll-out of the biggest vaccination programme in the history of the UK’s NHS is gathering pace, as family doctors and their teams begin taking delivery of Pfizer/BioNTech’s COVID-19 shot.

In a statement the NHS said that GP practices in more than 100 parts of the country are taking delivery of the vaccine today.

Some clinics will begin immunisations this afternoon and the majority will start tomorrow (Tuesday), the NHS said.

The vaccine, which was approved in the UK earlier this month, will be administered by teams of nurses, paramedics and pharmacists.

Those aged over 80, as well as care home workers and residents, will get the vaccine first as they are considered to be in the group at highest risk of getting the disease.

Care home residents will start to receive the vaccine later this week as distributors finalise the processes to deliver the Pfizer/BioNTech vaccine, which must be stored at around -70c to maintain its integrity.

Practice teams are redesigning sites to put in processes to meet these logistical challenges and the NHS will contact people in the priority groups when it is their turn to receive the vaccine.

Dr Simon Hodes, a GP from Watford told the BBC that his surgery is due to begin vaccinations on Monday, adding that very few of his patients had worries about the shot.

Hodes said his surgery had introduced a “military-style operation” to ensure vaccine doses are not wasted.

Dr Nikki Kanani, a practising GP and NHS director of primary care, said: “GPs, nurses, pharmacists and other primary care staff are eager to play their part in protecting people against coronavirus.

“This is the greatest vaccination programme ever undertaken by the NHS and, to help vaccinate people safely we will be working with local communities to deliver it in convenient and familiar settings.

“As a GP I am proud to be part of this huge national effort to protect our patients against the virus and I would urge the public to come forward when they are called up for the vaccine.”

Feature image copyright BioNTech SE 2020, all rights reserved

 

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Sanofi/GSK trial woes delay a billion COVID-19 shots by nine months

Sanofi and GlaxoSmithKline have said their COVID-19 vaccine has hit a snag in clinical development, prompting analysts to note this could delay delivery of potentially more than a billion shots globally by up to nine months.

Interim results from a phase 1/2 clinical trial show the immune response from Sanofi/GSK’s vaccine produced a lower immune response in older adults.

While antibody levels were comparable to those seen in recovering COVID-19 patients in adults aged 18-49, the response was lower in older adults.

This was likely due to an insufficient concentration of the antigen, according to a team of analysts from Jefferies investment bank, who said the companies have decided to investigate an improved formulation.

This demonstrated rapid viral clearance in a challenge study in non-human primates.

A phase 2b study is expected in February next year with support from the US government agency, the Biomedical Advanced Research and Development Agency (BARDA).

This could lead to a phase 3 study next summer and an authorised product at the end of next year delaying deliveries of potentially more than a billion shots, enough to protect half a billion people.

The US government has an agreement to buy 100 million doses, with an option for another 500 million doses and has funded development to the tune of $2.1 billion.

The European Commission has an agreement for 300 million doses, the UK has ordered 60 million doses and the Canadian government has ordered 72 million doses.

AZ to combine vaccine with Russian rival

In a separate development it has emerged that AstraZeneca is to test its whether its COVID-19 vaccine can be combined with a component used in Russia’s Sputnik V shot, according to a statement the government-backed Russian Direct Investment Fund (RDIF).

Clinical trials so far have shown that Sputnik V, which uses two different types of viral vector to produce an immune response, provides protection in around 90% of cases.

The RDIF, which has helped bankroll the vaccine, said AZ had accepted a proposal to begin trials of its AZD-1222 in combination with Sputnik V’s human adenoviral vector type Ad26 by the end of the year.

AZ has already announced findings suggesting that using an initial lower dose of the vaccine produces a protection level of around 90%, while using two maximum strength doses produced protection levels of just over 60%.

The idea behind Sputnik V, developed by a team of scientists from Moscow’s Gamaleya Center, is to use two shots using different viral vectors to reduce the risk of the body developing resistance and not producing a boosted immune response to the second booster shot.

AZ’s vaccine, developed in partnership with Oxford University, looked like one of the most promising vaccine candidates until it was hit with a safety scare that caused trials to be put on hold for a few weeks in September.

While regulators later decided that trials could continue, the announcement that researchers had accidentally stumbled on the low-dose high-dose combination did not go down well and caused the company’s share price to tumble.

 

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CLL patients in England to get AZ’s Calquence after okay from NICE

NHS England is to grant immediate access to AstraZeneca’s cancer drug Calquence (acalabrutinib) for certain patients with chronic lymphocytic leukaemia (CLL) after NICE backed it in first draft recommendations.

NICE recommended regular NHS funding for Calquence in CLL who are considered high-risk due to 17p deletion or TP53 mutations.

It is also recommended for adults with CLL who have had at least one previous treatment and only if AbbVie and Janssen’s class rival Imbruvica (ibrutinib) is their only suitable treatment option.

NHS England is granting access via an interim funding arrangement with AstraZeneca, which will end 30 days after publication of positive final guidance, after which treatment will be funded by routine commissioning budgets.

However the guidance has rejected Calquence for a third group of patients with untreated, non-high risk CLL who are unsuitable for treatment with chemotherapy.

AZ said it will provide further data analyses for continued discussions with NICE about this group of patients.

Calquence was approved in CLL by the EMA last month as monotherapy or in combination with Roche’s Gazyvaro (obinutuzumab).

In CLL, too many blood stem cells in the bone marrow become abnormal white blood cells, and these have difficulty in fighting infections.

As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells, and platelets. This could result in anaemia, infection, and bleeding.

B-cell receptor signalling through Bruton’s tyrosine kinase (BTK) is one of the essential growth pathways for CLL.

In B-cells, BTK signalling results in the activation of pathways necessary for growth: proliferation, trafficking, chemotaxis, and adhesion.

Calquence binds selectively to BTK, inhibiting its activity.

This is the second recommendation of a therapy for CLL in the space of a month – in November it recommended AbbVie/Roche’s chemotherapy-free option of Venclyxto (venetoclax) and Gazyva.

NICE’s decision allows for a 12-month fixed duration treatment option based on data from the phase 3 CLL14 trial.

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Bluebird trumpets long-term data from beta-thalassaemia gene therapy

bluebird bio has presented long-term data from its Zinteglo one-time gene therapy for the blood disorder beta-thalassaemia, as the company continues talks with payers in Europe to bring the ultra-pricey treatment to market.

The European Medicines Agency (EMA) has granted a conditional marketing authorisation for the drug that will be marketed as Zinteglo (betibeglogene autotemcel), meaning its licence must be renewed each year until confirmatory data is available.

Results announced at the American Society of Hematology could help bluebird make the case for the long-term use of the therapy as the treatment approaches the market in Europe.

In the US, Zinteglo has hit a speed-bump with the FDA, which is asking for more information about production facilities before a review of clinical data can begin.

Of the 10 patients enrolled in the ongoing long-term study (LTF-303) from a phase 3 programme, 9/10 (90%) were transfusion independent (TI) and all these patients remain transfusion independent.

David Davidson, chief medical officer at bluebird, said: “All of the patients in our phase 3 studies who achieved transfusion independence have maintained it, with the durability of the treatment effect underscored by patients from our earlier studies reaching their five-year anniversaries of freedom from transfusions. “

In a group of patients aged under 18 from the Northstar-2 and Northstar-3 phase 3 studies, 87% (13 out of 15) achieved TI and remained so.

In a long-term follow-up 53% of patients who achieved TI and restarted iron chelation have since stopped and 30% who achieved TI now receive phlebotomy to reduce iron levels.

Davidson added: “Transfusion independence has been observed in paediatric, adolescent and adult patients and across genotypes – suggesting outcomes with this gene therapy may be consistent regardless of age or genotype.”

In Europe bluebird has set a price of up to $1.58 million euros for a single shot.

This is paid in instalments, with 315,000 euros paid up front and four additional payments due only if the treatment continues to be effective.

Zinteglo is already launched in Germany and is nearing the end of its year of free pricing.

But it’s fair to say that the therapy won’t come cheaply even though most member states will likely end up negotiating a lower price

In England, cost-effectiveness body NICE is reviewing Zinteglo and is due to publish draft document early in the new year.

Although it’s too early to say how the review will go, NICE will be looking for more certainty on the long-term effects of the therapy.

The latest data won’t be part of the submission to NICE, but the company hopes that an ongoing review of the cost-effectiveness body’s methodology will help novel gene therapies get to market.

Nicola Redfern, general manager of bluebird bio UK, is hopeful that NICE will refine its existing Quality Adjusted Life Year (QALY) and find better ways to deal with uncertainties in clinical data.

“How we deal with uncertainties is going to be fundamentally important,” she said.

Another issue to address is the discount rate NICE uses to calculate the value of medicines and their long-term impact on patients’ lives.

The 3.5% discount rate currently used means that these benefits reduce quickly over time in the view of NICE and Redfern agrees with NICE’s own proposals to adopt the 1.5% discount rate used by the Treasury.

“We agree with NICE that there is already evidence to bring it in line with the rate in the Treasury Green Book.”

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Sanofi on notice as FDA reviews GSK’s Nucala for nasal polyps

Sanofi and Regeneron’s Dupixent has had the US market for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) mainly to itself since June 2019, but GlaxoSmithKline’s Nucala is now breathing down its neck.

The FDA has started its review of Nucala (mepolizumab) for the inflammatory condition, which results in the growth of nasal polyps in the nose that can obstruct airflow and cause mucus discharge, sometimes requiring surgical intervention.

In severe cases, polyps recur, so patients have to undergo multiple operations that according to GSK progressively become less effective and more risky.

The anti-IL-5 antibody is already approved by the FDA for severe asthma and two other conditions – hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis – and is one of GSK’s top growth products with sales rising 28% to more than $930 million in the first nine months of this year.

If approved, it will be the first biologic challenger to Dupixent (dupilumab) – which has a different mechanism of action targeting IL-4 and IL-13 – and would also keep Nucala ahead of IL-5 class rivals like Teva’s Cinqair (reslizumab) and AstraZeneca’s Fasenra (benralizumab) that are challenging it in asthma.

The FDA’s review centres on the SYNAPSE trial, which involved 400 patients with a history of previous surgery who were in need of another procedure due to growing polyps and severe symptoms.

The drug improved both the size of nasal polyps at week 52 and in nasal obstruction during weeks 49-52, compared to placebo when added to standard of care, and extended the time to surgery by 57%.

Standard care for CRSwNP consists of corticosteroids in the nose, after surgery and systemic corticosteroids, but these often lack efficacy.

AZ reported positive results with Fasenra in CRSwNP in September, so may not be far behind with its own regulatory filings, and has also started to catch up with first-to-market Nucala in sales terms, growing 34% to $666 million in the first three quarters of 2020.

Regeneron meanwhile said last month that CRSwNP has been helping to drive increased sales of Dupixent, with a “strong uptick” in prescribing for this indication this year as well as a good performance in other uses like atopic dermatitis that drive it to more than $1.1 billion in global sales in the third quarter alone.

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First COVID-19 vaccinations begin in UK hospitals

A 90-year-old woman has become the first person given a COVID-19 vaccine as part of the UK’s mass vaccination programme.

Margaret Keenan was given the injection at 06:31 this morning at University Hospitals Coventry and Warwickshire NHS Trust.

Keenan turns 91 next week and the BBC said she described receiving the shot as “the best early birthday present”.

It was the first of 800,000 doses of the Pfizer/BioNTech vaccine that will be given in the coming weeks, and up to four million more are expected by the end of the month.

The logistical challenges of storing and distributing the vaccine, which must be kept at around -70C to retain its integrity, mean that distribution will occur at around 50 hubs nationally.

Keenan said: “I feel so privileged to be the first person vaccinated against COVID-19, it’s the best early birthday present I could wish for because it means I can finally look forward to spending time with my family and friends in the New Year after being on my own for most of the year.

“My advice to anyone offered the vaccine is to take it – if I can have it at 90 then you can have it too!”

NHS nurse May Parsons said it was a “huge honour” to be the first in the country to deliver the vaccine to the patient.

NHS England chief executive Sir Simon Stevens added: “Less than a year after the first case of this new disease was diagnosed, the NHS has now delivered the first clinically approved COVID-19 vaccination – that is a remarkable achievement.

“Today is just the first step in the largest vaccination programme this country has ever seen. It will take some months to complete the work as more vaccine supplies become available and until then we must not drop our guard.

“But if we all stay vigilant in the weeks and months ahead, we will be able to look back at this as a decisive turning point in the battle against the virus.”

The vaccine has also been given to the first person in Wales, where 48 year-old Craig Atkins from Ebbw Vale became the first to receive the shot.

Wales has been hit badly by the virus and unlike England the numbers of cases are continuing to rise, prompting the country’s devolved government to consider a third national lockdown as hospital cases rose to a record high.

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Scotland says no to Daiichi Sankyo’s cholesterol drug Nilemdo

The Scottish Medicines Consortium (SMC) has rejected Daiichi Sankyo’s new cholesterol-lowering drug Nilemdo for use by NHS Scotland, saying the evidence backing the drug isn’t strong enough.

The SMC verdict comes ahead of a decision south of the border by NICE, which was scheduled to discuss Nilemdo (bempedoic acid) at a committee meeting a month ago but hasn’t yet published the outcome of its appraisal.

The SMC said yesterday that after reviewing the data from four phase 3 studies, Daiichi Sankyo “did not present sufficiently robust clinical and economic analyses to gain acceptance”.

Originally developed by US biopharma company Esperion, Nilemdo was approved by the European Medicines Agency (EMA) in April, a couple of months after it got a green light from the US FDA as Nexletol. It launched last month in Germany, and is due to roll out in the UK early next year.

Both the European and FDA approvals cover use of the drug to lower LDL cholesterol in patients with abnormally high cholesterol or established atherosclerotic cardiovascular disease who are already on maximum-tolerated statin therapy or cannot tolerate statins, both alone and in combination with ezetimibe.

Analysts have previously suggested that Nexletol/Nilemdo may become a blockbuster product, perhaps bringing in as much as $3 billion a year at peak.

That could however prove tougher to achieve if other health technology assessment (HTA) agencies follow the SMC’s lead and deny reimbursement for the drug.

The Institute for Clinical and Economic Review (ICER) in the US published a draft report on Nexletol last month, which concluded that the drug was unlikely to be cost-effective at its current prices, although that is still open for comment.

Meanwhile, there are other potential obstacles to Nilemdo reaching its ambitious sales projections.

High peak sales projections for drugs to treat high cholesterol haven’t always been accurate, as can be seen from a glance at the sales figures for Amgen’s Repatha (evolocumab) and Sanofi/Regeneron’s Praluent (alirocumab) – injectable PCSK9 inhibitors also indicated as add-in therapy to statins – which have been lacklustre since launch.

Esperion and Daiichi Sankyo’s drug has the advantage of being taken in tablet form once a day, but it could also see stiff competition from Novartis’ Leqvio (inclisiran), which also targets PCSK9 but requires dosing with a needle just twice a year. It is due for EMA and FDA verdicts before year-end and is also tipped to make multibillion-dollar sales.

ICER’s draft report suggested that inclisiran’s efficacy and price meant that it was approaching the acceptable cost-effectiveness threshold at an anticipated price of around $5,600 per year – roughly the same as Repatha and Praluent.

Daiichi Sankyo will be hoping for better news from NICE and other European HTAs, particularly as it recently renegotiated European rights to Nilemdo and ezetimibe combo product Nustendi, paying a second $150 million milestone payment to take ownership of the European approvals for the two drugs.

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UK faces “V-Day” and largest ever vaccination programme

Tuesday has been dubbed “V-day” in the UK, when the first doses of Pfizer/BioNTech’s coronavirus vaccine will be distributed to the public outside of a clinical trial.

Health secretary reportedly Matt Hancock came up with the wartime analogy to describe what will be the largest scale vaccination programme in the country’s history.

The UK last week became the first country in the world to officially authorise the vaccine, which has so far shown an effectiveness of around 95% and minimal side effects in a late-stage clinical trial.

But the logistics of delivering the vaccine are hugely challenging, with up to 4 million sent out this month alone.

The most at-risk groups of people will be first to get the vaccine, with people in care homes, those aged over 80 and healthcare workers targeted first.

On top of this is the requirement for the cutting-edge RNA-based vaccines to be stored at ultra-low temperatures.

According to Luxembourg-based cold chain specialist B Medical Systems, demand for ultra-cool freezers has gone “off the chart” in recent weeks.

Pfizer’s vaccine needs to be stored at around -70C to retain its integrity, while its rival from Moderna that is under review by regulators needs to be stored at -20C.

The company has developed a product that can operate as both a vaccine freezer and a vaccine refrigerator, which could be used to store the Pfizer/BioNTech and Moderna vaccines, as well as the potential shot from AstraZeneca that requires standard refrigerator temperatures for storage.

However the waiting list for the vaccine fridges is expected to grow as more and more companies authorise various coronavirus vaccines.

CEO Luc Provost said: “Normally we would be supplying 2,000-3,000 units typically for a country. We expect this to increase 5-7 fold to some 15,000 units at least. In places like India we are seeing orders reach six figures.”

The biggest challenge is maintaining an unbroken “cold chain”, something that is already common in medicine logistics, but more challenging on this occasion because of the specialist requirements of the vaccine and the sheer scale of the operation.

According to Provost the biggest challenge will be distribution within the UK and other countries and in particular “the last mile” to the patient.

“Vaccine wastage happens in two areas – in-country transport and vaccine administration at health facilities.

“Most portable vaccine carriers and cold containers cannot keep cold beyond 12 hours, especially if it is hot outside.

“Transportation for the last mile to where the immunisation is happening – for example care home residents which will be amongst the first in the UK to get vaccinated – is time consuming and monitoring this journey presents a big problem.”

Feature image copyright BioNTech SE 2020, all rights reserved

 

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Latin America: How pharma can navigate a complex market

Bureaucracy, political upheaval, and lack of regulations continue to make Latin America a difficult market for European and North American pharma to enter – and COVID-19 has only worsened these issues. Developing market specialist Dr Zulf Masters OBE takes us through the nuances of being successful in this region.

Having worked all around the world to supply medicines to developing markets, Dr Zulf Masters understands the biggest barrier for a pharma company entering these regions is a lack of understanding of their complexities.

His company, UK-based Masters Speciality Pharma, partners with big pharma, SME and biotech companies to bring their products to patients in developing markets. Although Latin America is a vast and varied region, it is one that, generally, presents difficulties for the industry as access to treatments is limited.

“There are a number of companies that, even in the last decade, have left the Latin American market completely because they just couldn’t handle the local nuances, such as devaluation of currencies, economic problems, political issues, the bureaucracy and, dare I say, quite a lot of corruption,” Dr Masters says.

Political issues in some countries are among the most conspicuous challenges in the region, and Dr Masters says they continue to “create havoc”.

“Sometimes this havoc can cause a huge swing in economic issues and lead to significant losses if you’re not careful.

“For example, during the impeachment time of Dilma Rousseff in Brazil, business with public healthcare completely dried up. We had to be nimble and move very quickly to start working with HMOs and the private sector to remain profitable.”

Thankfully, many governments are working towards emulating systems from other countries to make their healthcare systems more robust. For example, price regulations are becoming more common in Latin America, often being based on models such as NICE’s.

“Companies from North America and Europe tend to be used to thinking in fairly logical systems – but in Latin America, bureaucracy is not always logical”

“Several countries have brought in regional harmonisations and regulations, and the regulatory environment is becoming increasingly sophisticated and complex,” says Dr Masters. “Our medical and regulatory team have started teaching partners all over Latin America to embrace developing world regulatory and pharmacovigilance tactics and programmes.”

However, increased regulation can be a double-edged sword – they increase safety and efficacy but can also make access to medicines more difficult in many markets.

“National budgets are squeezed because drugs like new biologics are very, very expensive,” says Dr Masters. “National budgets are not used to spending $84,000 per patient per year for just one person who has hepatitis C. They are becoming very, very selective in what they can import.”

As a result, Latin American countries often end up importing products from cheaper but less-regulated markets like India and China, leading to some counterfeit medicines being introduced into the supply chain.

“It’s a big task for people like us in the industry to educate these systems and explain what they’re doing wrong,” Dr Masters says.

These regulations have also resulted in many essential COVD-19 products becoming unavailable in Latin American countries.

Colombia’s recent price regulations, for example, resulted in a lack of products like Midazolam, an anesthesia for people on ventilation.

“Because the price regulations are so drastic, many companies who had registered products like Midazolam had left the country by the time COVID came,” Dr Masters explains.

He adds that the pandemic has brought to light the fragility of healthcare systems in the region.

“Governments and individuals have found out that pandemic strategies are not easy to handle when you have very draconian bureaucracies in place. Locking down ports and airports added additional problems because most of these companies, even those who manufacture locally, have to depend on APIs coming in from China and India. The entire supply chain was disrupted, and the cost of logistics often increased tenfold.”

But like in other regions, healthcare systems are finding innovative ways to get around the unique problems posed by COVID.

“In countries like Brazil, where many people live in poor areas far away from centres of excellence or clinics, telemedicine and remote consultations have become very important. That trend is likely to accelerate.”

Finding solutions

Dr Masters says that many of these issues can best be sidestepped by industry and government working together.

“It has to be an almost symbiotic relationship where we’re helping each other out and showing governments the right way to do things. We need to encourage them not to take paths that will lead to more counterfeit medicines entering their markets, because they will never come back from that.”

Dr Masters believes that having a local presence and employing local people can help companies better understand the cultures and economies of these regions.

“Companies from North America, Europe and other developed areas tend to be used to thinking in fairly logical systems,” he says. “In Latin America, bureaucracy is not always logical. It’s important to be well-informed, adapt yourself and find the right partnerships.”

He uses the example of sickle cell disease product Siklos, which Masters was attempting to bring into Brazil.

“The product was already registered by the FDA, but the Brazilian regulators decided they were above the FDA and started asking questions that were often irrelevant.

“Sickle cell disease patients in the Northeast of Brazil are generally poor and in desperate need of this medication, but the country will drag its feet and put up roadblocks.

“Health authorities and governments will have to rethink their strategies and reduce the barriers to entry if this situation is to improve.”

Similarly, Latin America is not part of many smaller biotech companies’ business models when they are first starting out, but partnering with companies local to the region that are organised according to EU/US laws can derisk the venture and help expand access beyond what they would normally be able to achieve.

“At Masters, for example, we do a lot of market research into disease areas and disease prevalence, and even do some local clinical trials if needed. Then we feed this information back to the company, and when the product is registered by the FDA we will look at licensing it into our markets and registering them locally.”

But Dr Masters says he is confident that the market will change.

“There are many emerging markets in Latin America who are always looking to North America and Europe as being the standard-bearers of drug regulation, and they are changing the way they think based on what they’re seeing there. They’re talking to those people to see how they can regulate their prices properly and equitably.”

The industry has an important role to play in helping these governments in this transition.

“Helping facilitate these discussions and connections, providing education and conducting local trials are all steps the industry can take to help open up these markets even further for other companies.”

About the interviewee

Zulf Masters, CEO of Masters Speciality Pharma, started his career back in 1980 working at Beecham as a medical rep, moving into international sales and marketing for certain emerging markets. This gave him the idea of founding Masters in 1984 to address the unmet patient need in emerging markets. The company began by serving the Caribbean from a single location from where, as Founder and CEO, Zulf has led Masters into becoming a truly international business. Masters Speciality Pharma is today a global pharmaceutical company, headquartered in the UK, with a 35-year successful track record in supplying medicines to hospitals, clinics, and government organisations in more than 75 countries.

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Social media erupts as anti-vaxxers respond to COVID-19 vaccine approval

In the midst of the jubilation about the UK’s emergency approval of Pfizer/BioNTech’s COVID-19 shot in the UK came the depressingly inevitable round of anti-vaccine social media activity and lobbying.

The green light for BNT162b was swiftly followed by posts on Twitter likening the vaccine to thalidomide – the drug that notoriously resulted in thousands of children being born with birth defects in the 1960s.

That ignores the fact that the thalidomide tragedy itself was responsible for the introduction of evidence-based medicine and reforms to the regulatory system that keep patients safe today.

While thalidomide is trending in the UK, it’s worth noting that many tweets are being posted by people slamming the #antivaxxers – a hashtag that is currently also riding high.

The Medicines and healthcare products regulatory Agency (MHRA) has been warning for some against anti-vaccine rhetoric that it fears could derail the coronavirus vaccination programme – which would be larger than any adult campaign carried out to date.

Pre-empting the backlash, MHRA’s chief executive Dr June Raine said at a Downing Street press briefing that despite the speed of its review, completed just three weeks after the final data were made available, no corners had been cut.

The vaccine had been approved after “an extremely thorough and scientifically rigorous review of all the evidence of safety, of effectiveness and of quality,” she asserted, adding: “The safety of the public will always come first.”

As the vaccine starts to be distributed, the National Institute for Biological Standards and Control (NIBSC) will be carrying out independent lab tests to confirm that every single shot that goes out meets the required standards for safety and quality, according to Raine.

Anti-vaxxers have been responsible for promulgating a series of fantastical rumours and conspiracy theories about coronavirus vaccines, including a persistent claim that vaccination will result in people being implanted with a microchip that will be used to track them.

Other false claims are that RNA-based vaccines like BNT162b can alter a recipient’s DNA and that the shots will contain tissue from aborted foetuses.

While some of these are frankly comical, the fear is that the spread of misinformation into mainstream media sources could result in fewer people taking up the opportunity to be vaccinated, undermining the programme.

Research published by the Vaccine Confidence Project – a unit of the London School of Hygiene & Tropical Medicine – found that misinformation around a COVID-19 vaccine induced a fall in the willingness to receive it among those who would otherwise “definitely” vaccinate.

VCP’s study found that only 54% of UK people would definitely have a COVID-19 vaccine – higher than the 41% seen in the US – with most of those who were reluctant citing safety concerns or a sense the threat posed by the pandemic had been overblown.

That’s already fewer than is required for herd immunity – a level of protection that would impact on virus transmission – but most worrying was that exposure to misinformation reduced the proportion of those definite responses by more than 6%.

“I hope that enough people take these vaccines, but I think it is going to be much more of a challenge than is recognised,” VCP director Heidi Larson told the Financial Times this week.

Speaking to the BBC today, Pfizer’s country manager for the UK, Ben Osborn said that “after the provision of clean water, vaccines are…the single most effective public health intervention we can make”. He also stressed that the study behind the approval was assessed by an independent panel with no links to Pfizer and BioNTech.

Health secretary Matt Hancock has also responded to questions about the anti-vax movement today, telling LBC radio that “the good news is that it’s not growing”.

“We monitor this very carefully and actually the number of people who want to have the vaccine is increasing,” he said

“The regulators are fiercely independent – they would not approve this if it wasn’t safe.”

800,000 doses of BNT162b have passed batch testing and should be ready within the next few days, and will be prioritised for elderly people in care homes and care home staff, followed by over-80s and health and care service workers.

The UK has ordered 40 million doses – enough for 20 million people – with several million doses expected to be available by year-end. Scottish leader Nicola Sturgeon said the first vaccines would be available in Scotland from Tuesday next week.

Twitter has also seen a debate about how the UK was able to become the first country in the world to approve the vaccine.

Hancock said the country was able to move quickly because of Brexit, but Raine emphasised in the press briefing that the approval was “made under provisions under European law which exist until January 1”.

The European Medicines Agency will meet on 29 December to decide if the safety and efficacy of Pfizer and BioNTech’s vaccine supports its approval.

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A history of Pfizer

Few companies embody the term ‘pharma giant’ as much as Pfizer. Here we take a look at the colourful history of one of the biggest drugmakers in the world.

Pfizer was founded in 1849 by two recent German immigrants to the USA, Charles Pfizer and Charles Erhart. Both in their mid-twenties, the two men set up what was initially a fine chemicals business in a Brooklyn factory, using a loan from Pfizer’s father as capital. The company’s first product, a palatable anti-parasitic drug, made to taste like toffee, united Pfizer’s skills as a chemist with Erhart’s training as a confectioner. It was a success, and set the pattern for the company’s future development.

Pfizer’s Tokyo building

The convulsion of the American Civil War, which broke out soon after in 1862, had as much of an impact on the nascent pharmaceutical industry as on American society in general. The “first industrial war” involved drug producers as much as weapons manufacturers. Like their competitor Squibb, the sudden need for enormous quantities of painkillers and antiseptics for the Union armies provided a great scope to expand production. By 1868, Pfizer’s revenues had doubled since the start of the war, and their product lines had expanded greatly.

After the war, Pfizer continued to focus on industrial chemicals as much as medicines, producing the citric acid needed for the emerging soft drinks industry, fuelling brands like Coca Cola and Dr Pepper’s expansion in the 1880s. This became their mainstay for many years, laying the basis for their continued growth. Also, when supply of tartaric acid was disrupted due to the civil war and increased tariffs, Pfizer developed its production to become the leading supplier of chemicals in the US.

“The ‘first industrial war’ involved drug producers as much as weapons manufacturers”

Erhart died in 1891, and Pfizer in 1906, leaving a company of around 200 employees in the hands of Emil Pfizer, who served as president until the 1940s, the last member of the Pfizer family to be involved in managing the company. Under his stewardship, Pfizer’s expertise in scientific production methods developed greatly. In 1919 their scientists pioneered mould fermentation production of citric acid from molasses, freeing their citric acid business from European citrus fruit supplies, which had been disrupted by the First World War. They developed a deep tank fermentation process, the principles of which would later be applied to the production of penicillin. As a consequence of Pfizer’s innovation, the price of citric acid tumbled over the succeeding decades, with the value of the chemical falling by 5/6ths in 20 years. In 1936 the company discovered a fermentation free method of producing vitamin C, which they rapidly expanded into vitamins B2 and B12 amongst others, rapidly becoming a leading vitamin producer – chemicals that were very novel at the time.

This expertise in fermentation and large-scale pharmaceutical production put Pfizer in good stead when in 1941 the US government appealed to the pharma industry for support in producing penicillin for the war effort. In an unprecedented collaboration, Pfizer worked with government scientists, the researchers such as Frederick Banting who had been working on the drug before the war, and a plethora of other players in the industry to markedly improve the efficiency of drug production, as they proudly state “most of the penicillin that [went] ashore with Allied force on D-Day [was] made by Pfizer”.

Antibiotics marked the transition to the modern Pfizer. Their follow-up to penicillin, Terramycin, first marketed in 1950, was both their first proprietary drug, and the first for which the company used sales reps, their soon to be formidable force of salesmen starting with just eight members.

Pfizer initiated its first major internationalisation at this stage, moving into nine new countries in 1951. It was at this time they set their site at Sandwich in the UK, initially just to finish processing compounds imported from America, but due to tariffs on imported products the company rapidly expanded the plant to accommodate producing medicines from scratch. Pfizer’s international expansion put great trust in their local staff compared to other organisations, recruiting nationals and giving them a great deal of autonomy.

“Lipitor…became the biggest-selling prescription medicine ever, earning Pfizer $12 billion a year in 2007, one quarter of its total sales”

The areas that Pfizer directed its research into expanded in these years as well. In 1952, it established its Agricultural Division, beginning its foray into animal health, and in 1953 acquired Roerig, a nutritional supplement specialist, which became incorporated as a division in its own right. By the 1960s, Pfizer were at their “most diversified point in [its] history” – in its own words, its interests “stretched from pills to perfume, and petrochemicals to pet products”.

Throughout the 60s and 70s the company continued to bring out new drugs, such as the broad spectrum antibiotic Vibramycin, and broadening its research base, reorganising its R&D operations in 1971 into a Central Research Division, and increasing spend on this area of the company from 5% to 15% of revenue. This attention to innovation began to pay off in the 1980s, with a series of blockbusters, the first of which, the COX inhibitor Feldene, arrived in 1980 rapidly becoming one of the biggest-selling anti-inflammatories in the world. Others rapidly followed, including Glucotrol, aimed at diabetics, and Procardia, an anti-hypertensive. The 1990s and 2000s would soon take this blockbuster-based success to new levels.

The statin Lipitor, approved in 1997 for Warner-Lambert before their merger with Pfizer, became the biggest-selling prescription medicine ever, earning Pfizer $12 billion a year in 2007, one quarter of its total sales. It almost hadn’t made it through clinical development, facing problems with ineffective chiral isomers and limited efficacy in animal testing, but showed such impact in human trials that it blew the competition away.

But Pfizer’s almost Hollywood-level blockbuster of the 1990s was the little blue pill of Viagrar. Formulated initially at the Sandwich site in the UK as an anti-hypertensive, it was found have “unexpected” side effects that made the company rapidly change the indication to erectile dysfunction. But despite the cultural ubiquity, Viagra has recently faced the inevitable threat from competition and generics, dropping from 92% of the ED market in 2000 to around 50% in 2007, with vigorous competition from drugs such as Cialis and Levitra.

“Pfizer is the 6th largest lobbier in Washington, and spent $25 million on lobbying during the passing of Obama’s healthcare reform legislation alone”

Ups and downs

Like most pharma companies of its size, Pfizer has faced its fair share of controversy as one of the most well-known drugmakers in the world.

In 2009, Pfizer faced more than $2 billion in legal settlement payments over marketing practices for drugs, and around the same time announced it would close a large number of manufacturing and R&D sites worldwide, including its Sandwich facility, which at the time employed 2,400 people (though it ended up maintaining a reduced presence at the site).

In the late 2000s/early 2010s, Pfizer, like many other big pharma companies, was experiencing pipeline difficulties too, with drugs accounting for 40% of its sales coming off patent, and a series of high-profile failures of drugs in development, such as the anti-cholesterol drug torcetrapib that caused a marked increase in deaths compared with the control group in clinical trials. The news of this disastrous result came days after CEO Jeff Kindler had hailed the drug as potentially “one of the most important compounds of our generation”. Likewise, tanezumab, an anti-osteoarthritic, failed in trials.

However, these challenges in the core mission of drug discovery led Pfizer to focus on other means of keeping up its dominant position. One thing that highlighted this changed focus was the appointment of Kindler as CEO in 2006. Kindler was trained as a lawyer, and was a relatively new employee when he was given the top job in preference to others of much longer standing with scientific experience, highlighting the increasing importance of legal and marketing issues over traditional R&D. He was succeeded by Ian Read and later Albert Bourla.

Perhaps unsurprisingly for the biggest company in one of the biggest industries in the world, Pfizer has also been proficient in exerting its considerable political influence to preserve its interests, coming in as the 6th largest lobbier in Washington, and spending $US 25 million on lobbying during the passing of Obama’s healthcare reform legislation alone. It has been key in pushing counterfeit drugs up the political agenda, in part due to its ownership of that most counterfeited of drugs, Viagra. It has also been highly critical of parallel trade, and has been one of those militating for a pharmaceutical repackaging ban in the EU.

Despite this political clout, the company also tried to belay its image as a pharma monster, like many others in the industry, by spending generously on charity, donating AIDS drugs both to poor communities in the US, and to developing countries.

The era of mega-mergers

Since the turn of the millennium, Pfizer has embarked on a series of mega-mergers, gobbling up Warner-Lambert in 2000, Pharmacia and Upjohn in 2002, Wyeth in 2009, and Medivation in 2016.

In 2015 the company also paid $17 billion to acquire Hospira, a firm specialising in injectable drugs and biosimilars, at a time when copycat biologics were starting to make real waves in the market. The deal seemed to be a precursor to Pfizer’s plans to separate its patent-protected medicines business from its off-patent portfolio.

These plans were soon abandoned and Hospira has remained a key part of the core Pfizer organisation – but that didn’t put the idea of separate business units to rest completely.

In 2017/2018 Pfizer attempted to sell its consumer health unit, but buyers including Proctor & Gamble and GSK pulled out of negotiations.

This caused Pfizer to change its tactics, and instead the company ended up signing a deal with GSK to combine the two companies’ consumer health businesses and form a joint venture with combined annual sales of $12.7 billion.

Pfizer and GSK plan to divest the business completely in the long term and reap the rewards, while merging the two businesses is also expected to create cost savings for both partners.

Similarly, in 2019 Pfizer announced a deal to merge its Upjohn generics business with Mylan, creating a combined company called Viatris. The $12 billion deal was cleared in November 2020, creating a generics behemoth with annual sales of around $19 to $20 billion and operations in 165 markets around the word.

This era, though, was also marked by two major failed acquisitions, which both courted controversy due to Pfizer’s intention to exploit tax loopholes.

In 2014 the company made an offer of around $100 billion to acquire UK firm AstraZeneca (which at the time was going through a rough patch).

AZ seemed to have little interest in the idea, and the deal was instantly controversial in both Europe and the US. The merger would have created the biggest pharmaceutical company in the world – and would have given Pfizer a way to avoid paying costly US taxes on foreign earnings (a stance that president Barack Obama criticised heavily).

Indeed, critics feared this redomiciling was the main aim of the merger, and that Pfizer wouldn’t sustain investment in UK R&D in the long term.

Unusually, the UK parliament ended up getting involved, perhaps underlining the importance of AZ to the country’s life sciences sector, with both AZ and Pfizer asked to argue for the future of the company in parliamentary hearings. Pfizer seemed unable to allay the concerns of prime minister David Cameron and business secretary Vince Cable.

After numerous “friendly bids” and just as many rejections, Pfizer eventually made a final offer of £69.3 billion ($118 billion) – which was also turned down by AZ, with the company saying it was “inadequate”.

Leif Johansson, AZ’s chairman, did not mince his words, saying: “Pfizer’s approach throughout its pursuit of AstraZeneca appears to have been fundamentally driven by the corporate financial benefits to its shareholders of cost savings and tax minimisation.

“From our first meeting in January to our latest discussion yesterday, and in the numerous phone calls in between, Pfizer has failed to make a compelling strategic, business or value case. The Board is firm in its conviction as to the appropriate terms to recommend to shareholders.”

This did not stymie Pfizer’s desire to move its HQ out of the US, though. The next year it also attempted a ‘reverse takeover’ of Irish Pharma firm Allergan – where, technically, Allergan would acquire the US company and rename itself as Pfizer, allowing Pfizer to have its tax base in Ireland.

At the time $160 billion deal was the biggest ever seen in the pharma sector.

But soon the Obama administration came down hard on such ‘tax inversion’ deals, changing laws such that the deal was no longer attractive to Pfizer.

No signs of slowing down

Despite some setbacks, Pfizer remains one of the biggest pharma companies in the world today. The sheer size of the organisation is mindboggling, totalling well over 100,000 employees. One commentator compared the company’s 38,000 sales reps to “three army divisions”, a sales team that has been immortalised in a Hollywood rom-com of all things – Love and Other Drugs, starring Jake Gyllenhaal and Anne Hathaway.

And with the company becoming one of the first in the world to get a COVID-19 vaccine approved – via its collaboration with  BioNTech – it feels like we’re only on the cusp of seeing where the company could head in the future.

Pfizer’s sheer diversity and economies of scale likely mean it will have the power to shape the pharmaceutical industry well into the 21st century. With fingers in every pie, ranging from small molecules to biologics in every clinical area, to stem cells and consumer goods, Pfizer will surely celebrate its 200th anniversary in as strong a position as it spent the last 160 years.

For all the latest Pfizer news follow pharmaphorum’s Pfizer tag.

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Pfizer/BioNTech to deliver COVID-19 vaccine to UK after approval

Pfizer and BioNTech are preparing to deliver their COVID-19 vaccine to the UK after the country’s drugs regulator became the first authority in the world to approve it.

As predicted by pharmaphorum, the regulator was able to move faster than its counterparts from the European Medicines Agency, who are also conducting a separate review of the data.

Pfizer and BioNTech have an agreement to supply the UK with 40 million doses of the vaccine, which is called BNT162b2 and was shown to be 95% effective in a phase 3 trial.

The companies said they will take immediate action to begin delivery of the vaccine and the first doses are expected to arrive in the country over the coming days, with the entire tranche expected to be complete next year.

Distribution will be prioritised – the Joint Committee on Vaccine and Immunisation has already set out priority groups who will receive the vaccine.

There are 11 groups, with older adults living in care homes and care home workers in the first group and those aged 80 years of age and older and health and social care workers second on the list

Delivery will begin throughout 2020 and 2021 to ensure fair allocation of the vaccines across different areas.

Another issue will be the logistical challenges of storing the RNA-based vaccine at around -70C and sending it out to clinics and GP surgeries across the country.

Danny Mortimer, chief executive of the NHS Confederation, which represents organisations across the healthcare sector, said there are still questions that need to be ironed out to support the delivery process.

Mortimer said: “This is the starting klaxon for people readying to deliver the vaccine. What’s ahead will be a marathon and not a sprint, with many months ahead to vaccinate everyone who needs it.

“This welcome news, however, does not mean that we are immediately out of the woods.

“Our already-stretched NHS faces a monumental effort now to roll-out the vaccine quickly and effectively.”

Nevertheless the UK health secretary Matt Hancock tweeted that “help is on its way” after the announcement.

Earlier this month the UK became the first country in Europe to pass 50,000 deaths from the coronavirus.

Transmission rates have fallen in the last month but only because of another economically crippling national lockdown, which has cost thousands of people their livelihoods as businesses struggled to survive.

Pfizer’s CEO Albert Bourla said: “As we anticipate further authorizations and approvals, we are focused on moving with the same level of urgency to safely supply a high-quality vaccine around the world. With thousands of people becoming infected, every day matters in the collective race to end this devastating pandemic.”

The MHRA is not the first national regulator to approve a coronavirus vaccine – that accolade goes to the Russian regulator, which backed the “Sputnik V” vaccine developed independently by a team in Moscow.

But this is the first approval based on phase 3 data as the Russian vaccine was only licensed on an interim basis after a review of earlier clinical data.

Other regulators are also reviewing the Pfizer/BioNTech vaccine, including the FDA, and the MHRA is also reviewing data rivals from Moderna and AstraZeneca/Oxford University.

Feature image © BioNTech SE 2020, all rights reserved

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AstraZeneca sells rights to cholesterol drug Crestor to Grunenthal

AstraZeneca is to sell European rights to its cholesterol drug Crestor (rosuvastatin) to Germany’s Grunenthal.

Crestor is a statin and at its peak generated annual revenues of more than $7 billion but it lost patent protection in the US four years ago and sales have tumbled.

Grunenthal will pay $320 million up front for rights to Crestor and associated medicines in over 30 countries in Europe, except for the UK and Spain.

The German pharma could also make milestone payments of up to $30 million and the deal is expected to be completed in the first quarter of 2021.

AZ will continue to manufacture and supply Crestor to Grunenthal during a transition period. AstraZeneca will also continue selling the medicine in other countries, including those in North America, Japan, China and other emerging markets.

AZ has a strategy of selling off its older drugs and reinvesting the proceeds in its research pipeline.

This has helped the company overcome one of the worst patent cliffs in the industry as Crestor and several other blockbusters encountered generic competition.

Income arising from the upfront and future payments will be reported in AstraZeneca’s financial statements within other operating income and expense.

The divestment will not impact the company’s financial guidance for 2020.

Ruud Dobber, executive vice president, BioPharmaceuticals Business Unit, said: “This agreement supports the management of our mature medicines to enable reinvestment into the pipeline and bringing new, innovative treatments to patients.

“Grunenthal previously acquired the rights to several established AstraZeneca medicines and is well placed to ensure continued access to Crestor for patients across Europe.”

Crestor is a lipid-lowering medicines and is used to treat blood disorders and to prevent cardiovascular events such as heart attacks and strokes.

It produces its lipid modifying effects in two ways: it blocks an enzyme in the liver causing the liver to make less cholesterol, and it increases the uptake and breakdown by the liver of cholesterol already in the blood.

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Moderna seeks COVID vaccine okay as data backs 94% efficacy

Moderna has said it will file for US, European and UK emergency approval of its coronavirus vaccine straight away, after reporting updated phase 3 results for the shot.

The primary analysis from the 30,000-subject COVE trial of mRNA-1273 – based on 196 confirmed cases of COVID-19 – has come in at 94% efficacy, with 185 cases in the placebo arm and just 11 among those given the vaccine after two months of follow-up.

The efficacy rate is almost identical to an earlier readout after 95 confirmed cases of COVID-19 in COVE, which is being run by the US National Institute of Allergy and Infectious Diseases (NIAID), and the safety profile also looks clean, according to Moderna.

It also appears to prevent volunteers from getting very sick from the virus, as all 30 cases of severe COVID-19, and single coronavirus-related death, were in the placebo arm.

The FDA and EMA will now look at the results and see if the mRNA-based vaccine can be given a green light for widespread use, and according to Moderna the data will be discussed at a meeting of its Vaccines and Related Biological Products Advisory Committee (VRBPAC) on 17 December.

Pfizer and BioNTech’s mRNA-based shot BNT162b was the first coronavirus vaccine to be submitted for emergency approval in the US on 20 November, but at the time of writing hadn’t yet been given a green light.

AstraZeneca and the University of Oxford’s adenoviral shot AZD1222 meanwhile has also been submitted for approval in Europe under the rolling review procedure, as well as in the UK. The company expects to file for approval in the US after the readout of a US trial in 40,000 patients that hasn’t yet generated results.

While AZD1222’s efficacy hasn’t matched the mRNA vaccines in trials so far, it will be cheaper and easier to distribute as it can be kept at standard refrigeration temperatures.

As it stands, the Pfizer/BioNTech shot has to be kept at -70 degrees Celsius – although the partners are testing stability at warmer temperatures – and Moderna has data suggesting its vaccine is stable for a month in standard refrigeration once taken out of a freezer.

AZD122 is expected to cost around $4 per dose, compared to approximately $20 for BNT162b and $32-plus for mRNA-1273.

Russia’s adenoviral shot Sputnik V meanwhile has a claimed efficacy of 92%, will cost less than $10 a dose, and can also be stored at standard fridge temperatures.

Moderna said that it will also seek prequalification and emergency use listing from the World Health Organization (WHO), which provide a route to market for vaccines, drugs and other healthcare products that meet pressing public health needs, particularly in low- and middle-income countries.

As with the other vaccine data readouts, there are still a lot of unanswered questions, including whether the shots can cut viral transmission rates – including asymptomatic transmission – how long protection may last, the impact on hospitalisation rates, and long-term safety.

“We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalisations and death,” commented Moderna’s chief executive Stéphane Bancel.

The US biotech has reiterated its expectation of having 20 million doses of mRNA-1273 available by the end of the year, which is earmarked to supply the US, which has ordered 100 million doses. 50 million doses are also due to head to Japan, and 20 million to Canada, while the UK has just raised its order to 7 million.

Shares of Moderna were up more than 16% on the Nasdaq as the markets opened in the US.

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UK appoints COVID-19 vaccine rollout minister as country preps for launch

The UK has appointed Nadhim Zahawi as vaccine rollout minister as the country prepares for a potential approval of Pfizer/BioNTech’s ground-breaking COVID-19 vaccine.

According to press reports, the UK’s drug regulator, the Medicines and Healthcare products Regulatory Authority (MHRA) could become one of the first bodies to approve the vaccine.

According to the Financial Times, the MHRA could approve the vaccine by 7th December after the companies announced supportive data from a phase 3 trial mid-way through November.

Nadhim Zahawi

Zahawi will therefore face the difficult task of overseeing distribution arrangements for the shot, which must be stored at around -70c during transit to retain its integrity.

A minister for business and industry, Zahari will temporarily relinquish responsibility for most of his duties at the Department for Business, Energy and Industrial Strategy (BEIS).

The interim arrangement will see the MP for Stratford-on-Avon serve as a joint minister between the BEIS and the Department for Health and Social Care.

The vaccines can only be kept in a fridge for up to five days before being administered, although Pfizer has designed a “pizza box” style transportation container.

The UK has ordered 40 million doses of the two-shot product, which could be up to 95% effective in preventing diseases, according to the companies’ top-line data.

Although the European Medicines Agency technically has authority to authorise medicines for the UK until December 31 under Brexit transition arrangements, the MHRA can temporarily authorise products in cases of urgent need.

The government has also written to the MHRA, asking it to use the same process to authorise the rival vaccine from AstraZeneca and Oxford University.

As reported by pharmaphorum, the MHRA’s forthcoming spilt from the EMA could potentially allow it to be more agile in its decision-making after Brexit.

Emergency approval is also expected in the US next week, the FT added, with shipments starting across the country within 24 hours of the announcement.

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EU fines Teva and Cephalon €60.5m for ‘pay for delay’ scheme

The European Union has fined Teva and its neurology unit Cephalon €60.5 million for an elaborate “pay for delay” scheme that prevented cheaper generic competition for its sleep disorder drug Provigil (modafinil). 

In a statement the EU said the scheme prevented generic competition for Provigil, which is used to treat narcolepsy, after its main patents expired.

The deal was agreed well before Teva bought Cephalon in 2011 for $6.8 billion and involved a complex series of transactions instead of an up-front payment.

Although Teva and Cephalon are now the same company, the case dates back to June 2005 when the firms were separate entities.

Teva introduced its generic modafinil product to the UK at half the price and Cephalon responded with an infringement lawsuit alleging infringement of its patents.

The two companies agreed to settle the dispute but as part of the settlement Teva received a package of commercial side-deals and cash payments.

In return the Israel-based pharma agreed not to compete against Cephalon and not to challenge its patents.

According to the European Commission and investigation showed that “the only reason Teva agreed to settle and not compete was that Cephalon offered to share the extra profits it would make by delaying entry”.

Cephalon also offered cash payments and side-deals to induce Teva into the settled agreement, the Commission said after an investigation that included evidence from internal documents.

Examples included a “lucrative” supply contact earning Teva at least five million euros in profits, even though Cephalon could cover its needs without the additional supplies.

The Commission said Cephalon also paid a significant amount for a licence to Teva’s own secondary patents, developed to pave the way to Teva’s generic entry.

However Cephalon did not see a need for, or decide to ever use, the licence.

Teva said in a statement: “The Commission started investigating this agreement in December 2009. Now, nearly 10 years later, the Commission issued a decision considering that the agreement infringed competition law.

“We are currently reviewing the decision but we continue to believe the modafinil patent settlement agreement did not infringe EU competition law in relation to the principles laid out by the ECJ.  We are planning to file an appeal before the General Court.”

 

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Vertex gets EU okay to treat younger cystic fibrosis patients

A new EMA approval has expanded the use of Vertex Pharma’s exon-skipping cystic fibrosis therapy Symkevi to children as young as six if they have specific gene mutations.

The regulator has given a green light to use of Symkevi (tezacaftor/ivacaftor) with Vertex’ Kalydeco (ivacaftor) in patients ages six years and older who have two copies of the F508del mutation in the CFTR gene, or one F508del copy and one of 14 other so-called “minimal function” mutations in CFTR.

The new EU approval comes after the FDA approved the expanded label last year, and provides the first treatment option that tackles the underlying cause of CF in patients aged six to 11 with these mutations.

Symkevi has been an option for CF patients in this group aged 12 or over for two years, but the new approval means treatment will now be able to begin much earlier. As CF is a progressive disease, that’s an important consideration for patients and their parents.

The combination will be made available immediately to qualifying patients in Germany, according to Vertex, and will be available shortly in the UK and other countries that have reimbursement agreements with the drugmaker, including Denmark and Ireland.

“Today’s approval brings us closer to our ultimate goal of providing medicines for all people with CF,” said Vertex’s chief executive Reshma Kewalramani.

Vertex introduced Kalydeco in 2012, and has since followed up with launches of two-drug combinations Orkambi (lumacaftor/ivacaftor) and Symkevi – known as Symdeko in the US – in 2015 and 2018, respectively. Together these drugs cover the CFTR mutations seen in around half of all CF patients.

The next phase of Vertex is focused on the roll-out of its new triple Kaftrio (tezacaftor, ivacaftor and elexacaftor), which was launched last year in the US (as Trikafta) and was approved by the European Commission in August.

Kaftrio covers a broader set of CFTR mutations spanning 90% of CF patients, but for now is only available for the 12 and up age bracket, according to its EMA-approved label.

NHS England agreed an access deal for the new drug earlier this year, although Vertex has agreed to submit real-world data on Orkambi, Symkevi and Kaftrio to cost-effectiveness agency NICE which means the drugs’ price could be adjusted.

Sales of the Trikafta/Kaftrio approached $1 billion in the third quarter, driving a 62% increase in revenues at the company even as even as Vertex’ older therapies started to decline.

CF is a rare, life-shortening genetic disease that affects the lungs, liver, gastrointestinal tract, sinuses, sweat glands, pancreas and reproductive tract. It is caused by a defective or missing CFTR gene, and there are around 75,000 people worldwide with the disease.

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UK’s Salient Bio launches robotic COVID-19 testing platform

UK diagnostics firm Salient Bio has launched a robotics-driven COVID-19 mass testing platform after spinning out from Imperial College.

The company says the technology is the fastest of its kind and can give results that are 99% accurate.

There are a range of approaches to mass testing – with one group even suggesting that a breath test could be used and is planning trials of the device known as Microtox BT.

Rapid tests are already being trialled at certain airports as a way of ensuring passengers boarding planes are not infected and unwittingly spreading the SARS-CoV-2 coronavirus that causes COVID-19.

A mass testing programme is also being trialled in the UK city of Liverpool, which has been badly affected by the virus.

London-based Salient was founded by former team members of Imperial College’s London BioFoundry, which handled the spin-out and accelerates commercialisation of synthetic biology research and technology.

With continuous testing vital for high human contact industries such as food preparation, factory work construction and education, Salient Bio says it allows COVID-secure environments at a quick cost effective rate.

It’s hoping to pick up clients in a range of sectors requiring regular human contact such as logistics, facilities management, education and manufacturing.

Despite promising vaccine developments, there will still be a lag as countries cope with the logistical challenge of vaccinating enough of the population – whilst developing countries will have limited access to vaccines owing to developed countries reserving 82% of the world’s supply of the Pfizer vaccine through 2021 and almost all Moderna vaccine supplies for the rest of 2020.

The platform is reagent agnostic, meaning that disruption in supply chains can be mitigated by a shift to different reagent suppliers without it calling for wholesale infrastructure change at Salient’s labs, therefore limiting disruption and costs.

This is an important factor when considering the existing fragility in supply chains caused by COVID’s disruption to logistics and the demand for continuous delivery of supplies for repeat testing at workplaces.

As the pandemic recedes next year, the platform could also be used for other diagnostic processes, according to Salient.

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Brexit could hinder access to coronavirus vaccines, says pharma group

The UK’s pharma industry trade body has warned that Brexit could derail the government’s efforts to get coronavirus vaccines to the population, but welcomed other measures in this week’s spending review aimed at reviving the economy after the pandemic.

In the build-up to chancellor Rishi Sunak’s announcement in the House of Commons, the Association of the British Pharmaceutical Industry (ABPI) chief executive Richard Torbett warned that a no-deal Brexit could disrupt supplies of vaccines.

He told Sky News that additional costs, bureaucracy and delays could follow a no-deal Brexit, or an agreement failing to address the complexity of drug regulation.

Brexit talks are on a knife edge as the transition period nears its end and the EU’s chief negotiator Michel Barnier has threated to pull out of negotiations in London this weekend unless the UK changes its stance on issues such as fishing and state aid.

Torbett said: “We are as prepared as we can possibly be, but we don’t need this extra red tape, extra complexity, extra cost and extra delay getting in the way of our supply chain at a time where we’re trying to deal with COVID.

“Clearly this is very frustrating and all of the time and effort and resource that has been put into the multiple levels of scenario planning around Brexit is time and effort and resource that could have been put to other better uses.”

The ABPI had better things to say about the spending review, however.

The industry welcomed £3 billion pledged to support the NHS from the impact of COVID-19 and noted a £14.6 billion funding boost to help the UK grow as a leader in science and technology.

Torbett said in a statement: “As the government focuses on its growth agenda, it should look to life sciences and make the most of this funding to unlock the future potential of our sector.

“Policies that encourage investment into cutting-edge research – such as delivering on the vision for UK health data – will deliver a triple win: for jobs, for the economy, and for the UK’s world-beating life sciences sector.”

Sunak also announced £6 billion in funding to pay for coronavirus vaccines, which is part of a package of measures designed to help the country recover from the pandemic worth £55 billion.

“As companies begin to seek approval from the regulator for new COVID-19 vaccines, it’s critical that we get the roll out right. Today’s funding will help them and the NHS plan for this enormous task and work together so that the right logistics are in place,” said Torbett.

The ABPI said it wants further plans including capital grants for medicines manufacturing, enhanced R&D tax credits, investment in preventive healthcare and modernisation of NICE appraisal methods to further stimulate the life sciences sector.

 

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The calm after the storm: How COVID-19 is making pharma more resilient

COVID-19 is proving to be the perfect storm in terms of the supply of pharmaceutical products. But learning how to overcome the challenges of 2020 will serve the industry well for years to come. As part of our EU Leader series, Christian Pawlu, head of strategy, portfolio and BD&L at Sandoz, told us about how securing supply in a time of crisis will ensure future access, build resilience, and transform relationships.

Since the start of the year, pharmaceutical companies have been riding a rollercoaster of challenges. Pawlu describes a “perfect storm” as the various strands came together to threaten supply chains.

“First, we saw a doubling or tripling of usual demand for a lot of our products. At the same point, there were big worries about supply chains in China.

“Then, as we went further into the crisis, there were some almost protectionist moves in some countries, as they placed or considered export bans on active pharmaceutical ingredients (API).”

Navigating this rapidly evolving landscape presented a challenge, but not an insurmountable one, Pawlu says.

“The industry, and our company in particular, always has business continuity plans in the drawer. But never in recent history have we had to pull out strategies for so many of our products and subsidiaries at the same time and put them into place.”

Daily calls with supply chain colleagues, activating second sources and alternative supply chains, along with strategic API and finished product stockpiling, all contributed to an absence of any major disruptions.

“For us, the crisis was also a reminder of our purpose as a company: to provide and pioneer access to the patient. We were the first company to commit to keeping prices stable for drugs seen as essential treatments for COVID-related symptoms.

“As an industry, we will have to be more honest with ourselves. We’ll be much better able to see where we have a really deliverable message and when we elicit a response, rather than measuring it by the time people spend with the customer”

“We made a commitment early on that we would not want to benefit from any shortages. In addition, we have made a commitment to provide 15 drugs to low-income countries at cost.”

Remote pharma

COVID-19 has fundamentally changed the way all sectors work on a day to day basis, but pharma did not have the luxury of time in allowing these changes to bed in.

Within a week, all 100,000 employees at Sandoz and parent company Novartis had transitioned from office to remote working, a process Pawlu describes as relatively “frictionless”.

“The biggest challenge was the interaction with our customers, because we weren’t able to see healthcare providers physically anymore. But, in the end, that turned out to be an opportunity.”

Before the pandemic, Sandoz was able to reach around 15% of its customers digitally, but that has now increased to around 70%.

As people adjusted to connecting digitally, through Zoom, Microsoft Teams, and other video-based software, in their private lives, this expanded into their professional lives, says Pawlu.

“Traditionally, the way we interact with our customers has been a big barrier to conveying messages, particularly in off-patent pharma.”

While using digital channels will not necessarily be easier, it will make companies think differently about how best to interact with healthcare professionals, Pawlu believes.

He says: “The key question we need to ask ourselves is, if we have more access to physicians, how do we want to use it? More reach? More efficiency?

“We are working through this as we speak and are thinking how we complement or even replace the traditional channels, and how we can reach customers we haven’t reached so far. It’s exciting.”

As the industry moves from a face-to-face to digital communication model, it needs a change of mindset, he adds.

“A physical person showing up in a physical office is the old normal.

“As an industry, we will have to be a bit more honest with ourselves. We’ll be much better able to see where we get access, where we have a really deliverable message, and when we elicit a response or an active request for follow up, rather than measuring it by the time people spend with the customer.”

Resilient future

Another change Pawlu hopes is here to stay is the increased communication and collaboration between industry and policy makers.

This is, in part, thanks to a greater appreciation of the importance of resilient supply chains, he says.

“Over the last 30 years, the volume of products produced in Europe versus Asia has flipped. The majority of APIs and an increasing share of FDF is currently being manufactured in Asia,” explains Pawlu, adding that this was driven, particularly in generics, by price.

“I think the balance we need to keep in mind is cost, quality, and resilient supply. You can optimise all three, but you can only maximise two at the same time.

“If you can go for the highest quality and resilient supply, you will have to pay a higher cost, or you do it the other way around – of course we never want to compromise on quality.”

Supply chain issues during the pandemic have brought this argument into sharp focus, and it is now “on the radar” at an international level.

“Sandoz has been in contact with heads of governments across Europe, and I’m extremely happy that this topic has gained so much attention,” he says, adding that the European Commission has committed to developing a continent-wide pharma strategy.

Back in July, Sandoz announced that it had entered a partnership with the Austrian government to keep production of penicillin at the company’s Kundl facility – the last remaining integrated production chain for antibiotics in the western world.

“Austria is something that’s been very visible, but we’re having similar discussions on other product areas with other governments,” Pawlu says.

Ultimately, 2020 has been a challenging time for pharma, but it has also presented a myriad of opportunities to learn and evolve.

For Pawlu, COVID-19 has highlighted how we transform the way the industry works – from manufacturing and supply chains, to sales and detailing – in a way that ensures everyone can access the high quality, affordable medicines they need to live happier, healthier lives.

About the interviewee

Christian PawluChristian Pawlu is the global head, strategy, portfolio and BD&L for Sandoz and a member of the global Sandoz Executive Committee. Christian studied medicine in Germany, Canada and France and is a licenced physician. Before he joined Sandoz, Christian was a start-up entrepreneur.  He was a partner at McKinsey & Company where he specialised in pharmaceuticals and medical products with a focus on generic drug manufacturers. Prior to joining McKinsey, Christian was a neuroscience researcher at the university of Freiburg, Germany. Christian is married to a professor of medicine and they have three children.

About the author

Paul TunnahDr Paul Tunnah founded pharmaphorum in 2009, which combines industry leading publications (www.pharmaphorum.com) with a specialist strategy and content marketing/communications consultancy (www.pharmaphorumconnect.com). He is a recognised author, speaker and industry advisor on content marketing, communications and digital innovation, having worked with many of the world’s leading pharmaceutical companies and the broader ecosystem of healthcare organisations.

In June 2020, he became chief content officer for Healthware Group, a next-generation integrated consulting group that operates at the intersection of the transformation of commercial operations and digital health, offering a unique range of services combining design, strategy, communication and innovation with technology and corporate venturing.

Connect with Dr Tunnah at https://www.linkedin.com/in/paultunnah/ or https://twitter.com/ptunnah

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FDA approves Alnylam’s ultra-rare disease drug Oxlumo

The FDA has approved Alnylam’s gene silencing drug Oxlumo, the first treatment for primary hyperoxaluria type 1 (PH1), an ultra-rare and life-threatening genetic disorder.

Oxlumo (lumasiran) was also approved in the European Union last week, making it the third from Alnylam’s pipeline of RNA interference therapeutics to make it to market.

The approval will mean that Alnylam has a clear run at this small but potentially profitable niche market, as the nearest rival from Dicerna is further back in the pipeline.

Patients with PH1 produce far too much oxalate, a substance consumed in food and produced by the body.

This combines with calcium to cause kidney stones and deposits in the kidney, which can lead to kidney failure and the need for dialysis.

As the kidney function worsens, oxalate can build up and damage other organs including the heart, bones and eyes.

The disease is also difficult to diagnose and often takes around six years before doctors correctly identify it.

Oxlumo works by targeting hydroxyacid oxidase 1 mRNA that codes for the enzyme glycolate oxidase.

Preventing the body from producing this enzyme has the knock-on effect of reducing the synthesis of oxalate.

There was no immediate announcement from Alnylam about pricing – but it’s likely to be eye-watering given the rarity of the condition.

Alnylam’s Givlaari, FDA-approved a year ago for acute hepatic porphyria, costs $575,000 per year at full price in the US, although after discounts the figure is more likely to be in the region of $442,000 per year.

In Europe, the company said it will reach separate pricing deals with each member state as quickly as possible.

Although the company has broken new ground with its technology, it is not yet profitable and saw its losses increase in Q3 to more than $253 million, worse than last year’s Q3 loss of $208.5 million.

Alnylam is hoping that revenue will stream from its new products and payments from Novartis, which owns the rights to cholesterol lowering drug inclisiran.

Alnylam licensed inclisiran to The Medicines Company, which was bought last year by Novartis for $9.7 billion.

The Swiss pharma’s bet looks to have paid off as inclisiran is likely to be approved in Europe in the coming weeks after backing from CHMP regulators last month.

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Regeneron’s COVID-19 antibody cocktail gets US emergency licence

Regeneron’s antibody cocktail is the latest COVID-19 drug to receive Emergency Use Authorization in the US, becoming the first therapy of this kind to become available.

The cocktail of casirivimab and imdevimab is still being investigated in trials but the FDA has enough data to grant a temporary licence while the pandemic continues.

Formerly known as REGN-COV2 or REGEN-COV2, the cocktail can be used for mild to moderate COVID-19 in adults and children at least 12 years of age and weighing at least 40 kg.

Doctors now have another option to choose from to combat the disease, following EUAs for drugs such as Eli Lilly’s baricitinib and Gilead’s Veklury (remdesivir).

To be eligible for Regeneron’s combination, patients must have received positive results of direct SARS-CoV-2 viral testing and be considered at high risk for progressing to severe COVID-19 and/or hospitalisation.

Clinical evidence from Regeneron’s outpatient trial suggests that monoclonal antibodies such as casirivimab and imdevimab have the greatest benefit when given early after diagnosis and in patients who have not yet mounted their own immune response or who have high viral load.

As part of the Operation Warp Speed project to rapidly develop therapies and vaccines against the disease, the US government and Regeneron a supply agreement for the cocktail, which was famously used to treat president Donald Trump after he became infected.

Regeneron will coordinate with state authorities to allocate the cocktail on a weekly basis, based on prevalence of the disease in each state.

The first 300 doses will be provided at no cost to patients, although hospitals and clinics may add their own fees.

AmerisourceBergen will be the first national distributor to begin delivering the therapy.

Earlier this month, Regeneron had to modify a trial protocol for the therapy after independent safety experts said it should not be given to high-risk patients after an undisclosed safety issue emerged in testing.

In late October, Eli Lilly said it wouldn’t resume a trial of its rival antibody therapy in hospitalised patients after National Institutes of Health researchers said it wouldn’t help.

AstraZeneca is developing a long-acting antibody therapy combination in the US and other countries to prevent infection happening and as a therapy for those already infected.

Regeneron’s antibodies were designed to combat SARS-CoV-02 using the company’s proprietary genetically modified mice, which have been engineered to have a human immune system.

The antibodies bind non-competitively to the virus’s spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen in the human population.

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Pfizer/BioNTech prep US COVID-19 vaccine launch after emergency filing

Pfizer and BioNTech have filed for emergency use of their COVID-19 vaccine candidate in the US, paving the way for a launch before year-end.

The announcement is no surprise as earlier this week, Pfizer’s CEO Albert Bourla said the company was preparing to file phase 3 data from the vaccine known as BNT162b2 with the FDA after gathering the required amount of safety data.

On the efficacy side, the filing will highlight a vaccine efficacy rate of 95% in a phase 3 study testing patients with and without previous infection with SARS-CoV-2.

There was also solicited safety data from a random subset of around 8,000 patients aged 18 or above and unsolicited safety data from around 38,000 trial participants.

Pfizer said the companies are ready to distribute the vaccine candidate “within hours” after authorisation, which should occur within the next month or so.

The FDA this week authorised Eli Lilly’s baricitinib, just over a month after the company announced supportive phase 3 data in COVID-19.

While the regulator has not given guidance on how long the review will take, expect a similar, if not quicker, timeline given the importance of a working vaccine in the effort against the pandemic.

The companies have already begun rolling submissions across the globe including in Australia, Canada, Chile, Europe, Japan and the UK, and plan to submit applications immediately to other regulatory agencies around the world.

Based on current projections the companies expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

Pfizer and BioNTech are also working with governments and health ministries around the world to set up delivery arrangements for the vaccine, which must be stored at around -70C to maintain its integrity.

According to reports Pfizer has already designed “pizza box” storage cases for the vaccine to help with this and will likely distribute them from several hubs in each country.

The companies said they had already built up expertise after delivering the vaccine to more than 150 clinical trial sites across the US, as well as Europe, Latin America, and South Africa.

The phase 3 clinical trial of BNT162b2, which is based on BioNTech’s proprietary mRNA technology, began on July 27 and has enrolled 43,661 participants to date, 41,135 of whom have received a second dose of the vaccine candidate or placebo as of 13 November, 2020.

It is one of 11 vaccines that are in phase 3 development, including contenders from Moderna, Novavax and AstraZeneca, according to the World Health Organization’s regularly updated tracker document.

Feature image courtesy of NIAID/Rocky Mountain Laboratories

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Lilly’s baricitinib granted US emergency use in COVID-19

Doctors in the US are to get another option to treat COVID-19 after the FDA granted an Emergency Use Authorization (EUA) for Eli Lilly’s baricitinib.

Baricitinib is the active ingredient in Lilly’s rheumatoid arthritis drug Olumiant and is the latest example of a drug being repurposed to combat COVID-19.

Most of the drugs attempt to tackle the inflammation that can cause complications in patients with severe disease.

While not all the attempts to get existing drugs to work in COVID-19 have been successful, the FDA said there is enough evidence to justify the emergency use for baricitinib in adults and children aged over two who are hospitalised with the disease and require oxygen therapy or invasive mechanical ventilation.

This temporary authorisation, which only applies during the COVID-19 crisis, is based on data from the Adaptive COVID-19 Treatment Trial (ACTT-2) conducted by the National Institute of Allergy and Infectious Diseases, part of the government funded National Institutes of Health.

Patients treated with baricitinib in combination with Gilead’s remdesivir had a significant reduction in median time to recovery from eight to seven days (12.5% improvement) compared to remdesivir.

The FDA’s decision came as the World Health Organization has advised against using Gilead’s Veklury (remdesivir) to treat hospitalised patients with COVID-19, no matter how severe their illness, after saying new evidence no longer supports its use.

The update is in contrast to the FDA, which has approved remdesivir to treat patients hospitalised with COVID-19 last month, after it was granted and Emergency Use Authorization earlier in the year.

But in the new guidance published in the BMJ, the WHO’s experts recommend against using remdesivir in non-severe, severe, or critical patients, citing weak evidence.

However the panel said there is strong evidence in favour of using corticosteroids in patients with severe or critical disease.

The latest guidance was produced using a systematic review of latest evidence.

According to the panel of experts who drew up the guideline, the evidence suggests that remdesivir has no important effect on mortality, need for mechanical intervention, time to clinical improvement and other outcomes.

The guidance was triggered by findings of the WHO’s SOLIDARITY trial last month, which reported results treating hospitalised COVID-19 patients with remdesivir, the steroid hydroxychloroquine, and the antiviral combination lopinavir-ritonavir.

Findings of SOLIDARITY diverged from evidence gathered in the US – last month data from the National Institutes of Health-backed ACTT-1 trial study showed Veklury resulted in five days’ faster recovery in patients hospitalised with COVID-19.

There was a non-statistically significant trend towards a reduction in mortality, with the effect being more pronounced in patients who were on low-flow oxygen at baseline.

In a statement, Gilead noted that Veklury has been included in guidelines from the NIH and Infectious Diseases Society of America, as well as in national guidelines in Japan, the UK, and Germany.

Gilead added: “These recommendations are based on the robust evidence from multiple randomised, controlled studies published in peer-reviewed journals that demonstrate the clinical benefits of Veklury, such as significantly faster recovery, which can free up limited hospital resources.

“We are disappointed the WHO guidelines appear to ignore this evidence at a time when cases are dramatically increasing around the world and doctors are relying on Veklury as the first and only approved antiviral treatment for patients with COVID-19 in approximately 50 countries.”

 

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Gene Therapy Medical Affairs

The inaugural Gene Therapy Medical Affairs Summit is dedicated to exploring the pivotal internal and external role that Medical Affairs plays in delivering gene therapies to patients.

Industry pioneers from leading pharma and biotech companies at various stages of development and commercialization including Novartis Gene TherapyOrchard Therapeutics & Bluebird Bio will share how to engage effectively with internal clinical and commercial teams as well as external HCPs, regulators and patient advocates to create a cohesive and streamlined launch strategy for complex, high priced gene therapy products and ultimately work to remove both barriers that exist for access to gene therapies.

Join this definitive, niche conference to delve into the unique Medical Affairs challenges encountered when working with gene therapies, from adapting to the clinical realities of the rare disease space to handling long-term follow up and post-launch scrutiny, equipping you with the insights required to launch gene therapy products more efficiently and effectively than ever before.

This virtual event is set to be a highly interactive and engaging meeting. We fully understand (and quite frankly agree) that a presentation-heavy conference just isn’t up to scratch! As such we have created a new format for this meeting which maximises opportunities for engagement, discussion, and Q&A’s in order for you to get the best value from this meeting.

Access the official agenda for more information.

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NICE says yes to Braftovi combination for colorectal cancer

Two months after rejecting Pierre Fabre’s Braftovi for a rare form of metastatic colorectal cancer (mCRC), NICE has changed its mind, and now says the drug can be funded by the NHS in England, Wales and Northern Ireland.

The cost-effectiveness agency has backed the combination of Braftovi (encorafenib) and Eli Lilly’s Erbitux (cetuximab) as a second-line treatment option for BRAF V600E mutated mCRC after an improved access deal – which generally means a discount on its list price.

The pairing of the BRAF inhibitor and anti-EGFR antibody was approved by the EMA in June on the back of the BEACON CRC trial, which showed a median overall survival of 9.3 months for the two-drug regimen and 5.9 months for patients in the control group, who received standard second-line chemotherapy. The duo also reduced the risk of death by more than a third (39%) compared to the control arm.

The green light made it the first and only targeted, chemo-free regimen licensed in Europe specifically for patients with BRAF V600E-positive mCRC, and came shortly after the combination was approved by the FDA for the same indication.

NICE turned down Braftovi/Erbitux in September, acknowledging the clinical benefits of the regimen but saying it was too expensive.

The agency also said the comparative chemo regimens used in BEACON CRC weren’t generally used in NHS clinical practice, so it was forced to rely on unreliable indirect comparisons in its modelling.

At the time, patient organisation Bowel Cancer UK said the decision was a big disappointment, as “treatment options for the one in ten people diagnosed with bowel cancer who have a BRAF V600E mutation are currently extremely limited.”

The charity’s chief executive – Genevieve Edwards – welcomed the change of heart by NICE. “We worked closely with clinicians to submit evidence to the NICE consultation on the benefits of the combined therapy, and are really pleased that today’s announcement offers new hope to patients,” she said.

In the UK, over 42,000 people are newly diagnosed with colorectal cancer each year, and around a quarter have tumours that have already metastasised to other parts of the body at diagnosis.

BRAF mutations are thought to occur in approximately 8% to 12% of patients with mCRC, and are associated with a poor prognosis.

“Conventional cytotoxic chemotherapy is associated with suppression of the immune system in many ways, and so this chemotherapy-free option is particularly pertinent in the current COVID-19 climate,” said BEACON CRC investigator Dr Harpreet Wasan.

“Historically, these patients generally have worse outcomes and a poor prognosis, when treated with standard, cytotoxic chemotherapy,” he added. “Today’s recommendation offers a significantly better option in their disease management.”

BEACON CRC also included another three drug arm – Braftovi, Erbitux, and MEK inhibitor Mektovi (binimetinib) from Array Biopharma (now part of Pfizer). That wasn’t able to improve survival any more than the two-drug arm however so wasn’t submitted for approval.

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FDA begins review of Samsung Bioepis/Biogen’s Lucentis biosimilar

Novartis/Genentech’s eye drug Lucentis could be the next big blockbuster to face competition from cheaper biosimilars after its US patent expired this year – and Samsung Bioepis and Biogen are closing in after the FDA accepted a filing for their cut-price rival.

Lucentis (ranibizumab) was first FDA approved in 2006 for wet age-related macular degeneration (wet AMD) and has picked up approvals in related eye conditions ever since, although its patent expired in June.

But it has been a source of controversy – it works by attacking the rogue blood vessels that build up in the retina that are the root cause of wet AMD, something that Roche’s Avastin (bevacizumab) cancer drug can do in an off-label use at a fraction of the price.

Because Roche has never applied for Avastin to be used in wet AMD, clinics in the US have had to choose between the peace of mind offered by the regulatory process and Lucentis’ higher price tag, or the unapproved off-label formulation of Avastin at a lower price.

Samsung Bioepis and Biogen are among a gang of biosimilar developers who want to change this situation and the FDA has just accepted a filing for their potential contender known as SB11.

The European Medicines Agency already began its review of SB11 last month and if approved it will be added to a portfolio of other drugs already marketed by Samsung Bioepis.

Samsung Bioepis, a joint venture between the Korean tech firm and Biogen, last year struck a new marketing agreement with Biogen for two ophthalmology biosimilar candidates, SB11 (ranibizumab) and SB15 (aflibercept), in the US, Canada, Europe, Japan and Australia.

Other potential Lucentis biosimilars could come from Hospira and Pfizer or Formycon/Bioeq, who have potential biosimilars nearing the end of clinical development.

Biosimilars are near-copies of complex biologic drugs grown in cells, that have been rigorously analysed and tested in trials showing that they have the same safety and efficacy profile as the originator drug.

Because the approval process is more complicated and the products themselves are expensive to produce, biosimilars are not sold at the rock-bottom prices of generics.

But they are still sold at a considerable discount compared with the originators and could save billions of dollars in healthcare costs in the coming years.

 

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COVID-19: Helping to support momentum on antimicrobial innovation

To mark World Antimicrobial Awareness Week NovaBiotics’s Deborah O’Neil tells us why 2021 might be the year anti-infective drugs finally demonstrate their economic value. 

COVID-19 has reminded the world how critical infectious disease is, from both a societal and economic standpoint. Cancer is rightly seen as one of the most pressing challenges of our time: but it has not yet caused a multi-trillion hole in the world’s finances.

For the first time in my career developing antimicrobials, I’m hearing more investors enthused by the prospect of investing in companies developing solutions to infectious diseases. We all know COVID-19 has shifted our perspective on a range of things, and in economic terms three developments have underpinned this shift.

First, there is now a wealth of innovation, perhaps more than ever, in antimicrobial design and development (almost all of it being generated by SME businesses). Second, push incentives from government and NGO bodies, particularly the AMR Action Fund, providing $1 billion of investment, are now substantial enough to really fuel that innovation. And third, pull incentives are now in place which are beginning to make an effective commercial case for antimicrobial development.

The NHS/NICE antibiotic subscription model announced earlier this year is potentially the most significant of these developments. The US PASTEUR Act, if enacted, would also pave the way for providing prepaid subscription contracts for antimicrobials in the US, collectively making antimicrobials viable again. Similar subscription models and other market entry reward proposals are being floated in Sweden and elsewhere.

After years of lobbying by the industry, policymakers now accept the need for “pull” models that de-link sales (by volume) from reward; reward being for developing and launching these drugs for when they are needed, not for promoting use. Antimicrobial stewardship is now clearly linked with economic success.

We’ve all heard the bear cases for antibiotics: the bankruptcy of Achaogen, fire sale of Tetraphase and other high-profile problems at antibiotic developers have highlighted the fact that even with the best possible support in the development phase, generating profitable versions of the ‘traditional’ antibiotic classes remains challenging. The decision by Cipla to withdraw Zemdri (plazomicin) from European marketing authorisation, is a sobering reminder that even highly effective antibiotics with proven efficacy are often not considered economically viable.

“We need to keep up the momentum. Although welcome, the pull incentives are the first small steps to creating the economic climate required for very successful commercialisation of antimicrobials.”

But now, just as a communicable disease poses the biggest economic challenge the world has faced in a decade, there are signs that new reimbursement models, alongside a new generation of innovation in development, have changed the rules of engagement.

Innovative and commercial savvy companies are creating platform technologies and diversified portfolios, focusing not only on antibiotics but desperately needed antifungals and antivirals as well.

NovaBiotics is proud to be developing antifungal and antiviral therapies alongside antibacterials, all of which mitigate resistance as they are based on platforms engineered from innate immune effector molecules – harnessing the way the body fights disease versus ‘synthetic’ approaches that introduce new resistance pressure to microbes. We are not alone in developing drugs which are designed to avoid creating antimicrobial resistance.

There’s every reason to believe that by the time these new drugs reach the marketing approval and launch, the reimbursement and commercial landscape will allow for a good economic runway.

We need to keep up the momentum. Although welcome, the pull incentives are the first small steps to creating the economic climate required for very successful commercialisation of antimicrobials. The forthcoming EU Pharmaceutical Strategy can perhaps create conditions to address market failure in antimicrobials and reinvigorate innovation, by taking the right actions. These include support for the SME companies which generate the lion’s share of innovation, better alignment between health systems and drug developers, the targeted use of diagnostics and a regulatory framework based around non-inferiority trials, to name a few.

The UK government, which has already played a leading role in creating a significant pull incentive for developers, is talking about creating an equivalent to DARPA. The UK has some of the world’s most innovative antimicrobial developers so there’s a clear incentive to do this.

This year may be the great awakening of the value of anti-infectives from a social perspective. 2021 could be the year that they demonstrate their economic case. Let’s use Antimicrobial Awareness Week to get that message out.

About the author

Deborah O’Neil is CEO and CSO of NovaBiotics.

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NICE backs Lilly’s Emgality for migraine, adding pressure on Novartis rival

UK cost-effectiveness agency NICE has said that Eli Lilly’s Emgality can be made available through the NHS for migraine prevention, the second drug in the CGRP inhibitor class to achieve that milestone.

The decision means that with two CGRP antibodies now cleared for migraine prevention, the first drug in the class to be approved in Europe – Novartis’ Aimovig (erenumab) – has fallen further behind its rivals in getting access to the UK market.

NICE has backed Emgality (galcanezumab) as a once-monthly injection to prevent migraine attacks in people with episodic or chronic migraine who suffer at least four days with a migraine headache per month, and who have tried at least three prior preventative medicines.

That puts Emgality ahead of Teva’s Ajovy (fremanezumab), which picked up a positive opinion from NICE earlier this year but is only recommended for use in chronic migraine sufferers who have 15 or more headache days a month for more than three months, with at least eight of those having features of migraine.

It also puts Lilly’s drug ahead of Aimovig, which has been rejected twice by NICE although the agency has agreed to take another look at the application after an appeals panel ruled that its technology appraisal committee had failed to consider all of the evidence about the cost-effectiveness for the drug.

NICE said Ajovy was an option for around 10,000 people in the UK in guidance issued in June, but Lilly says many more patients are eligible for its drug – around 144,000 people with episodic migraine and 59,000 people with chronic migraine.

The decision is based on trials comparing Emgality with placebo which showed that the antibody halved the number of monthly migraine headache days for up to 40% of adults with migraine who had previously tried three or more prior medicines, such as Allergan’s Botox (botulinum toxin type A) or topiramate.

Gemma Jolly of medical charity the Migraine Trust said NICE’s recommendation is “wonderful news for people living with this very painful and debilitating neurological condition [as] both chronic and episodic migraine patients across England and Wales will be able to access an effective drug on the NHS.”

The CGRP inhibitors have performed well in clinical trials, but so far commercial success has been limited, despite blockbuster sales predictions ahead of their approval.

First-to-market Aimovig generated sales of $108 million in the first nine months of 2020 for Novartis, which records ex-US sales, while Amgen booked $274 million from the drug in the US in the same period.

Aimovig is said to be the most prescribed anti-CGRP drug worldwide with more than 480,000 patients prescribed the drug worldwide. In the same period, Lilly reported sales of $253 million for Emgality, and Teva made $98 million from Ajovy.

Novartis is hoping for a bounce to Aimovig sales from the HER-MES trial reported earlier this month, which showed it was more effective than topiramate – a go-to oral therapy for people with chronic migraine – in a head-to-head trial.

There’s more competition jostling for position however, following the approval of Lundbeck’s Vyepti (eptinezumab), an intravenous drug that only needs to be administered four times a year.

Lilly has a real opportunity to build momentum behind Emgality in England and Wales, but will have to wait until next year before it hears from NICE’s counterpart in Scotland, the Scottish Medicines Consortium (SMC). Aimovig was cleared for use by NHS Scotland last year, with Ajovy given a green light in January 2020.

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Pfizer begins US pilot delivery programme for COVID-19 vaccine

Pfizer has begun a pilot delivery programme in the US for its experimental COVID-19 vaccine, as the company seeks to overcome logistical challenges caused by its ultra-cold storage requirements.

The vaccine developed in partnership with Germany’s BioNTech has been shown to be 90% effective in clinical trials.

But it has a major drawback in that it must be shipped and stored at around -70C, unlike conventional vaccines that are stored at standard refrigerator temperatures.

The company has picked four US states – Rhode Island, Texas, New Mexico and Tennessee, to trial a delivery programme that aims to overcome this challenge.

Pfizer told Reuters in a statement: “We are hopeful that results from this vaccine delivery pilot will serve as the model for other US states and international governments, as they prepare to implement effective COVID-19 vaccine programmes.”

The four states will not receive the vaccine earlier because of the pilot, according to Pfizer.

Pfizer is poised to file the vaccine with the FDA in the coming days, seeking an Emergency Use Authorization (EUA) after gathering enough safety data required by the regulator.

It was the first company to announce top-line phase 3 results showing that its vaccine is effective last week.

Pfizer and BioNTech have a $1.95 billion deal to supply 100 million doses of the vaccine to the US government, which has an option to acquire up to 500 million additional doses.

There are 11 potential COVID vaccines in late-stage clinical development and since Pfizer’s announcement two more groups from Russia’s Gamaleya Research Institute and US biotech Moderna have published favourable efficacy results.

Both Pfizer and Moderna vaccines use synthetic messenger RNA to activate the immune system against the virus.

They both code for the “Spike” protein seen on the surface of the SARS-CoV-2 coronavirus, which causes the body to produce antibodies that neutralise the virus in the event of an infection.

Feature image courtesy of Rocky Mountain Laboratories/NIH

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Vertex Pharma’s vision for reimbursement innovation

As regional vice president for Northern Europe & Australia, Simon Lem led the digital launch of Vertex Pharma’s novel cystic fibrosis drug Kaftrio. He tells pharmaphorum about embracing digital change and the need for innovative reimbursement solutions.

For Vertex, COVID-19 accelerated a digital transformation much needed for the patients they serve.

As the leading developer of novel drugs to treat cystic fibrosis (CF) the Boston-based company has always taken a very focused approach.

“For CF, you have a proportion of the population predominantly quite young and tech-savvy. They do not want to be coming into the hospital,” Lem tells pharmaphorum. “There was already a direction of the clinical community to be having these interactions or helping patients manage their disease virtually. COVID-19 sped up all of that.”

With COVID-19 posing an added risk to people with CF, Vertex was “even more motivated” to secure its supply chain and access to drugs. In June 2020, NHS England swiftly approved a reimbursement deal for Vertex’s fourth CF drug Kaftrio meaning the medicine would be accessible for doctors and eligible patients in England from the day (in August 2020) it received licensing from the European Commission, with the medicine being accessible by eligible patients in Scotland, Wales and Northern Ireland soon after. The drug has since launched digitally.

“I never thought that in my career, I would see a launch of a significant product without having a face to face interaction with a customer, but it has worked. Early results are positive, it hasn’t changed the mission,” says Lem.

Like other pharmaceutical companies, Vertex still faces challenges with reimbursement and market access. The agreement for Kaftrio followed a long battle with NHS England to make the company’s three other cystic fibrosis medicines available.

“It’s one thing if you can develop an innovative medicine, but then you’ve got to get it to patients for it to be useful… that is challenging for many healthcare systems.”

“The challenge we face is universal to any biotech company. You are operating in multiple different countries with multiple different healthcare systems, multiple different cultures and all the different ways they approach, reimbursement, or engagement,” explains Lem.

“It’s one thing if you can develop an innovative medicine, but then you’ve got to get it to patients for it to be very useful and I think that is challenging for many healthcare systems, particularly ex-US where you have finite and limited budgets. You also have very well-established long-term health technology, appraisal systems.”

The speedy nature of Kaftrio’s approval is encouraging for how reimbursement could look in the future, says Lem. Working flexibly with NHS England and NICE, Vertex managed to ensure patients got access to the drug on the day of licensing.

“I don’t know of many examples where that’s happened before if any, but primarily it was about taking a step back and asking what we had learned from our ongoing discussions and how we could bring those forward into the next step of the negotiations.”

Engaging with the health system as early as possible and working flexibly was key to the success, he adds. “It has to be more collaborative. Especially if you move into things like gene therapies.”

UK’s opportunity for change

The UK government also has an opportunity now to speed up the process, Lem says. “I think sometimes other healthcare systems have looked at the UK as the ones that are playing catch up, and there is a less flexibility to change, but I think the UK could lead the way with this. We saw with our CF medicines; they can do it if all parties are motivated to do it.”

A more flexible approval process would also benefit patients within the UK. “Sometimes patients in the UK only get access to medicines much later than other European countries.  I think there needs to be innovation, flexibility, and open communication with all parties involved in in the process including the HTA system and the health authorities.”

A bigger challenge for healthcare systems in future will be deciding reimbursement for curative medicines. “We’re at a very embryonic stage across the pharmaceutical industry. There’s going to have to be even more collaboration, even more flexibility and even more talking at a far earlier stage than we’ve done previously.”

Starting his pharma career as a sales rep, Lem has worked across the industry in management and marketing roles. He notes how business practice has changed significantly over the years. “Now we are far more focused on individual patients and individual prescribers and that has changed how you go about doing the businesses. It is far more personalised, and that’s down from a key account manager’s perspective to even reimbursement.”

Diversifying focus

Vertex’s focus for now is on being less of “a one-franchise organisation” and diversifying its portfolio. The company is investigating new medicines for serious diseases with key unmet needs.

“We want to treat the underlying cause of the disease,” says Lem. “It will be interesting seeing how that pipeline pans out and the impact that that will have on the business.”

Expanding into new diseases areas will require a different approach from the organisation, says Lem, but presents an exciting new challenge. Having worked at Vertex for nine years, he says that no day is the same as the day before.

“I can tell you what I am doing today is not the same as what I was doing this time last year. I think it’s a really exciting journey because we’re doing stuff so rapidly and having such a big impact that and we go into new disease areas.”

However, the goal to find a cure for CF remains core to the company.

“People say to me, ‘Are you happy? Patients have got the medicines. It’s over and done with.’ I say, no, it is not – there is still a lot of work to do for CF. We brought four medicines to the market. Yet there’s still work to be done.

“We’ve got medicines with the potential to treat up to 90% of people with CF, but the other 10% still don’t have a medicine. Until that 10% have got a medicine, the game’s not over.”

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Guido Rasi steps down, handing the running of EMA to Emer Cooke

EMA executive director Guido Rasi has ended his second term at the helm of the EU medicines regulator, with Emer Cooke taking the wheel and becoming the first women in the role.

Rasi’s second five-year term came to an end on Friday (13 November), with his second stint dominated by the move of the EMA offices from London to Amsterdam – and the associated staff losses and ongoing disruption that has resulted from the UK’s withdrawal from the EU – as well as the pandemic.

Cooke will take over the EMA as the regulator is in the midst of handling the review and authorisation of medicines for COVID-19, including the first vaccines for the coronavirus, and as the regulator continues to work out its future relationship with the UK Medicines and healthcare products Regulatory Agency (MHRA) – which has been a big contributor to its expertise and workload.

Under Rasi, the EMA implemented a suite of reforms including a drive towards transparency – for example making clinical study reports (CSRs) publicly available – and the implementation of sweeping EU directives on pharmacovigilance, clinical trials and falsified medicines.

During his tenure the EMA also implemented new rules to encourage the development of advanced therapy medicinal products (ATMPs) like gene and cell therapies, and the introduction of the PRIME fast-track review for promising medicines.

Emer Cooke

Cooke is returning to the EMA after a four-year period as head of medicines regulation at the World Health Organization (WHO). She first joined the EMA in 2002 and filled a number of senior roles at the regulator including head of inspections, head of international liaison and head of international affairs before switching to the WHO in 2016.

A pharmacist by training, Cooke has also worked in the pharma industry and at European industry group EFPIA, and according to Rasi is “a strong leader who is committed to steering EMA during this very challenging period and ensuring that the agency’s work on COVID-19-related activities continues uninterrupted.”

In his final message as head of the EMA, Rasi said the number of COVID-19 drugs and vaccines being developed by pharma companies is “encouraging,” and pointing to the agency’s pivotal role “in reviewing the available data packages to ensure that our usual high standards of safety, efficacy and quality are achieved and upheld.”

Cooke meanwhile told Bloomberg that one of the biggest challenges she will face immediately after re-joining the EMA will be monitoring the safety of COVID-19 vaccines, particularly those that are based on new technologies like mRNA.

She also told the newswire that the EMA is adopting a different stance on gauging the efficacy of COVID-19 vaccines from the FDA, which has placed a 50% reduction in disease severity as its threshold for approval, saying guidance on its position will be published soon.

The EMA has already started reviews of Pfizer/BioNTech’s mRNA-based shot BNT162b2 and AstraZeneca/University of Oxford’s adenoviral-based candidate AZD1222.

Rasi’s first five-year term as executive director of the EMA was interrupted in 2014 when his appointment was prematurely annulled by European Union Civil Service Tribunal – on the grounds that the selection process for the post was flawed – only to resume his duties a year later.

Prior to the EMA role, Rasi was director-general of the Italian Medicines Agency from 2008, and previously spent three years as director of the Institute of Molecular Medicine in Rome.

“I am leaving EMA at a time when its mandate is set to be expanded. This is an acknowledgement of the good work and reputation that the agency has built over the last 25 years,” he said.

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Hungary steps out of line with EU to order Russia’s COVID-19 vaccine

Hungary is to order a consignment of Russia’s Sputnik V COVID-19 vaccine, as the country struggles to contain the infection rate.

According to press reports, the decision puts Hungary on “collision course” with the EU, which has not approved the vaccine or plans to review it either.

The European Medicines Agency has announced rolling reviews of vaccines from mainstream pharma companies including Pfizer/BioNTech and AstraZeneca, which allow regulators to review data in real time, allowing them to reach a conclusion quickly.

Minister of foreign affairs and trade Peter Szijjarto has been in talks with Russia, China and Israel in order to obtain early supplies of a vaccine.

Hungary’s prime minister Viktor Orban has warned that the country’s health service could be overwhelmed if the infection rate is not brought under control.

The decision from Orban is the latest example of the country stepping out of line with the rest of the EU, which is abiding by guidance issued by the EMA.

Earlier this week Russia claimed that Sputnik V was 92% effective, based on interim data from a study in involving 40,000 subjects.

The results would put it on a par with a vaccine developed by Pfizer/BioNTech, which has shown efficacy of more than 90% and no serious safety issues in more than 43,500 subjects.

The preliminary assessment is based on 20 COVID-19 cases split between the vaccinated and placebo arms of the study at 21 days, according to a press statement issued by the Gamaleya Institute which developed the vaccine and the Russian Direct Investment Fund (RDIF).

They said the positive interim results will be followed by “mass vaccination in Russia against COVID-19 in the coming weeks.” The country has had more than 1.8 million confirmed COVID-19 infections, and just over 31,000 deaths.

The readout from the study comes at a point when 20,000 people have been given the first of the two-dose regimen for the adenovirus-based vaccine, and 16,000 have had the second. There were no unexpected adverse events as yet, with most side effects injection site reactions or minor flu-like symptoms.

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Janssen combines Darzalex with COVID drug in new multiple myeloma submission

Janssen has submitted a new combination regimen for its blockbuster multiple myeloma drug Darzalex for approval with the FDA and EMA, hoping to give the treatment another edge over emerging competitors.

Specifically, the combination utilises the subcutaneous formulation of the drug, Darzalex Faspro (daratumumab/hyaluronidase) with Celgene’s multiple myeloma drug Imnovid (pomalidomide) and dexamethasone – which has gained new fame this year as one of the few treatments available for COVID-19.

Darzalex Faspro was approved earlier this year and cuts the drug’s dosing time to just a few minutes from hours.

Janssen is seeking approval for use in the treatment of patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. 

The submission is supported by data from the phase 3 APOLLO study, which showed significantly longer progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma who received the combination compared with pomalidomide and dexamethasone alone. 

Analysts think the shorter treatment of Darzalex Faspro time could become a particularly important advantage over the established formulation during the coronavirus pandemic, when getting access to healthcare has become more difficult under lockdown, and this combination could further boost the drug’s profile.

In September Janssen also submitted the formulation for approval in the rare and potentially fatal disease light chain amyloidosis.

The original IV version of Darzalex has been a big earner for J&J ever since it was first approved in 2015 as a fourth-line myeloma therapy, growing rapidly on the back of successive approvals in earlier lines of therapy – including most recently in newly-diagnosed patients.

The product brought in almost $3 billion in sales last year, and shows no signs of slowing down, growing another 49% to reach $937 million in the first three months of 2020. J&J licensed the drug from Danish biotech Genmab in 2012 in a deal valued at $1.1 billion.

Last month however saw the approval of its first direct competitor – Sanofi’s anti-CD38 antibody Sarclisa (isatuximab) – which was given the nod by the FDA as a third-line therapy for myeloma.

Sanofi’s drug is delivered intravenously and – according to Sanofi – has simpler, two-hour dosing that improves on the current Darzalex formulation, although analysts think the availability of J&J’s new subcutaneous version will likely cancel out that advantage.

Last year, J&J licensed a follow-up to Darzalex from Genmab, HexaBody-CD38, that it says could be used in Darzalex-resistant patients as well as in other cancer indications beyond myeloma, in the hope of extending its anti-CD38 franchise.

 

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EU orders 300 million doses of BioNTech/Pfizer’s COVID-19 vaccine

The European Union has ordered 300 million doses of BioNTech/Pfizer’s COVID-19 vaccine following this week’s landmark announcement that it was effective in more than 90% of patients.

The companies said deliveries of an initial order of 200 million vaccines will be subject to approval by European regulators and are expected to start by the end of this year. There is an option for a further 100 million doses.

The vaccine supply for the EU will be produced by BioNTech’s manufacturing sites in Germany and Pfizer’s manufacturing site in Belgium and based on current projections, the companies expect to produce globally up to 1.3 billion doses in 2021.

Regulators sitting on the European Medicines Agency’s CHMP scientific committee have already begun a rolling review of the vaccine, which will accelerate the process as they will be able to study trial results as they are made available.

Vaccine doses for Europe will be produced in BioNTech’s German manufacturing sites, as well as in Pfizer’s manufacturing site in Belgium. If the BNT162b2 vaccine candidate receives approval from the European Medicines Agency (EMA), then doses will be ordered by the EU Member States who have elected to receive the vaccine as part of this agreement.

The Pfizer/BioNTech vaccine is based on mRNA, which instructs the body to produce the “Spike” protein on the surface of the SARS-CoV-2 coronavirus that causes COVID-19.

It does have one practical drawback as it must be stored at around -70C until the day it is used and there are already concerns this may make large scale vaccination schemes difficult.

The Independent reported that AstraZeneca’s rival vaccine, which is based on a viral vector and is also nearing the end of clinical development, could be easier to work with.

The AZ vaccine can be stored at fridge temperature, although there have been concerns about its safety after a late stage clinical trial was put on hold at the beginning of last month before resuming.

While Pfizer was keen to take the plaudits for developing a vaccine at speed from a standing start at the beginning of the year, it also faced uncomfortable questions about the conduct of its CEO Alfred Bourla.

It emerged that Bourla sold shares worth almost $5.6 million on Monday as part of a pre-planned sale on the day of the vaccine news release – which sent the company’s stock price soaring.

Feature image courtesy of Rocky Mountain Laboratories/NIH

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NICE backs chemo-free CLL combination from AbbVie and Roche

Previously treated patients with chronic lymphocytic leukaemia (CLL) in England will get a chemotherapy-free treatment option after NICE recommended NHS funding for a combination of AbbVie’s Venclyxto and Roche’s Gazyva.

The decision by NICE allows for the 12-month fixed duration treatment option based on data from the phase 3 CLL14 trial.

This showed the combination of Venclyxto (venetoclax) and Gazyva (obinutuzumab) had superior progression-free survival and sustained that benefit after stopping treatment compared with those receiving a commonly used chemoimmunotherapy regimen of Gazyva and chlorambucil chemo.

NICE recommended the combination in patients with del(17p)/TP53 mutation and those without del(17p)/TP53 mutation for whom fludarabine, cyclophosphamide and rituximab (FCR) or bendamustine and rituximab (BR) are unsuitable.

The cost-effectiveness body also recommended the combination for use within the Cancer Drugs Fund (CDF) for patients without del(17p)/TP53 mutation and for whom FCR or BR are suitable, subject to a managed access agreement.

The combination therapy will be available to NHS patients in England immediately.

CLL is the most common type of chronic blood cancer, with around 10 new patients diagnosed every day.

Unlike some cancers, CLL has a highly variable clinical course so patients are usually left to ‘watch and wait’, after which some patients will be offered appropriate treatment.

However, despite novel therapeutic advancements in CLL, the disease remains incurable and patients will often relapse following treatment.

Professor Peter Hillmen, consultant in clinical haematology at Leeds Teaching Hospitals and honorary professor of haematology at University of Leeds, said that the treatment can produce a “deep response.”

“Ultimately, this has the potential to improve patients’ quality of life and reduce the significant burden of therapy,” he added.

The European Commission approved the combination therapy for the treatment of for adult patients with previously untreated chronic lymphocytic leukaemia in March 2020.

Venetoclax is being developed by AbbVie and Roche. It is jointly marketed by AbbVie and Genentech, a member of the Roche Group, in the US and by AbbVie outside of the US.

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Lilly to ship COVID-19 drug straight away after FDA green light

Eli Lilly has said it will start shipping supplies of its COVID-19 drug bamlanivimab immediately, after claiming emergency-use authorisation (EUA) for the antibody.

The AbCellera-partnered drug, previously known as LY-CoV555 or LY3819253, can be used to treat mild-to-moderate COVID-19 in patients 12 years and older, who are at high risk for progressing to severe disease that might require hospitalisation.

President Trump has previously pledged to make antibody drugs available for free to anyone who needs them, and his administration has already signed a $375 million contract with Lilly to supply 300,000 doses of the drug within two weeks of the EUA.

The US has also taken an option on another 650,000 doses of the drug between now and the end of June 2021.

Lilly chief executive David Ricks has also said that patients should have no out-of-pocket costs for the drug, although healthcare facilities may charge a fee for the antibody’s intravenous administration.

The EUA as well as the US government contract came despite the results of the ACTIV-3 trial run by the National Institute of Allergy and Infectious Diseases (NIAID), which halted enrolment in the bamlanivimab arm because data to date suggested the drug was unlikely to be effective in hospitalised patients.

The FDA approved a 700mg single IV dose of the drug based on the phase 2 BLAZE-1 trial, which showed a reduced rate of hospitalisation in patients at high risk of COVID-19 progression who were treated with the antibody in the outpatient setting.

The NIAID is also running another study of Lilly’s antibody, ACTIV-2, which involves outpatients with mild-to-moderate COVID-19 symptoms.

Lilly says it will ship supplies of the drug to AmerisourceBergen, which will handle distribution once a week in accordance with the US government’s allocation plans. Where the drug is distributed will depend on confirmed COVID-19 cases across the US over the prior seven days.

Bamlanivimab – an antibody that neutralises the SARS-CoV-2 coronavirus – joins Gilead’s antiviral Veklury (remdesivir) on the list of drugs with EUAs for COVID-19, but is the first to be cleared for use outside hospitals.

Veklury’s EUA and subsequent full approval by the FDA covers the treatment of patients with COVID-19 who already require hospitalisation. The FDA has also issued EUAs for convalescent plasma for hospitalised patients, as well as for certain drugs that don’t target the virus directly but are used to support patients whilst in acute care.

Lilly notes that bamlanivimab should be administered as soon as possible after a positive COVID-19 test and within 10 days of symptom onset.

The company says it hopes to be able to produce up to one million doses of bamlanivimab 700mg by the end of 2020, “for use around the world through early next year.”

The FDA is meanwhile reviewing an EUA for Regeneron’s COVID-19 antibody therapy REGN-COV2, focusing on patients with mild to moderate disease who are at risk of progressing, and a decision on that could be made shortly.

REGN-COV2 also seems at risk of falling short in hospitalised patients, after a safety concern led to the pause of enrolment in a clinical trial in this setting earlier this month.

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NHS set to roll out COVID-19 shot in New Year, says health secretary

The UK’s NHS is ready to start rolling out a coronavirus vaccine, likely beginning in the new year, according to health secretary Matt Hancock.

In an interview with the BBC Hancock said that the vaccine could be available by Christmas, but he expected a mass roll out “in the first part of the new year”.

Vaccination clinics would be open seven days a week and he said he is giving an extra £150 million to run them.

But he urged patience, saying it is unclear how many people will have to be vaccinated before life can return to normal.

Hancock made the comments after the landmark announcement from Pfizer and its partner BioNTech that their COVID-19 vaccine protected about 90% of patients from the disease in a phase 3 trial.

The UK government has ordered 40 million doses of Pfizer’s vaccine and European and UK regulators have begun rolling reviews of the most advanced vaccine candidates.

This allows the European Medicines Agency and the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) to review data in real time, reducing the time taken from more than a year to a matter of weeks.

As reported by pharmaphorum, the UK could get the vaccines before the EU if the MHRA is faster with its review.

The BBC said the review could be complete by the end of this month.

GPs have been told to prepare to give patients two vaccine doses, to be delivered between 21 and 28 days apart.

Clinics could run between 8am and 8pm, according to the British Medical Association.

Only small numbers of the vaccine will be given in December with most shots taking place in 2021.

The government also hopes that mass testing will also help to turn the tide, by giving people accurate information about whether they have the virus or not, allowing them to go about their business if they are clear.

Shortly after Pfizer announced its trial success, it emerged that another late-stage contender from China’s Sinovac hit a safety issue.

A clinical trial in Brazil was put on hold after health authorities reported a “severe adverse” incident.

The Brazilian health regulator Anvisa said the incident took place on 29 October.

There are 47 COVID-19 vaccines in clinical development and 10 in phase 3, according to a regularly updated document from the World Health Organization.

Feature image courtesy of Rocky Mountain Laboratories/NIH

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Divided Congress paves way for drug price reforms on Biden’s watch

Unless president Donald Trump is successful with legal challenges, Democratic rival Joe Biden looks to have won the White House in last week’s election but faces the challenges of a divided Congress when it comes to implementing important health policies.

Making healthcare affordable is one of Biden’s goals as many Americans struggle to pay for healthcare, including those who have lost their jobs in the pandemic and with it their health insurance schemes.

High drug prices was a touchstone issue in the 2016 elections and Biden has also made this a priority in his campaigning.

Brian Bewley, partner in the life sciences and healthcare practice at corporate law firm Goodwin, said: “President-elect Biden has consistently prioritised affordable healthcare for all.  This includes reducing drug costs to consumers in the United States.

“In order to accomplish this, Biden has proposed allowing US Government agencies to negotiate directly with pharmaceutical manufacturers on drug pricing, enacting legislation to effectively limit or cap drug prices (brands and generics), and allowing consumers to purchase drugs from foreign countries.

“If any of these are successful, it could materially impact profit margins for the drug manufacturers.”

The Senate elections have not been decided and at the time of writing the House of Representatives is set to remain under control of the Democrats by the slimmest of margins.

This means that Biden will have to use all his charm and persuasion to bring legislators in line in a Congress that is reflective of the rifts in US society, although he may have support for drug price reform, according to Goodwin.

He said: “Right now, the Senate majority hangs in the balance with Democrats and Republicans holding at 48 seats each, with four seats outstanding.  That said, it appears that if Republicans have a majority, it will be by a slim margin.

“When it comes to President-elect Biden’s agenda on reducing drugs costs, he may have bi-partisan support – especially when you consider that the current administration under President Trump also tried to address drug pricing and transparency.”

According to Goodwin many states have been more aggressive than the Federal government on drug pricing and at least 15 have passed prescription drug price transparency laws, requiring manufacturers to report price increases exceeding a certain threshold.

These laws are meant to help states identify generics for their own prescription drug development programmes.

“I don’t see states being a major obstacle or impediment to President-elect Biden’s agenda on drug pricing as the states have, in many ways, outpaced their federal government counterpart,” said Goodwin.

Obamacare and COVID-19

Biden is an architect of the Affordable Care Act  and helped to implement the legislation as vice president of the Obama administration.

He will attempt to expand this legislation, nicknamed “Obamacare”, after Trump’s Republicans unsuccessfully tried to unpick it with their withdrawn American Health Care Act.

A likely addition to the legislation is a new “public option” to cover uninsured Americans and expansions of Medicare and Medicaid cover to older people and those on lower incomes respectively.

In the shorter term the COVID-19 pandemic will be a major focus as the country gears up to put together a mass vaccination programme.

Biden is an advocate of mask wearing, saying that doing so could save almost 70,000 lives.

But whether governors of Republican-leaning states will stand by his proposal to make mask-wearing mandatory outside their household is another matter.

The Trump administration became increasingly resistant to measures such as mask-wearing and social distancing played a part in the election, with Trump advising his supporters to attend polling stations in person and Biden urging his voters to use postal ballots instead.

Biden has set out proposals to improve testing and tracing, with the federal government taking responsibility for personal protective equipment (PPE) for healthcare workers.

Other measures include allowing the Centers for Disease Control to take the lead on how to control the disease with social distancing measures.

His seven-point pandemic plan also outlines proposals to protect higher-risk groups such as older people and these from certain ethnic minority groups.

He also plans to rebuild links with the World Health Organization, which Trump famously defunded after blaming it for failing to effectively control the COVID-19 pandemic.

As the world digested the news that Pfizer/BioNTech’s vaccine could be more than 90% effective Biden said he will make distributing a vaccine a priority.

With the rising cases every day, it’s the part of Biden’s plan that’s less likely to face political pushback, although there is distrust among the public about vaccines.

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After NICE okay, Scots denied access to Vifor’s Veltassa

The Scottish Medicines Consortium (SMC) has ruled that there’s not enough evidence to support NHS funding of Vifor Pharma’s Veltassa for excess potassium in the blood (hyperkalaemia), even though patients in England can access the drug.

It’s the second time that the SMC has rejected Veltassa (patiromer), having previously turned it down for hyperkalaemia in 2018.

Most common in patients with poor kidney function, heart failure or liver disease treated with renin angiotensin aldosterone system (RAAS) inhibitors, hyperkalaemia can be fatal, and patients have relatively few options for treatment.

The traditional standard of care has been to simply reduce the dosage of RAAS inhibitors, although there is evidence this can lead to cardiovascular death and worsening renal function. Clinical trials have shown show that Veltassa may allow patients to stay on RAAS inhibitors for longer or at a higher dose.

The SMC’s verdict creates a divergence in access to Veltassa in the UK as NICE cleared the drug for use by NHS England at the end of 2019, after also rejecting it in 2018. The change of heart for the cost-effectiveness agency came after new evidence and a price cut, according to NICE.

“We were unable to accept patiromer for hyperkalaemia as the company’s evidence about the medicine’s benefits was not strong enough,” said SMC vice chairman Scott Muir.

Some people in Scotland with hyperkalaemia do have a treatment option available, however, in AstraZeneca’s rival therapy Lokelma (sodium zirconium cyclosilicate). Both Veltassa and Lokelma work by binding phosphate in the gut and preventing it from being absorbed.

In September, the SMC gave a green light for restricted use by NHS Scotland of Lokelma, albeit only for patients with chronic kidney disease stage 3b to 5 and/or heart failure who would otherwise need to lower or stop RAAS drugs.

NICE backed AZ’s drug for that use last year, as well as for emergency treatment of acute life-threatening hyperkalaemia alongside standard care.

The SMC also backed several other medicines that have already been recommended for NHS use south of the border or are still under appraisal, including:

  • Akcea Therapeutics’ Waylivra (volanesorsen) for the treatment of familial chylomicronaemia syndrome (FCS);
  • Toche’s Tecentriq (atezolizumab) for metastatic triple negative breast cancer (TNBC) and extensive stage small cell lung cancer (ES-SCLC) in combination with chemotherapy;
  • PharmaMar/Johnson & Johnson’s Yondelis (trabectedin) to treat advanced soft-tissue sarcoma; and
  • UCB/Amgen’s Evenity (romosozumab) for the treatment of severe osteoporosis in postmenopausal women.

The SMC also backed two medicines via an expedited pathways that is designed to minimise delay in patient access during the COVID-19 pandemic, namely:

  • Bayer’s Nubeqa (darolutamide) for non-metastatic castration-resistant prostate cancer (nmCRPC); and
  • Roche’s Kadcyla (trastuzumab emtansine) for the adjuvant treatment of HER2-positive early-stage breast cancer, after neoadjuvant taxane-based and HER2 targeted therapy.

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FDA panel unimpressed with data for Alzheimer’s drug aducanumab

The FDA may have been minded to approve Biogen and Eisai’s Alzheimer’s candidate aducanumab, but its clinical advisors have little doubt that the evidence for the drug is lacking.

The much-anticipated advisory committee meeting held on Friday to discuss the marketing application for aducanumab proved to be a fractious affair, with both the companies’ data – and some of the FDA’s interpretation of it – under fire by panellists.

After hours of debate, the verdict from the experts was pretty unequivocal – 10 panellists voted against the main study supporting the drug, with just one saying they were uncertain about the data. Not one was convinced that the clinical trial results proved that the drug was effective.

The resounding rejection of the clinical data submitted in support of the marketing application for aducanumab came after the FDA published briefing documents that indicated the agency’s clinical reviewer was in favour of approval, calling the results “persuasive” despite a fairly damning assessment by the agency’s statistical expert in an appendix.

Aducanumab is vying to become the first Alzheimer’s drug designed to tackle an underlying cause of the disease, and the first new treatment for the neurodegenerative disease in almost two decades.

The FDA has been working closely with Biogen on the application and could still decide to approve the drug despite its experts’ reservations. That said, the balance of the votes makes that outcome unlikely – despite impassioned testimony during the virtual meeting by patient organizations.

The agency is due to make a decision by 7 March, and a review is also underway at the European Medicines Agency (EMA). Analysts have predicted it could become a multibillion-dollar blockbuster if approved, although at the moment that looks unlikely without another clinical trial.

An approval could also be seen as vindication for the hypothesis that tackling the amyloid plaques that are seen in the brains of people with the disease helps to slow the onset of symptoms. Many people had given up on the hypothesis after dozens of failed studies involving anti-amyloid drugs.

Biogen ran two identically-designed phase 3 studies of aducanumab – EMERGE (Study 302) and ENGAGE (Study 301) – to try to demonstrate that the anti-amyloid antibody could slow down the loss of cognitive function in people with mild cognitive impairment due to Alzheimer’s.

Last year, it called a halt to the studies after a futility analysis found it unlikely that aducanumab would show an effect on cognitive decline, but a few months later said that EMERGE was positive after all, and would form the basis of a marketing application with a phase 1b extension study – called PRIME – used as supportive evidence.

After a positive discussion of the results from Billy Dunn, acting director of the FDA’s office of neuroscience, the panel voted on three aspects of the data set.

In the first, they came down 8 to 1, with 2 uncertain, that the EMERGE trial could not be viewed on its own as providing strong evidence supporting aducanumab’s efficacy without taking into account the negative ENGAGE data.

They then voted 7 against and 4 uncertain on a question asking whether PRIME provide supportive evidence of the effectiveness of aducanumab in Alzheimer’s, before rejecting the premise that EMERGE could serve as primary evidence supporting the efficacy of the antibody.

Overall, the conclusion was that a negative interpretation of the data is just as likely as the positive one put forward by the trial sponsors, with one suggesting Biogen had shot first, and painted a bullseye later.

Biogen issued a short statement after the meeting in which CEO Michel Vounatsos said: “We appreciated the opportunity to share our data with the advisory committee, and we will continue to work with the FDA as it completes its review of our application.”

Trading in the biotech’s stock was halted ahead of the advisory committee meeting, but looks likely to be under considerable pressure when it resumes as it has been fluctuating wildly in reflection of the fortunes of aducanumab.

Biogen has a lot riding on aducanumab, as its pipeline has suffered recent setbacks including the failure of multiple sclerosis candidate opicinumab and a gene therapy for spinal muscular atrophy (SMA) at a time when big selling SMA drug Spinraza (nusinersen) is facing increased competition.

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After two decades, NICE begins consultation on drug assessment methods

The UK’s drug cost-effectiveness body NICE has launched a public consultation, presenting the case for change about how it assesses medicines, medical devices and diagnostics.

NICE has been assessing medicines for 21 years using the Quality Adjusted Life Year (QALY) – the cost to ‘buy’ a patient a year of quality life – as its main methodology.

Big pharma was never going to be happy about the existence of a body like NICE, which is designed to drive down prices paid by the taxpayer-funded NHS, by far and away the largest payer in the UK.

While industry has begrudgingly found ways to work with NICE to get drugs to the UK market, there have been numerous occasions where manufacturers have felt short-changed by the process and in some cases seen drugs failing to get funding on technicalities.

It’s still true that most drugs are eventually funded after a NICE assessment.

But the consensus is that despite tweaks to the system over the years, reform is needed to keep apace with developments in fields such as cancer.

NICE uses the Cancer Drugs Fund to provide interim reimbursement for cancer drugs that require more survival data and allows more flexibility for drugs used at the end of life.

And the cost-effectiveness threshold of £30,000 per QALY has not moved since NICE began, meaning that manufacturers’ wiggle-room on pricing has been constantly squeezed by inflation.

NICE’s consultation will ask whether additional factors should be included in decision-making, such as the severity of a condition and how health technologies can reduce health inequalities.

It is also asking whether there should be more flexibility in rare diseases, where generating evidence is difficult.

NICE wants feedback on how it assesses highly innovative technology, or those with potentially large benefits where risks could be managed.

The consultation will cover the role of evidence gathered outside clinical trials, such as real-world evidence and how NICE could refine its approach to measuring health-related quality of life in different circumstances.

NICE’s consultation follows an internal review of its number-crunching following commitments made in the voluntary pricing scheme that the government agreed with industry last year.

Steve Bates, chief executive of the Bioindustry Association said: “The proposed changes to NICE’s methods published today send an important signal to the innovative biotech sector that the UK is serious about ensuring access to new medicines.

“We are very encouraged by the focus on removing significant barriers to access, which puts the UK on a new footing, setting the benchmark for health technology appraisals – particularly around modifiers, uncertainty and discounting. It will help ensure both that industry can continue to deliver innovative medicines and that patients can access them.”

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Enabling innovation by connecting an ecosystem of partners

COVID-19 has been a shock to the system for every industry, not least pharma, but the sector is already looking at new ways to build resilience for the future.

Kevin Nikitczuk, INTIENT Network lead at Accenture, notes that collaboration and innovation are two of the key aspects that allow pharma to be ready for (hopefully unlikely) future situations akin to the pandemic.

“With COVID-19, the industry has realised that they need to accelerate and expedite everything they do – from identifying new targets to executing clinical studies to getting drugs onto the market.”

The sharing of knowledge has already been critical in the industry’s collaborative efforts to expedite a COVID-19 vaccine, and Nikitczuk believes that this open approach should extend beyond research into the software and data tools pharma uses every day.

A current problem, he notes, is that each of the many steps on this path requires different software tools – and most companies are using myriad different platforms within their organisation.

Part of this is an issue with unproductive competition – which can sometimes be a road blocker for innovation, particularly when proprietary technology is custom-built by niche players or developed in-house.

But it’s also true that over recent years – and especially during the course of the pandemic – the pace of technological growth in pharma has exploded, meaning there are more possible solutions available than ever, including more patient-facing technology such as telemedicine.

“We have some partners providing very similar tools to each other, and that’s okay, because we want to provide clients with options… I think that helps foster collaboration and encourages a little bit of healthy competition – which is always good for science”

This fragmented landscape creates issues for pharma.

“If, for example, regulations change or new standards for processing data come out, companies are going to face difficulties if they don’t have the proper infrastructure to quickly pivot out their software with new tools,” Nikitczuk says.

“Because of that, they may miss out on getting their products to patients in time.”

Nikitczuk believes that open, cross-company collaboration will be key to building flexibility and, ultimately, resilience against these difficulties.

Accenture, for example, decided to take its previously siloed platform products in areas as diverse as research, clinical studies and patient support and bring them under one umbrella.

The resulting INTIENT Platform brings together multiple third-party tools to allow continuity and flow of data across software and companies, whilst also facilitating insights delivered by artificial intelligence.

Rahul Kabra, INTIENT’s Europe lead, says he hopes the platform will streamline and accelerate collaboration across an entire product life cycle.

“We have partners providing patient facing capabilities in the form of medical devices or tools to enhance adherence. We also have partners providing the backend technology to secure personal data or manage workflows.

“Pharma and external partners can now use all these tools under one, end-to-end platform.”

In fact, Nikitczuk notes that clients themselves had a large role to play in pushing for a joined-up approach – showing that the spirit of collaboration in the industry is putting to rest any concerns that competition will continue to be a barrier.

“Our clients started pointing out that even though they were subscribed to several of our platforms, these tools weren’t talking to each other, and everything was still siloed.

“We took their advice and worked with them to bring these platforms together onto one end-to-end solution. Then we started working on bringing third-party vendors in. It’s been really great to see the collaborations blossom.”

To further this, Accenture is encouraging clients to develop their own software tools or bring their existing niche partners into the ecosystem and strengthen its capabilities.

It is also further encouraging open collaboration by keeping the platform solution-agnostic.

“We have some partners providing very similar tools to each other, and that’s okay, because some clients have a preference for certain vendors, and we want to be able to showcase that and provide clients with options.

“I think that helps foster collaboration and encourages a little bit of healthy competition – which is always good for science.”

Another reason for this approach is the fact that, traditionally, trying to get a software solution into a pharma company has been quite an endeavour.

“First you have to navigate procurement, which can be inhibitive for smaller start-ups. Even well-established firms struggle to get new products installed in large companies or even single departments which can be a time- and resource-intensive activity. We want to make this process incredibly fast.”

Nikitczuk adds that the more this partnership ecosystem and infrastructure is built up, the easier it will be to get future solutions onto the platform and into pharma companies.

Kabra adds that, as with pharma companies sharing knowledge to develop COVID-19 vaccines, he hopes that open collaborations like this in software will allow life science companies to take advantage of the collective intelligence of independent vendors who have poured all their time, energy, and passion into developing solutions – which, in turn, will enable the industry to  push boundaries and accelerate innovation.

“By being more open, the industry can allow companies the flexibility to test and implement new, potentially game-changing technologies,” Kabra says.

“We might even see the days of laborious, expensive, and inefficient procurement and implementation processes become a thing of the past.”

This is part of the draw of true open collaboration – when different companies are aligned to the same goals, processes that once took months to do can be done in days, or even less.

“As the biopharma landscape grows and evolves, we must continue to uncover new insights and innovative uses for data,” says Kabra. “By doing so, we develop new opportunities to raise the standard and personalisation of patient care and accelerate treatments to market.”

Luckily, it seems that the industry is more than ready to be truly collaborative and drive this collective mission forward.

To learn more about how Accenture is bringing companies together, click here.

About the interviewees

Kevin NikitczukKevin Nikitczuk is a senior principal within Accenture’s Life Sciences, leading the network partnerships for the INTIENT platform. Kevin has an in-depth working knowledge of life science R&D after years of laboratory and corporate experience within the pharmaceutical, biotechnology, and medical devices fields. Kevin earned a PhD in Immuno-Oncology from Rutgers University and has published peer-reviewed articles on his work and holds several patents.

Rahul KabraRahul has over 25 years’ experience in technology strategy, innovation, global partnerships and solution development. He has previously held positions as a Strategy Lead for Accenture’s Products Group, and as the Ecosystem and Ventures Lead for Accenture Technology. Rahul holds a degree in Computing from City University London, and an MBA from Henley Business School.

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Pharma may avoid worst-case drug pricing scenario as US elections deadlocked

Pharma may have avoided a worst case scenario amid the political upheavals in the US elections with the threat of tough drug price legislation lowered, with hawkish Democrats unlikely to win overall control of Congress.

With the outcome of the presidential race unclear at the time of writing, Democrats likely to back tough drug pricing legislation may not have won the majority needed to control the Senate, although they look to have maintained control of the lower House of Representatives.

The Democrats need to “flip” two seats in Georgia to win a slim majority in the upper house and analysts said the party doesn’t have the influence it needs to effect radical change on drug pricing in the US.

According to a team of Jefferies analysts led by Peter Welford a Democrat clean sweep would have been “optically concerning” for pharma because of the party’s tougher stance on medicine prices – a vexed issue in the US where many patients pay all or part of prescription costs.

The pharma sector’s “sharp uptick” yesterday was also down to the FDA’s publication of briefing documents from the FDA that suggest Biogen’s Alzheimer’s drug aducanumab could be approvable ahead of an influential meeting of the regulator’s advisers tomorrow.

If Joe Biden is confirmed as president, Jefferies said it is less clear on his top priorities for pharma, although an expansion of the Affordable Care Act – also known as ‘Obamacare’ – could be likely.

A Biden presidency is likely to favour tying drug prices to the lowest price from a basket of developed-world countries for Medicare drugs administered by doctors (part B).

It would also aggressively push this policy for self-administered (part D) Medicare drugs, according to Jefferies.

If Trump remains in the White House he would also pursue this “most favoured nation” policy on drug pricing for part B drugs, and potentially for part D drugs.

Roche is most exposed to this pricing reform, potentially hitting sales of its recently launched drugs Ocrevus for multiple sclerosis, Hemlibra for haemophilia, and Tecentriq for various types of cancer.

These drugs were supposed to replace sales lost as Roche’s older cancer drugs Rituxan, Herceptin and Avastin were hit by biosimilar competition, although the effect may not be as marked in the US where price differences between old and new drugs are less marked.

Biden’s proposals for hikes to US corporation taxes could be more punitive for Roche than for other pharma companies, translating into a 4-5% cut in earnings per share according to Jefferies.

 

 

 

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Trials and tribulations in Biogen’s Alzheimer’s drug reviews

Regulatory reviews of Biogen’s Alzheimer’s drug aducanumab are now ongoing on both sides of the Atlantic, but debate is still ongoing about whether the data behind the drug is strong enough to support approval.

The EMA has just kicked off its review of the anti-amyloid therapy, following in the footsteps of the FDA in the US which has been looking at the drug since August, but a new analysis of the mixed phase 3 data for aducanumab argues that an additional trial should be carried out.

The paper in the journal Alzheimer’s & Dementia, led by Mayo Clinic neurologist David Knopman, says that efficacy of aducanumab “as a treatment for the cognitive dysfunction in Alzheimer’s disease cannot be proven by clinical trials with divergent outcomes.”

Meanwhile, the paper also notes that Knopman has been excluded from an FDA advisory committee meeting due to discuss the data on Friday, ahead of a decision on the marketing application due in March.

The expert – who was an investigator in the phase 3 trials of Biogen’s drug – told Reuters he was recused from the panel because of his involvement in conducting clinical trials of aducanumab.

Aducanumab – which Biogen is developing with Japanese drugmaker Eisai – was all but abandoned in 2019 after the partners decided that two phase 3 trials of the drug were unlikely to show an effect on cognitive decline in Alzheimer’s.

Shares in Biogen were hit hard, as investors lost hope that aducanumab might be rescue the almost defunct amyloid hypothesis of Alzheimer’s disease, which holds that blocking the formation of amyloid plaques in the brain could delay the onset of dementia.

Just a few months later however they said a fresh look at the results of the EMERGE and ENGAGE studies had revealed that the initial futility analysis was “incorrect.” In fact, the drug reduced clinical decline in patients with early, a chance was put down to more exposure to a higher dose in additional patient follow-up.

Some patients showed statistically significant improvements on symptoms like memory, orientation, and language, as well as being able to carry out day-to-day tasks more easily.

There’s a lot riding on the FDA and EMA reviews. If approved, aducanumab will become the first therapy to reduce the clinical decline of Alzheimer’s and to change the course of the disease, says Biogen. It would also be the first amyloid-targeting drug to reach the market, after dozens of others have failed in clinical development.

Meanwhile, aducanumab is the big hope in Biogen’s late-stage pipeline, which otherwise is looking fairly thin, at a time when the biotech is facing the loss of patent protection for its blockbuster multiple sclerosis therapy Tecfidera (dimethyl fumarate).

Knopman and fellow authors argue in the Alzheimer’s & Dementia paper that Biogen’s interpretation of data in the two trials might not be correct.

They write that they have found alternative explanations for the apparent drug benefits unrelated to the treatment, and say that while there is evidence that aducanumab was working on amyloid and other biomarkers like tau protein as expected, “no evidence was presented to correlate biomarker changes to cognitive benefits.”

They also say there were differences in the placebo responses between the two studies, which could have contributed to the divergent results.

“Our analysis supports the conduct of a third, definitive phase 3 trial with high‐dose aducanumab [that is] optimally designed and adequately powered to prove efficacy,” they conclude.

The FDA has not commented on the reasons for Knopman’s exclusion from the advisory committee meeting publicly, but in these cases there is usually a conflict of interest.

Along with his involvement in EMERGE and ENGAGE, Knopman also serves on a data safety monitoring board for a tau drug for Alzheimer’s developed by Biogen, and is an investigator in a trial sponsored by Eli Lilly and the University of Southern California.

He also performs unpaid consultancy work for Samus Therapeutics, Third Rock, Roche, and Alzeca Biosciences, according to the paper’s conflict of interest statement.

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Price cut leads NICE to back Novo Nordisk’s obesity drug Saxenda

Novo Nordisk’s Saxenda has been recommended by NICE as a treatment for obesity, ending a 10-year drought in new drug therapies for weight management.

The cost-effectiveness agency for England and Wales has recommended Saxenda (liraglutide) as a treatment option for people with a body mass index (BMI) of 35 or more, and who are also pre-diabetic with a high risk of developing cardiovascular disease because of risk factors such as high blood pressure or high cholesterol levels.

NICE tuned down the GLP-1 agonist earlier this year, but changed its stance after Novo Nordisk offered a confidential discount to the NHS.

Saxenda – which comes as prefilled self-injection pen – will be used as part of a programme based on a reduced-calorie diet and increased physical activity, according to NICE, and treatment should be discontinued if patients don’t lose at least 5% of their body eight within 12 months.

“Our independent committee was presented with clinical evidence which showed that people lose more weight with liraglutide plus lifestyle measures than with lifestyle measures alone,” said Meindert Boysen, NICE’s deputy chief executive.

“Liraglutide may also delay the development of type 2 diabetes and cardiovascular disease and this is the main benefit of treatment,” he added. It will be prescribed in secondary care, by a specialist multidisciplinary tier 3 weight management service.

Denmark-based Novo Nordisk said there are 13 million obese people in England with obesity, placing them at risk not only of diabetes and heart disease but also severe COVID-19 symptoms if infected with SARS-CoV-2.

The NICE recommendation coincided with Novo Nordisk’s third quarter results statement, which showed modest 3% growth for Saxenda in the first nine months of the year to DKK 4.2 billion ($661 million), held back by the impact of the pandemic on patients accessing healthcare.

That also put a brake on Novo Nordisk’s other products, which are mainly use for chronic diseases like diabetes, although it said a “gradual recovery” occurred in the third quarter. All told, sales grew 7% in the nine months to just under DKK 95 billion ($14.9 billion).

Saxenda continues to develop a dominant position in obesity pharmacotherapy however, and Novo Nordisk said the drug currently has a market share of 63% worldwide.

The company’s GLP-1 agonists for diabetes grew strongly, thanks to its once-weekly injectable Ozempic (semaglutide) which grew  119% to DKK 15 billion ($2.35 billion), overtaking Novo Nordisk’s older Victoza (liraglutide) product which requires dosing by injection every day.

Ozempic is squaring off in the market against Eli Lilly’s Trulicity (dulaglutide), which grew 22% to $3.57 billion in the same period.

Novo Nordisk also recorded DKK 1 billion ($156 million) in sales for its new oral formulation of semaglutide – Rybelsus – which started to roll out this year.

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NICE talking to you: Trends in early HTA engagement

With exclusive data from Freedom of Information (FOI) requests sent to the National Institute for Health and are Excellence (NICE), Leela Barham takes a look at the trend in early engagement with the UK’s HTA body.

In 2009, NICE was one of the first health technology assessment (HTA) agencies to offer the opportunity for early scientific advice, at a cost. The fees range from £20,000 to £75,000 per project. They are based on cost-recovery.

The idea behind this service is help companies understand the agency’s point of view on evidence; the gaps and how to fill them before the appraisal. Ultimately the idea is to help companies achieve patient access.

The NICE scientific advice service includes a standard approach (taking around 18 weeks) and an express scientific advice service (taking around 12 weeks). The standard approach offers the most in-depth option. Companies ask questions through the service, often on:

  • Clinical trials, design and analysis
  • Trial populations
  • Outcomes
  • Comparators
  • Quality of life data
  • Economic analyses (modelling, extrapolation, resource use and costs)

The service is popular; over the eleven years it’s been used on average almost 18 times each year although take-up has varied over time (see figure 1).

“Getting advice with NICE as part of the dialogue with others has proven to be more popular than talking to the agency alone. It’s not clear how far advice from NICE alone is a substitute for getting advice as part of a bigger conversation”

Figure 1: NICE early scientific advice projects, 2009/10 to 2019/20

Source: Data from NICE FOI responses. Note the light service has been incorporated into the standard service. Light was previously aimed at small and medium sized enterprises.

Since 2009 the agency has added further charged-for services; in 2015 NICE added the Office for Market Access (OMA). OMA can offer a safe harbour for discussions with NICE, NHS commissioners and other stakeholders. This has proven popular too and has seen a steady increase in safe harbour meetings held over time (figure 2).

Figure 2: NICE OMA safe harbour meetings, 2016/17 to 2019/20

Source: Data from NICE FOI responses.

By 2017, NICE added the Preliminary Independent Model Advice (PRIMA) service. PRIMA is a way to get the agency to check health economic models, taking either 12 weeks for the standard service, or eight weeks for an express service. The service was used twice in 2017/18, four times in 2018/19 and three times in 2019/20 according to FOI responses from NICE.

There are good reasons to want to engage PRIMA. Researchers analysed single technology appraisals completed in 2017 by NICE, looking specifically at technical errors and validation processes reported on the economic models submitted by companies. Only two STAs (5%) had no reported errors. Four STAs had more than ten errors (10%). That prompted Jeanette Kusel, director at NICE Scientific Advice, to highlight on LinkedIn the importance of the PRIMA service for checking models prior to submission.

Engaging with NICE, regulators and other HTA agencies

There are also other services that NICE can be part of in providing early advice. The agency has been a popular choice as part of the EUnetHTA early dialogue offer and has also been one of the HTA agencies taking part in EMA-multi-HTA early dialogues. With Brexit though, NICE has set up a concurrent scientific advice service for when companies want advice from EMA and the UK body at the same time. The latest option is with NICE and the Canadian Agency for Drugs and Technology in Health (CADTH) together. The NICE-CADTH service was launched in 2019. It’s not had long enough to really get a track record, even more so when COVID-19 saw CADTH temporarily suspend the service.

Getting advice with NICE as part of the dialogue with others has proven to be more popular than talking to the agency alone (see figure 3). It’s not clear how far advice from NICE alone is a substitute for getting  advice as part of a bigger conversation with others. It’s likely though that hearing from NICE on their own will give a depth of advice that might not be possible in the limits of a meeting held with several other voices in the conversation.

Figure 3: NICE early scientific advice projects alone and with others, 2009/10 to 2019/20

Source: Data from NICE FOI responses. Note: EMA-HTA includes NICE concurrent services delivered in parallel to EMA-multi-HTA dialogue. 

What is the impact?

It is clear that the services to secure NICE advice are popular. The agency has a few testimonials on their website to support that. For example, for their scientific advice service, it quotes from a project feedback questionnaire:

“I truly value this Scientific Advice service… It creates fantastic opportunities for global drug development teams to better understand reimbursement hurdles and evidence requirements for timely market access. Great job!”

For PRIMA, the agency quotes Peter Wheatley-Price, market access and pricing director at Takeda UK, who said: “The Takeda team highly regarded the quality of the PRIMA reports and model review documentation. We appreciated the PRIMA team’s engaging and flexible approach at this pivotal stage in development and look forward to using the service as part of our model development efforts going forward.”

Yet it’s hard to know what difference they are making in terms of evidence strategies –what evidence will now be generated, and importantly for efficiency, what evidence won’t be generated because it won’t be valuable to the agency and payers in the UK – and ultimately, NICE recommendations. The services aren’t staffed by those who make the decisions later and it isn’t clear if Appraisal Committee members know if a company has sought advice, what that advice was, and whether it was acted upon by the company. There is a question over pull, through.

NICE has, so far, kept the details of which companies and which products have sought advice close to their chest. The various services offered are confidential and aren’t legally binding on both sides. Yet that doesn’t seem to explain why they can’t routinely release statistics about take-up of their services – it would be a real indicator of value if companies go back repeatedly for different products across their portfolios – nor why they can’t release details in the final guidance on whether advice was sought.

EMA does put into the public domain if a company has sought scientific advice and when. EMA keeps the details of the discussion out of the public domain. There is clear evidence that EMA scientific advice improves the chances of marketing authorisation.

Whilst companies who have sought advice from NICE will know the difference it has made or not, those companies who have yet to engage with the agency could be more likely to, if they know it can make a difference.

About the author

leela barhamLeela Barham is researcher and writer who has worked with all stakeholders across the health care system, both in the UK and internationally, on the economics of the pharmaceutical industry. Leela worked as an advisor to the Department of Health and Social Care on the 2019 Voluntary Scheme for Branded Medicines Pricing and Access (VPAS).

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US buys Lilly COVID antibody, as effectiveness questions remain

The US government said it will buy 300,000 doses of Eli Lilly’s COVID-19 therapy bamlanivimab for $375 million if the drug gets Emergency Use Authorisation (EUA) – despite the fact its effectiveness has been called into question.

The initial agreement is for delivery over the two months following an EUA, and provides the option for the government to purchase up to an additional 650,000 vials through 30 June 2021.

Lilly filed for emergency use authorisation (EUA) of bamlanivimab for the treatment of recently diagnosed mild to moderate COVID-19 illness in high-risk patients in early October.

The US has said that patients will have no out-of-pocket costs for the medicine – echoing a promise by Lilly CEO Dave Ricks – although healthcare facilities may charge a fee for the product’s administration. 

The federal government, in partnership with state health departments, is developing a government allocation program for bamlanivimab.

Ricks has said that the company “must work with global health systems to ensure equitable access to our medicine at a fair price”.

“Our goal is to ensure that Lilly antibody treatments are available to patients who need them, no matter where they live.

“As long as supply of neutralising antibodies is constrained, we believe the only way to ensure equitable access is for Lilly to contract directly with governments and pan-national philanthropic organisations. These institutions are best positioned to direct our antibody treatments to the patients who need them most.”

He added that treatment allocation will be based on unmet medical needs globally and that  equitable government pricing will be tiered based on a country’s ability to pay.

But the news might be dampened somewhat by this week’s announcement that no more patients will be treated with bamlanivimab in a trial run by the National Institute of Allergy and Infectious Diseases (NIAID), as results to date suggest it is unlikely to be effective.

The ACTIV-3 study was comparing bamlanivimab (also known as LY-CoV555 or LY3819253) and placebo when added to therapy with Gilead Sciences’ Veklury (remdesivir), which is already approved to treat COVID-19 requiring hospitalisation.

According to Lilly, the NIAID took its decision on the strength of trial data  which indicated that bamlanivimab – an antibody that neutralises the SARS-CoV-2 coronavirus – was unlikely to help hospitalised patients recover from advanced-stage COVID-19.

The drugmaker stressed however that other trials of its drug in COVID-19 are still continuing, and it pointed out that the earlier BLAZE-1 study of bamlanivimab showed a reduced rate of hospitalisation in patients treated with the antibody in the outpatient setting.

It also said it “remains confident…that bamlanivimab monotherapy may prevent progression of disease for those earlier in the course of COVID-19.

ACTIV-3 is a substudy of a larger, 10,000-patient trial that is putting a series of COVID-19 drugs through their paces, and Lilly’s drug is the only arm to include an antibody targeting SARS-CoV-2. In each case, 300 patients are enrolled initially before a decision is taken whether to expand the trial to 1,000 subjects.

In a statement, the NIAID said enrolment of patients into the bamlanivimab was paused on 13 October after 326 had been recruited, “out of an abundance of caution”, and terminated on 26 October.

There were no safety issues – the decision was “driven by lack of clinical benefit for LY-CoV555,” according to the agency – and the patients will continue to be followed for 90 days’ follow-up.

The NIAID is also running another study of Lilly’s antibody, ACTIV-2, which involves outpatients with mild-to-moderate COVID-19 symptoms, and that is continuing as planned.

BLAZE-1 is also continuing – looking at bamlanivimab alone and in combination with etesevimab (LY-CoV016) another Lilly antibody targeting SARS-CoV-2 – and the company is also running the BLAZE-2 trial of bamlanivimab as prophylaxis against COVID-19 in nursing home residents and staff.

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FDA sets April verdict for Pfizer’s “underestimated” atopic dermatitis drug

Pfizer could be just a few months away from getting FDA approval for its JAK1 inhibitor abrocitinib in atopic dermatitis, a drug that CEO Albert Bourla believes hasn’t been given the credit it is due by Wall Street analysts.

The US regulator has started a priority review of abrocitinib for mediate to severe atopic dermatitis in patients aged over 12, setting up a decision next April, while the EMA has also started a standard review that could lead to approval in the EU in the second half of 2021.

Bourla told analysts on Pfizer’s results call yesterday that abrocitinib is “the one potential near-term compound where we see the biggest difference compared with consensus.”

Pfizer sees abrocitinib and other JAK drugs coming through the pipeline for atopic dermatitis as expanding the number of patients getting treatment for the more severe end of the spectrum of symptoms – and it reckons that unlocks blockbuster sales potential.

“This is not a zero-sum game with the biologics in the treatment of moderate to severe atopic dermatitis,” said Bourla.

These patients currently rely on biologic drugs like Sanofi and Regeneron’s Dupixent (dupilumab), which dominates the category and saw sales rocket to more than $2 billion last year.

Sanofi sees plenty of additional upside, suggesting the drug could become a $10 billion brand at peak from expansion in atopic dermatitis as well as new indications like asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis.

Abrocitinib has previously been shown as effective in the JADE-MONO-1 and JADE-MONO-2 trials in subjects aged over 12, with a profile that looks like it could challenge its biologic rivals.

In particular, Pfizer says the drugs seem to have an impact on itch – often cited as the most bothersome symptom by atopic dermatitis patients.

Bourla and Angela Hwang – group president of Pfizer’s biopharmaceuticals division – think analysts are overlooking the sheer scale of atopic dermatitis as a condition with around 60 million sufferers aged over 12 worldwide.

They are also discounting abrocitinib’s profile, and the fact that almost two-thirds of patients treated with Dupixent don’t achieve clear or almost clear skin at 16 weeks, leaving room for improvement.

“Of those 60 million, only 7% of them today are being treated with a systemic agent,” said Hwang on the call. “So the systemic market opportunity has real potential to more than double with the introduction of better systemic treatment, because the patient need is just so high.”

There’s a precedent for that level impact for new biologic drugs such as interleukin inhibitors for psoriasis, which doubled the market over a 10-year period.

Claiming just 8% of the systemic atopic dermatitis treatment market would equate to $3 billion in abrocitinib sales, said Hwang.

Pfizer’s drug seems to have a lead in atopic dermatitis over other JAK inhibitors, although AbbVie has trials on the go for its fast-growing Rinvoq (upadacitinib) rival in this indication – including a head-to-head comparison with Dupixent due to read out next year.

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Russia’s COVID-19 vaccine filed with WHO, as MHRA reviews Moderna shot

Russia’s sovereign wealth fund has filed applications with the World Health Organization (WHO) that if approved could see the Sputnik V coronavirus vaccine backed for use in many countries around the world.

The applications are for two WHO mechanisms, aimed at providing a route to market for vaccines, drugs and other healthcare products that answer public health needs, particularly in low- and middle-income countries.

The Russian Direct Investment Fund (RDIF) has filed the state-owned Gamaleya Institute’s Sputnik V (Gam-COVID-Vac) for emergency use listing (EUL) – a process set up in response to Ebola that provides a route to approval for use of medicines for public health emergencies by WHO member states.

It is also going after WHO prequalification, which mainly covers essential medicines and supports use by the UN and other non-governmental organisations.

Both mechanisms cover review of safety and efficacy data, as well as ensuring the product meets manufacturing and quality assurance standards. Gilead Sciences COVID-19 therapy Veklury (remdesivir) was added to the prequalification list earlier this month.

Russia has reportedly been discussing prequalification of the Sputnik V with the WHO since the summer. In a statement, the RDIF said WHO registration “will make the Russian vaccine available globally in a shorter time frame than usual procedures and will support global efforts to prevent the coronavirus infection.”

Approval would also allow Sputnik V to be included in the list of medicines used by international procurement agencies and countries to guide bulk purchasing of medicines.

The applications come after Russia approved Sputnik V in August, the first coronavirus vaccine worldwide to get a green light, and after the country said it has accepted orders for 200 million doses of Sputnik V from Brazil, India and Mexico. It has suggested it will be able to make a billion doses of the shot per year from 2021.

There has however been some debate about the lack of data behind the shot, and concerns that Russia rushed development to claim a political victory in the race to get a COVID-19 vaccine approved.

Preliminary results published in The Lancet last month covered just 76 people, which found an antibody response within 21 days and T-cell response within 28 days, with no serious adverse events recorded out to 42 days of follow-up.

It is in two phase 3 trials, including the RESIST study which has a target enrolment of 40,000 subjects and is due to generate results in the spring.

The vaccine is based on two adenovirus vectors (Ad5 and Ad26) fused with the spike protein from the SARS-CoV-2 coronavirus. Immunisation requires two doses, with the Ad26-based shot given first and the Ad5 21 days later.

“We express our gratitude to WHO for its active cooperation and look forward to the successful completion of the prequalification process at all major stages,” commented Kirill Dmitriev, CEO of the RDIF.

The WHO’s regularly updated listing of COVID-19 vaccines in development puts Sputnik V sixth out of 44 candidates that have advanced into human testing.

UK starts review of Moderna’s mRNA-1273

Separately, the UK Medicines and Healthcare products Regulatory Agency (MHRA) has kicked off a rolling review of another late-stage coronavirus vaccine – Moderna’s mRNA-1273 – shortly after the US biotech completed enrollment in the phase 3 COVE trial.

The UK agency has started its review of the jab before the European Medicines Agency (EMA), but after a rolling review for mRNA-1273 was started in Canada.

The rolling submission allows regulators to start looking at available preclinical, manufacturing and clinical data in advance of the readout of COVE, potentially shortening the review time.

If COVE is positive and mRNA-1273 gets approved, Moderna has said it is on track to deliver up to 500 million doses per year, and possibly up to a billion doses per year beginning in 2021.

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AZ, J&J COVID-19 vaccine trials okay to restart in US

US trials of AstraZeneca’s experimental COVID-19 vaccine AZD1222 have been cleared to restart by the FDA, several weeks after testing was suspended following a serious adverse reaction in one patient who received the shot.

Separately, Johnson & Johnson has also announced it is resuming recruitment in a phase 3 trial of  its coronavirus candidate JNJ-78436735, which has also suspended after one study subject fell ill.

AZ confirmed the FDA’s move in a statement, saying that regulators in the US, UK, Brazil, South Africa and Japan have now said that trials of the Oxford University-partnered shot are safe to continue.

The FDA took a lot longer to reach its conclusion however, as recruitment into studies restarted just a few days after the halt elsewhere.

AZ chief executive Pascal Soriot said: “We should be reassured by the care taken by independent regulators to protect the public and ensure the vaccine is safe before it is approved for use.”

On 6 September, AZ said it had put trials of AZD1222 on temporary hold because of a potential safety issue involving one patient in the UK, who had become ill after taking the vaccine with what at the time was reported to be transverse myelitis – an inflammation of the spinal cord that can be associated with viral infections as well as neurological conditions like multiple sclerosis.

“It is not unusual that in large scale vaccine trials, some participants will become unwell, and every case has to be evaluated to ensure the careful assessment of safety,” said AZ, which hasn’t confirmed the nature of the adverse reaction.

A report in the Wall Street Journal suggests that the FDA has reviewed two cases of potential neurological side effects in patients receiving AZD1222. One was subsequently found to be in a patient with MS, but the US regulator couldn’t either identify or rule out a clear link to the vaccine in both cases.

A death has also occurred in a patient enrolled onto an AZD1222 study in Brazil, although that has not been linked to the vaccine and is believed to have occurred in a subject who did not receive the shot.

AZ is now expecting to have results from the trials before the end of the year – analysts at Jefferies think it could occur in mid-November – and rolling regulatory  reviews of AZD1222 are already underway in some markets including the EU.

J&J meanwhile said that the independent data safety monitoring committee overseeing the phase 3 ENSEMBLE trial of JNJ-78436735 had found no clear cause behind a “serious medical event” – reported to be a stoke – in one subject that caused the study to be placed on hold earlier this month.

“After a thorough evaluation of a serious medical event experienced by one study participant, no clear cause has been identified,” said the drugmaker in a statement indicating the findings had been shared with the FDA. “There are many possible factors that could have caused the event.”

The suspension of studies for AZD1222 and JNJ-78436735 has put two coronavirus vaccines from BioNTech/Pfizer and Moderna in the lead in the US, with top-line efficacy results due within the next 4-5 weeks, although safety data will take a little longer to come in.

The resumption of the two stalled studies means that AZ and J&J will now not be too far behind.

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Gilead’s remdesivir finally gets US approval

Gilead’s Veklury (remdesivir) has become the first COVID-19 drug approved in the US following a nod from the FDA.

As an antiviral drug, remdesivir works to stop replication of SARS-CoV-2, the virus that causes COVID-19.

Originally intended as a treatment for Ebola virus, remdesivir made headlines early on in the pandemic as the first drug to show significant improvements in recovery time in patients.

Until now, the drug – which will be marketed under the brand name Veklury – was only available to US patients under an Emergency Use Authorisation for the treatment of hospitalised patients with severe COVID.

In the meantime, it has been subject to a ‘rolling submission’ with the FDA that began in April. This has allowed Gilead to submit its application in small chunks as they were completed.

The approval is supported by data from two randomised, open-label, multi-centre phase 3 clinical studies of Veklury conducted by Gilead.

It also includes the phase 3 randomised, placebo-controlled study of Veklury conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

Data from the studies showed treatment with Veklury led to faster time to recovery compared with placebo and that a 5-day or 10-day treatment duration led to similar clinical improvement.

Across studies, Veklury was generally well tolerated in both the 5-day and 10-day treatment groups, with no new safety signals identified.

The drug has already been approved by several other regulators across the world, including in the European Union and Japan.

There are ongoing phase 3 trials testing its safety and efficacy in patients infected by the SARS-CoV-2 coronavirus that causes COVID-19, including combination trials with other drugs.

Last month a trial found that combining the drug with Eli Lilly’s rheumatoid arthritis drug Olumiant (baricitinib) reduces recovery time in COVID-19 patients compared to Veklury alone.

It hasn’t always been plain sailing in Veklury’s development journey, though, and some trials have shown more mixed results.

Earlier this month preliminary results from the World Health Organization’s large Solidarity trial suggested that the drug had failed to produce an effect on hospital stay and mortality.

Several other drugs are being tested as a treatment for COVID-19: one of the most promising is the off-patent steroid dexamethasone, which lowered mortality in a UK-based phase 3 trial and is considerably cheaper than Veklury.

Meanwhile, Roche announced this week that it will team up with Atea Pharmaceuticals to co-develop a rival to Veklury that can be taken orally outside of a hospital setting.

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Headache for Zosano as FDA turns down migraine patch

Zosano Pharma has been hit by an FDA rejection of its marketing application for migraine drug Qtrypta, asking for new bioequivalence data.

Qtrypta takes the form of a transdermal patch loaded with zolmitriptan, a well-established medicine for acute migraine that has been available for years in various formulations including tablets and nasal sprays.

Zosano’s product uses microneedles to help the drug get absorbed into the blood, but the Complete Response Letter (CRL) from the FDA says it is concerned about inconsistencies in how much zolmitriptan was being delivered with Qtrypta.

Specifically, the FDA pointed to differences in zolmitriptan exposures between subjects receiving different lots of Qtrypta in the company’s trials, including some unexpectedly high results in five individuals.

It also mentions “inadequate pharmacokinetic bridging between the lots that made interpretation of some safety data unclear.”

The CRL comes just a couple of weeks after Zosano received a discipline review letter (DRL) from the FDA, a preliminary sharing of the agency’s stance, after which the company had already said it did not expect approval by the action date of 20 October.

Shares in the Nasdaq-listed biopharma lost around 25% of their value after the announcement, as investors tried to gauge how long the programme might now be delayed, and the implications for its delivery platform, which is the first microneedle patch to be Included in a new drug application to the FDA.

Qtrypta is Zosano’s lead product candidate, but the company is also working on a follow-up in phase 2/3 for cluster headache.

The FDA wants a new bioequivalence study between three of the Qtrypta lots tested during development, as well as product quality validation data, originally due to be filed after approval, as part of the new drug application (NDA).

The agency also says that inspection of Zosano’s contact manufacturing facilities for the product – while currently on hold because of the pandemic – will also have to be completed before Qtrypta can be approved.

That suggests the delay could be some time, but Zosano is keeping tight-lipped until it has a chance to meet with the FDA to discuss a way forward for the programme.

“We are working diligently to address the deficiencies identified by the FDA and look forward to the possibility of resubmitting our NDA,” said the company’s CEO Steven Lo.

“There are thousands of people suffering from migraine attacks that are not adequately addressed with available drugs, and we continue to believe that Qtrypta, if approved, could offer a much-needed new therapy for these patients,” he added.

The company has previously reported data showing that Qtrypta can deliver fast relief from a migraine with fewer than 2% of patients experiencing side effects common with triptan drugs, like dizziness and pins and needles.

Zosano recently signed a five-year deal worth $250 million deal with Eversana to commercialise and distribute Qtrypta if gets past the FDA.

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Pfizer ‘ready to roll’ if BioNTech COVID-19 shot is approved

Pfizer now has hundreds of thousands of doses of BioNTech’s COVID-19 vaccine coming off the production line at a facility in Belgium, ready for delivery if it clears phase 3 testing.

The output of the plant in Puurs should allow the partners to have 100 million doses of BNT162b2 ready for delivery by the end of the year, according to a Mail on Sunday report, which claims 40 million of those doses are destined for the UK.

As two doses of the mRNA-based shot are required to stimulate an immune response against the coronavirus, that would be enough to vaccinate 20 million people.

The COVID-19 shot started a rolling review at the European Medicines Agency (EMA) earlier this month – which involves the agency evaluating data as they become available rather than in one block – and that means approval could come shortly after the 44,000-patient trial readout which is due by the end of this month.

Video footage of vaccine vials coming off the production line have generated excitement and puts Pfizer and BioNTech in pole position to get the first COVID-19 shot approved.

Pfizer is predicting a longer timeline in the US than Europe however, saying it won’t be able to file for emergency use authorisation in the US until the third week of November – assuming trials go as planned of course.

While top-line data on efficacy could be ready this month, at least half the recipients of the shot in the trial will have to be followed for safety for two months after the second dose, and that will set back the EUA filing.

That timescale dashes any chance of a feelgood coronavirus vaccine story for Donald Trump as he campaigns for a second term as US President. Pfizer and BioNTech were among a group of nine COVID-19 vaccine developers who pledged not to launch before thorough tests are completed.

The federal government agreed an initial order of 100 million doses of BNT162b2 in July, with an option on up to 500 million, and Pfizer and BioNTech reckon they have the capacity to make 1.3 billion doses next year.

The Pfizer update comes as the UK’s deputy chief medical officer Prof Jonathan Van-Tam suggested that Oxford University and AstraZeneca’s AZD1222 shot – based on a different technology – could be available in the UK “soon after Christmas”.

That timeframe would allow vaccination of elderly and vulnerable people as well as key workers to begin in the New Year, according to an article in the Sunday Times. The comments were made at a joint Commons and Lords national security strategy committee meeting.

Chief scientific officer Sir Patrick Vallance told the panel that a vaccine is unlikely to be widely available until next spring, and reiterated his view that the SARS-CoV-2 coronavirus will become endemic. However, he suggested it’s level of threat could be reduced to that of seasonal flu if effective vaccines are available.

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Novartis’ big bet on inclisiran nears fruition, as CHMP backs drug

Novartis’ near-$10 billion takeover of The Medicines Company last year was focused mainly on one asset – cholesterol-lowering drug inclisiran – and the Swiss pharma is now a step closer to getting a return on its investment.

Inclisiran – now give the trade name Leqvio – has been recommended for approval by the CHMP as a treatment for hypercholesterolaemia or mixed dyslipidaemia, two common forms of elevated cholesterol linked to increased risk of cardiovascular disease.

If approved, inclisiran would become the first and only gene-silencing drug to reduce low-density lipoprotein cholesterol (LDL-C) in these patients.

The drug inhibits PCSK9 – the same target as Amgen’s Repatha (evolocumab) and Sanofi/Regeneron’s Repatha (alirocumab) – but is dosed only twice a year rather than every month.

Novartis is hoping that with Leqvio it will make a mark where the antibody drugs have largely failed, with sales of Repatha and Praluent still failing to gather much momentum despite being on the market for more than five years, after pushback from payers that wasn’t overcome by substantial price cuts.

The big question for Novartis is whether Leqvio’s more convenient dosing will be enough for it to overtake its antibody-based rivals, given that they seem to be fairly equivalent when it comes to lowering LDL-C.

Novartis’ drug is also playing catch-up with its rivals on data from trials that show the reduction in LDL-C is matched by an improvement in cardiovascular outcomes.

Both Repatha and Praluent have that in hand, but Novartis will have to wait for the results of the ORION-4 study – due in 2024 – before it has a chance of matching the labels of Amgen and Sanofi/Regeneron’s drugs.

That said, Novartis is no stranger to building a slow-starting cardiovascular drug into a blockbuster franchise. It’s a trick it carried out with Entresto (sacubitril/valsartan) – a drug for heart failure – that after a sluggish roll-out is now bringing in sales at a rate of more than $2 billion a year.

That also means the Swiss drugmaker will also be able to push Leqvio through the sales channels that have made Entresto a blockbuster, but it will need to make swift progress if it is to get a reasonable return on the investment in MedCo.

Evercore ISI analyst Umer Raffat has previously said he thinks that will come if Leqvio hits $2 billion in peak annual sales.

Novartis already has some deals in place that could help it reach that target, including an access pact with NHS England aimed at accelerating access to Leqvio after EMA approval. Billed by Novartis as a “world-first”, the deal would see the drug made available to people with atherosclerotic cardiovascular disease.

Earlier this year analysts at Clarivate said they expect Leqvio to reach $1.16 billion in sales by 2024 as a treatment for elevated blood cholesterol among the 80% or so of patients who don’t respond to older statin drugs.

The CHMP sets up a likely EMA approval for Leqvio before the end of the year, and Novartis is also expecting to hear back from the FDA on the drug in the same timeframe.

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Lilly to buy private biotech Disarm Therapeutics for up to $1.36bn

Eli Lilly is to buy the private biotech Disarm Therapeutics, which is working on a new class of disease-modifying drugs for neurological diseases, in a deal worth up to $1.36 billion.

Massachusetts-based Disarm is focused on treatments for diseases caused by axonal degeneration, such as amyotrophic lateral sclerosis (ALS) and multiple sclerosis.

Disarm has discovered novel, potent SARM1 inhibitors and is advancing them into preclinical development for diseases including peripheral neuropathy as well as ALS and MS.

Axonal degeneration is a common yet unaddressed occurrence in a range of neurological diseases and is known to cause severe sensory, motor and cognitive symptoms.

Disarm’s scientific founders, Dr Jeffrey Milbrandt and Dr Aaron DiAntonio of Washington University School of Medicine in St Louis, discovered that the SARM1 protein is a central driver of axonal degeneration. Disarm’s SARM1 inhibitors are designed to directly prevent the loss of axons.

Lilly will pay $135m million up front for Disarm and shareholders may be eligible for up to $1.225 in further payments if certain goals are met if the big pharma develops and markets medicines resulting from the acquisition.

There will be no change to Lilly’s earnings per share guidance as a result of the deal.

While there are limited treatment options for ALS, the market for MS drugs is increasingly crowded with a range of different options including oral and injected medicines.

Roche has demonstrated the commercial potential for MS drugs after its Ocrevus (ocrelizumab) became a blockbuster after just a year on the market following its launch in 2017.

Migraine drug gets NHS funding

Lilly has also made some progress with its already-marketed neurology drug Emgality (galcanezumab), after NICE okayed NHS funding in final draft guidance applying to England and Wales.

NICE has already recommended Teva’s rival Ajovy (fremanezumab) this year, although it has rejected Novartis’ Aimovig (erenumab) despite an appeal from the manufacturer.

All the drugs come from the calcitonin gene-related peptide (CGRP) class of drugs, which patients inject to reduce the likelihood of attacks occurring.

NICE’s latest guidance recommends Emgality for preventing migraine in adults who have at least four migraine days each month and where at least three previous preventive treatments have failed.

This is the same point in the treatment pathway as Ajovy, but patients will have to experience at least 15 migraine days each month to be eligible for Teva’s drug.

 

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Regeneron’s antibody cocktail approved by FDA for Ebola

An antibody cocktail from Regeneron has been approved by the FDA as the first treatment for Ebola, offering hope that a similar approach could be used to combat COVID-19.

The FDA approved Inmazeb (atoltivimab, maftivimab and odesivimab-ebgn) for treatment of infection caused by Zaire ebolavirus in adults and children including newborns of mothers who test positive for the infection.

Approval was based on a large clinical trial where Inmazeb showed superiority compared with other investigational agents with respect to mortality, with treatment most effective when given early in the disease.

The therapy is based on a triple cocktail of monoclonal antibodies. Regeneron is using the same technology to develop the COVID-19 antibody combination famously given to president Donald Trump.

Regeneron has an agreement with the Biomedical Advanced Research and Development Authority (BARDA), a US government agency, to deliver an undisclosed number of doses of the drug over the course of six years after approval.

The New York- based company expects to receive around $10 million in 2021 under the deal signed earlier this year, and an average of $67 million per year for the next five years.

The drug has also been developed with funding from BARDA

In 2019, Regeneron’s randomised controlled PALM clinical trial was stopped prematurely when preliminary results showed that REGN-EB3 crossed the pre-specified superiority threshold for preventing death compared to the control arm.

Those in the control arm were treated with Mapp’s ZMapp, a rival cocktail of monoclonal antibodies.

Regeneron noted that its cocktail, codenamed REGN-EB3, outperformed ZMapp across several measures in the trial, including reduced mortality and fewer days until the Ebola virus was no longer detected in the bloodstream.

The trial involved nearly 700 patients and had three serious adverse events for REGN-EB3 compared with seven for ZMapp.

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Scynexis bids to end novel antifungal drought, filing ibrexafungerp in US

Scynexis has filed for FDA approval of its novel drug ibrexafungerp which – if approved – would be the first broad-spectrum antifungal to reach the US market for vaginal yeast infections in more than two decades.

The Jersey City, US-based biotech has submitted ibrexafungerp (SCY-078) on schedule as a treatment for the vulvovaginal candidiasis (VVC), a common yeast infection affecting one in three women during their lifetime.

The FDA has already granted Qualified Infectious Disease Product (QIDP) as well as fast-track status to the drug, setting up a possible approval in June 2021 and a launch next summer.

Currently there is only one approved drug for VVC – oral fluconazole – but a sizeable proportion of patients don’t respond well to the treatment. Resistance rates are rising and the drug is unable to be used in pregnant women as they are at a higher risk of VVC infections.

Ibrexafungerp is a member of the glucan synthase inhibitor class – which covers fluconazole as well as newer agents like caspofungin and micafungin that are administered intravenously – but has a new triterpenoid structure.

That makes it suitable for both IV and oral dosing, and also makes it fungicidal, in other words it kills fungi cells unlike some current drugs which only block fungal growth.

The filing in VVC is based on the results of two phase 3, placebo-controlled studies, VANISH-303 and VANISH-306, which had clinical cure rates of 50.5% and 63.3 and mycological cure rates of 49.5% and 58.5%, respectively.

That level of efficacy improves on results with oral fluconazole, according to analysts at Ladenburg Thalman, who think there is a potentially big market for ibrexafungerp, particularly among the approximately 650,000 women in the US who suffer recurrent VVC infections.

They think a lot of the drug’s use will come second-line behind fluconazole, but also point to market research by Scynexis that suggests 29% of physicians would use the drug as a first-line option, increasing to 59% for fourth-line treatment of recurrent VVC.

Assuming the drug is approved in the US next year and costs around $300 to $400, analysts believe sales could reach almost $240 million by 2025 then rise to $400 to $600 million.

Aside from targeting VVC, Scynexis is running two phase 3 trials of ibrexafungerp in refractory invasive fungal infections caused by Candida auris, called FURI and CARES, as well as the CANDLE study in recurrent VVC and SCYNERGIA, a mid-stage study of ibrexafungerp plus voriconazole in patients with invasive pulmonary aspergillosis.

“We believe that ibrexafungerp may be the modern antifungal therapy, that will have utility for a broad range of today’s fungal infection patients as fluconazole did almost 30 years ago,” said Scynexis’ chief executive Marco Taglietti.

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Regeneron joins Lilly in seeking emergency OK for COVID-19 antibody

Regeneron has followed Eli Lilly in asking the FDA for emergency approval of its COVID-19 antibody therapy, shortly after the drug was thrust into the spotlight by being used to treat President Trump.

The request for emergency use authorization (EUA) for REGN-COV2 comes amid a spike in interest about antibodies against the SARS-CoV-2 coronavirus, driven by Trump’s assertions that the drug was instrumental in his apparently swift recovery from the infection and is a “cure” for COVID-19.

That rise in demand is however already forcing a reality check about how many patients may be able to get REGN-COV2 treatment. In its statement on the EUA request, Regeneron says it has supplies available to treat 50,000 patients, adding that should rise to 300,000 “within the next few months.”

That’s far from what will be needed, points out former FDA Commissioner Scott Gottlieb in a tweet suggesting demand could be more than 7,500 patients per day.

The US has had more than 7.5 million cases of COVID-19 and 213,000 deaths to date, with around 50,000 new cases every day.

Regeneron has been working on ramping up manufacturing capacity for REGN-COV2, with the help of $450 million in funding from the US government, and recently enlisted the aid of Roche to expand capacity. The US has rights to the first 300,000 doses under that funding agreement.

Shares in Regeneron continued their inexorable rise on the news, with another surge after Trump’s comments, and the stock is now trading at twice their value from a year ago at close to $600.

The cocktail of two antibodies targets two components in the spike protein on SARS-CoV-2 with the aim of preventing attachment of the virus to host cells and interrupting infection.

The clinical data behind the EUA comes from a study in 275 patients, and looks promising. The latest readout from the trial showed the drug reduced both viral load and the time to alleviation of symptoms in non-hospitalised patients with COVID-19.

The greatest benefit was seen in patients who had not mounted their own immune response against the virus, according to trial investigators. Results in hospitalised COVID-19 patients are due later this year, and the antibody drug is also being tested for prophylaxis of SARS-CoV-2 infection.

There are still plenty of dissenting voices about REGN-COV2 however, suggesting that it’s far too early to make a judgment on how well it works.

One US physician pointed out that Trump was also treated with dexamethasone – a potent steroid shown clinically to improve survival in COVID-19 – that can make patients feel “20 years younger” – an effect reported by Trump.

The President was also treated with Gilead Sciences’ Veklury (remdesivir) – also shown to reduce the duration of symptoms in trials – as well as various other remedies including zinc and vitamin D supplements, the heartburn drug famotidine, melatonin and aspirin.

Regeneron’s request came hard on the heels of Lilly’s EUA filing for its antibody cocktail LY-CoV555 for use in higher-risk patients who have been recently diagnosed with mild-to-moderate COVID-19. The company has said it could be able to produce up to a million doses of the drug.

Meanwhile, other companies including AstraZeneca and GlaxoSmithKline/Vir are also working on antibody-based therapies for the disease. It’s clear however that if approved, these drugs will have to be used thoughtfully and sparingly to eke out limited supplies.

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EU ramps up supply of COVID-19 vaccine, drugs

The European Commission has taken its advance orders for potential COVID-19 vaccines to more than 1.1 billion, after signing a supply deal for up to 400 million doses of Johnson & Johnson’s experimental candidate.

The agreement is the third for coronavirus vaccine supply for the EU, coming after earlier deals with AstraZeneca and Sanofi/GlaxoSmithKline, and comes as wealthy nations are scrambling to secure access to the initial supplies of the shots furthest ahead in development.

If the vaccines are approved and the contracts are fulfilled, they would supply more than two shots apiece for each of the EU’s 446 million inhabitants.

In the US, Health and Human Services Secretary Alex Azar suggested this week that the country will have enough doses of vaccine available for every America citizen by March or April next year, with production underway for six shots backed by the US government across more than 23 manufacturing facilities.

The latest agreement involves an undisclosed down payment to J&J, whose vaccine started phase 3 trials in September. It covers an initial order for 200 million doses for EU member states, followed by an option on a second 200 million tranche.

The bloc ordered 400 million doses of AZ and the University of Oxford’s AZ1222 vaccine in August, and followed that up with a contract for 300 million doses of the Sanofi/GSK shot last month.

Just this week, it emerged that AZ has the right to declare an end to the pandemic in July 2021, having previously said it would supply AZD1222 at cost while the outbreak is still ongoing, according to a Financial Times report.

Remdesivir procurement

Meanwhile, the EC has also reached an agreement with Gilead Sciences to secure “rapid and equitable” access to its antiviral drug Veklury (remdesivir) – just as there are reports of shortages emerging around the world.

The joint procurement agreement (JPA) covers the 27 EU member states as well as the UK and European Economic Area (EEA) countries over a six-month period from later this month, and will do away with the need for country-by-country reimbursement negotiations, according to Gilead.

Veklury was granted conditional approval in the EU for the treatment of COVID-19 in adult and adolescent patients with pneumonia requiring supplemental oxygen in July, but by that time a large proportion of the drug’s supply had already been snapped up by the US government.

Gilead said in a statement that a “greatly expanded supply of Veklury is expected to meet European real-time demand and stockpiling needs in October.”

The company says it is on track to produce more than two million treatment courses of Veklury this year, and several million more treatment courses in 2021 if required. It’s ramped up production capacity internally and through a series of agreements with contract manufacturing partners.

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Pharma’s response to COVID: GSK

A few months into the pandemic, the world is now moving beyond managing the crisis, with more focus on addressing the collateral damages and shaping the future. As part of a new series looking at how pharma has responded to the pandemic, Neale Belson, SVP UK & Ireland and general manager for the UK at GSK, tells us that it is “absolutely critical” to do this with the pace and out-of-the box thinking of the past months.

Belson became GSK’s general manager in the UK in March, just before lockdown came into effect, and because of this he says he has now got to know himself and his colleagues better than he could have anticipated.

“Working remotely has given me greater appreciation and understanding of their home life, personal priorities and challenges. I have also seen how my colleagues handled the pressures of the pandemic to find solutions to brand new challenges, motivated by their passion for protecting patients and improving the way they live their lives.”

Belson says that the obvious place for GSK to start in its response to the pandemic was to leverage its experience in vaccine discovery.

“This specific vaccine effort, however, is like no other in its sense of urgency and scale of need,” he says. “With COVID, even the approach to vaccine discovery is transforming.

“The key word from the beginning has been ‘collaboration’,” he adds.“We are working in partnership with companies and research groups across the world to help accelerate the global effort to develop a vaccine to protect as many people as possible from COVID-19.”

“This specific vaccine effort, however, is like no other in its sense of urgency and scale of need. With COVID, even the approach to vaccine discovery is transforming”

He highlights GSK’s “unprecedented” partnership with Sanofi, where the two companies are combining their science and technologies to develop an adjuvanted COVID-19 vaccine, which entered clinical trials in September 2020.

But he stresses again that this collaborative effort needs to extend beyond the research and discovery phase.

“We are already thinking of how we will make a potentially successful vaccine candidate available and affordable globally, and in the UK we have already agreed with the government to supply up to 60 million doses of a COVID-19 vaccine.”

Beyond the urgent need for treatments and vaccines, the pandemic has also challenged the NHS to adapt quickly to establish new ways to keep patients, especially those most vulnerable to the virus, away from hospitals and clinics and remain in the safety of their own homes.

“We’ve also had to ask ourselves how we can support the NHS to meet those demands, working as a partner to protect the public,” says Belson. “This will only become more vital as we enter the latter months of the year and support the NHS as they attend to the backlog of patients that await non-COVID related examination and treatment and as they prepare for winter, which will bring additional pressures to the system, with the flu season upon us.”

One approach GSK has taken is to leverage its experience through a series of webinars that aim to support HCPs to build their skills and confidence as they take consultations online.

“This not only protects vulnerable patients but also our vital NHS workforce, reducing their exposure to the coronavirus and maintaining their ability to remain at work,” says Belson.

GSK has also started to pool knowledge into an accessible online resource hub, with the aim of creating a “one-stop shop” of guidance and support for respiratory HCPs across the NHS.

This provides free advice and training to support HCPs as they adjust to new tools and ways of working, and to guide respiratory patients through the journey with them.

The company is also contributing to the NHS’ ‘Your Covid Recovery’ online tool as patients return home to recover from the coronavirus.

“Severe asthma, lupus and cancer patients have been able to follow government guidance to reduce their exposure to COVID-19 by receiving care and testing in their homes,” says Belson. ”We’ve brought forward formulations for self-administration by working closely with regulatory bodies, as well as doubling homecare offerings and launching a patient app.

“These initiatives share an underlying factor: the use of innovation to improve people’s lives in these new circumstances and beyond.”

Patients aren’t just vulnerable during a pandemic, and Belson says that much of the novel approaches companies have tried in the past months will continue to be present and further evolved in the future.

“The NHS has provided an incredible level of care and support during this time, demonstrating the solutions our unique healthcare system can offer patients and HCPs.

“By giving severe asthma patients the independence to access their treatment from their sofa, we are freeing up time that HCPs can spend seeing and treating new patients on waiting lists in clinics. By those with respiratory and autoimmune diseases being able to see their GP on a screen and not through a waiting room, we are protecting them from unnecessary exposure to disease and complications. These are the types of solutions we will try to explore and support as the pandemic continues, working as a trusted partner alongside the NHS and patients.”

Belson says that the pandemic has emphasised the importance of asking ‘how’ care is administered as well as ‘what’ care is administered.

“We now need to continue working with our partners to benefit patients long-term.”

This series is supported by the Association of the British Pharmaceutical Industry (ABPI)

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FDA gives COVID-19 vaccine ‘advice’ after White House blocks guidance

The FDA may have been blocked from issuing stricter guidelines for emergency approval of COVID-19 vaccines by the Trump administration, but it has still managed to make its new approach public.

The regulator published “advice” to vaccine developers as part of documentation prepared for a vaccine advisory panel scheduled to convene later this month.

The five-page document sets out the information the FDA wants to see on safety and effectiveness and chemistry manufacturing and controls (CMC), and represents a tightening of the criteria for an emergency-use authorisation (EUA).

For example, the agency wants to see median follow-up duration of at least two months after completion of the full vaccination regimen in phase 3 studies – which would make it almost impossible for a shot to get the green light before the US election given that the front-runner jabs require two doses given at least 3-4 weeks apart.

The Trump Administration blocked the FDA from introducing new guidelines because they would set back the timeline for a COVID-19 green light by several weeks, scuppering the President’s plans to get a shot available before Americans go to the polls on 3 November.

Trump has also accused the FDA of succumbing to political pressure to delay approval of a vaccine, which the agency denies, and says industry had objected to the tougher standards. That prompted this response from former FDA Commissioner Scott Gottlieb:

Consumer group Public Citizen meanwhile said today that the suppression of the FDA guidelines “represents the latest but most dangerous politicisation of the US public health response to the catastrophic pandemic.”

There has been speculation for some weeks that the Trump administration could try to authorise a vaccine without oversight from the FDA, and the agency’s decision to set out its criteria publicly suggests it is resisting any such move.

Trump has previously said that a vaccine may be available this month, and the administration has pledged to provide tens of millions of doses before the end of the year.

Michael Carome, director of Public Citizen’s Health Research Group, said that the interference from the White House is an “appalling action that will only feed public distrust in any future COVID-19 vaccine marketed under an EUA, fostering vaccine hesitancy and prolonging the pandemic.”

Industry is also concerned. Just last week, the BIO trade organisation sent an open letter to Health & Human Services Secretary Alex Azar asking that all new guidance developed by the FDA concerning EUA for vaccines to prevent the spread of COVID-19 be released.

“The…guidance would provide scientists and researchers greater regulatory clarity and strengthen public confidence in any future vaccine that may be authorised or approved,” said the letter, signed by BIO chief executive Michelle McMurry-Heath.

The current FDA Commissioner Stephen Hahn has previously insisted that the agency will not be swayed by political pressure during presidential election campaigning.

The FDA guidelines reportedly also envisage that an independent advisory committee should be convened to go over the data before it can consider EUA. With the election now less than a month away, the timeline for setting up and running an advisory committee would also make it highly unlikely that a vaccine could be available before then.

Among the leading vaccines, Pfizer/BioNTech’s RNA-based candidate looks like it is the only one with a chance of seeking an EUA ahead of the election. Moderna has said it doesn’t expect results with its RNA shot until later that month, while AstraZeneca’s adenoviral-based vaccine is still on clinical hold in the US.

The latest twist in the coronavirus vaccine story comes during another politically fractious week in the coronavirus fight, with Trump now back at the White House after contracting COVID-19.

He immediately courted controversy by downplaying the seriousness of the virus, removing his face mask while posing for pictures despite still being infectious, and claiming that vaccines are “coming momentarily.”

Meanwhile, Facebook has deleted a post in which Trump had claimed COVID-19 was “less lethal” than the flu, placing it behind a warning about “spreading misleading and potentially harmful information.”

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Why intelligent automation is the future for regulation

There are a host of new, previously unimaginable tools and techniques – from analytics to robotic process automation (RPA) and artificial intelligence (AI) – available to help speed up processes and increase data accuracy. But for many life sciences organisations, these tools are either not yet fully adopted or are not being put to good use within their regulatory functions.

In Accenture’s Intelligent Life Sciences: Redefining Regulatory through Intelligent Automation report, we underscore how automation can help regulatory professionals in life science organisations bring products to patients faster.

Adopting intelligent automation could help organisations realise disruptive benefits that are above and beyond the tangible gains of cost, quality and productivity improvements. By applying intelligent automation, companies could realistically expect to enable: the seamless distribution of product information in a variety of multimedia channels to all internal and external stakeholders; rapid and accelerated implementation of product advances that could propel continuous improvement; and advanced prediction of risks to mitigate against resource capacity constraints – which have been highlighted during COVID-19.

For many companies, it could be realistic to automate as much as half of the manual maintenance tasks currently performed, resulting in significantly different future operating models where blended roles will prevail with strategic product oversight.

“One of the most common mistakes companies make is to allow business units to carry automation initiatives in silos”

But where to begin?

Where do you begin this transformation? Start with the data. Companies need to change the way people collect, curate, interpret and apply data for regulatory submissions and improve confidence in that data. According to Accenture research, most organisations are still struggling to understand the basic ‘truth’ of the data they use and exchange with others. The Accenture Technology Vision survey found just one-third of 103 life sciences executives have high confidence in their data and validate it extensively. To improve data confidence regulatory executives should take a four-step approach to change how they:

  1. Collect Data: Life sciences organisations should utilise cloud-based solutions with global access that facilitates one repository with a single source of truth and eliminates the use of local file sharing and servers. By integrating applications across the end-to-end value chain, they eradicate data entry duplication.
  2. Curate Data: Regulatory specialists need to apply data standardisation and master data management to define the right granular level of data for storage. This needs to be done up front. By implementing robust data governance and management, they can maintain data quality and integrity. By ensuring traceability of data evolution, as well as end-to-end transparency of submission status and its components, they help promote confidence in the data itself.
  3. Interpret Data: Executives need to make more use of readily available data to drive business decisions and optimise operations. They should be applying analytics to past submission data to recommend future submission content plans and pre-empt and mitigate health authority (HA) questions.
  4. Apply Data: Regulatory employees should be using stored data to intelligently create submission documents. By limiting documents full of free text fields and subjectivity companies can adopt a more digitised approach, where document templates can be compiled automatically from available data. Making real-time data accessible to the consumers of the information when and where it’s needed increases the likelihood of buy-in to the system’s value-add. In this way, manufacturing scheduling can be optimised, and batch release decisions more informed. This, in turn, enables healthcare practitioners to get the most up-to-date product information at their fingertips.

Focusing on the business outcomes of how data can be interpreted and applied, through implementation of analytics, RPA and AI, will help strengthen your data vision, enhance your data stewardship culture and provide financial justification for investing in improved data management. This is crucial because all signs point to a future world order of increasing volumes and complexity of new products coming to market, and digital support is a must have – not a nice to have – to handle this workload.

What intelligent automation to consider?

As companies make the move into the realms of intelligent automation, there are 3 key considerations that need to be considered from the offset.

  1. Set the North Star vision: Discuss the company strategy and pipeline considerations for the next 3-5 years and what the business objectives to achieve this strategy are. Is the driver for intelligent automation waste reduction and cost saving, or the speed at which innovative products are being brought to patients? Define the priority focus areas for your intelligent automation roadmap and evaluate the balance of ‘quick wins’ versus longer term strategy initiatives.
  2. Create the Operational Blueprint: Outline what the future processes look like with the inclusion of intelligent automation. What activities remain and from where should they be performed? Consider how job descriptions and roles will evolve to account for the transformed future working environment.
  3. Prototype, automate, evaluate, repeat: Establish the infrastructure to prototype at speed and fail fast. Consider how to implement in an agile, modular manner that gradually combines into an end-to-end solution. Carefully evaluate benefits realised.
“Lack of communication on how the workforce will be re-purposed post automation implementation can lead to internal unrest and possible attrition”

Here are some example use cases showing how Intelligent Automation is changing the game:

Regulatory Requirements & Content Plans

  • Business Challenge: Maintaining data on submission requirements is a constant challenge. As a result, market requirements gathering is often repeated for each submission, generating longer lead-times. Additionally, insights gained from HA feedback are not incorporated into submissions, reducing first time submission approval accuracy.
  • Solution: Analytics can compare new submission properties against past submissions to suggest a content plan based on the closest match, and most recent, approved submission.

Health Authority Correspondence Processing

  • Business Challenge: Timely recording of submission approval dates or tracking of HA questions can be challenging when information received by affiliates needs deciphering and translating before being entered into regulatory systems.
  • Solution: AI tools can translate and decipher letters without the need for local affiliate intervention and automatically enter information in Regulatory Information Management systems for stakeholders to act upon.

Label Authoring and Tracking

  • Business Challenge: Managing and providing traceability of the roll out of global label updates is onerous based on language nuances, implementation considerations and replicated data terms across multiple documents which can lead to a high risk of product label inconsistencies.
  • Solution: AI tools can take the complexity out of mapping global-to-local terms and automatically suggest what updates are needed where, as well as provide end-to-end traceability of the update progress.

As companies make the move to adopt intelligent automation, they need to make sure their projects are: business-outcome oriented (rather than simply automating a task or function); human-centred (so they don’t just eliminate repetitive tasks but rather free up people to focus on higher-value analysis, decision making and innovation); and technology rich (i.e. integrated into the broader architecture of data sources and applications).

How do you ensure success?

And there are pitfalls to avoid. One of the most common mistakes companies (across all industries) make is to allow business units to carry automation initiatives in silos. You should drive home the notion of ‘one company’ and keep an eagle-eye out for cowboys building their own rogue programmes. Similarly, make sure everyone is on the same page – if there is a disconnect between IT and the business, what’s built may not serve what’s needed. And make sure your HR, training and communications teams are looped in, informed and armed with the right information and tools to encourage and support adoption.

Lack of communication on how the workforce will be re-purposed post automation implementation can lead to internal unrest and possible attrition. There will need to be training and change control in place, and that takes planning and management. Finally, from the onset and throughout there needs to be a team tasked with ensuring responsible automation is in place. This needs to be owned by the C-Suite and at every turn communicated to employees, so it is part of the DNA of the transformation: consider the ethical and legal implications when data is handled, and tasks are automated. Know who is accountable and responsible for outcomes and ensure those teams own that responsibility.

The process of adopting intelligent automation isn’t easy but it’s also unavoidable. Adoption of processes and procedures to handle complex data is essential in this day and age – the companies that fail to build a platform that is adaptable to change are at risk of being left behind; those that do adopt new solutions are not only poised to succeed – they are the industry leaders of the future.

About the author

Kim BrownriggKim Brownrigg is a senior principal at Accenture and leads the Regulatory Domain in Europe. Her responsibilities include interlinking Consulting, Technology and Operations services to optimise client value and defining next generation service offerings. Kim is currently leading Accenture’s Regulatory digital transformation programme; helping clients define their digital strategy and roadmap within Regulatory, designing applied intelligence solutions and prototypes and delivering pilots and scaled implementation to transform and streamline the industry.

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Older people first to receive COVID-19 vaccine in UK, says government

As European regulators begin a rolling review of AstraZeneca’s COVID-19 vaccine, the focus in the UK has shifted to the government’s plans to distribute any vaccine that is deemed to be a safe and effective way of preventing the disease.

According to weekend press reports a rollout of a vaccine could be just three months away – but the feedback from the government is that not everyone will get it, with the target group being around 30 million older people and health workers, less than half the population of 67 million.

Speaking to the Financial Times, the head of the country’s coronavirus vaccine task force Kate Bingham said that any vaccination programme will be targeted at the most vulnerable in society.

She said: “People keep talking about ‘time to vaccinate the whole population’ but that is misguided.

“There is going to be no vaccination of people under 18. It’s an adult-only vaccine for people over 50 focusing on health workers and care home workers and the vulnerable.”

The strategy will likely be based on a draft list published last month by the government’s Joint Committee on Vaccine and Immunisation (JCVI), showing who is likely to be first to receive the vaccine.

According to the JCVI a “simple age-based programme” will decide who gets priority, as this will allow the vaccine to get to those at highest risk at the fastest possible speed.

Older adults in care homes and care home workers would be in the first group, followed by those aged over 80, over 75, over 70 and over 65.

A sixth priority group would comprise of younger adults under 65 with conditions that leave them at high risk of developing serious complications from the virus.

They would be followed by those aged under 65 who have a moderate risk level.

Even distributing the vaccine to half the population will be a major logistical challenge, however, and the UK government is facing scrutiny and criticism over its handling of the pandemic so far.

Flaws in the coronavirus reporting system emerged over the weekend when it emerged that nearly 16,000 cases had been missed in daily figures over the last week or so because of an IT error.

The government has also been criticised for failing to implement a track and trace system early in the pandemic, a measure that limited its spread in other countries.

Health secretary Matt Hancock has already said that the military may be brought in to help distribute the vaccine.

Getting what could be the final stage of the fight against COVID-19 right will be vital if the government wishes to restore credibility, as millions continue to live under lockdown restrictions that have cost thousands of jobs and continue to damage the economy.

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EMA starts rapid review of Bluebird’s gene therapy for rare disease CALD

Bluebird bio could be just a few months away from approval of its gene therapy for rare disease cerebral adrenoleukodystrophy (CALD) in the EU, after the EMA started an accelerated review.

If approved, Lenti-D (elivaldogene autotemcel or eli-cel) could transform the prospects of people with CALD, the most severe form of the neurodegenerative disease ALD that usually emerges in boys during early childhood and causes physical and mental disabilities as well as behavioural problems.

Around 40% of patients develop the cerebral form of ALD, which in turn affects around one in 17,000 live births.

A few weeks ago, Bluebird reported new data from the phase 2/3 STARBEAM trial of Lenti-D which showed that 87% of CALD patients were still alive and free of major functional disabilities after at least two years’ follow-up.

The EU filing comes ahead of a filing for eli-cel in the US, which Bluebird says should take place sometime towards the middle of next year, having been delayed by the coronavirus pandemic.

If approved, eli-cel would provide a one-shot treatment for CALD, holding back the progressive breakdown in the protective myelin that sheathes neurons.

It would be the first alternative to a stem cell transplant to treat the disease, a therapy that can provide significant improvements and even halt progression in some patients if given early enough.

However it requires high-dose chemotherapy to destroy the bone marrow, and that poses significant risks to patients in its own right, and can also lead to graft-versus-host disease, a potentially life-threatening complication in which the bone marrow donor’s immune cells attack the recipient’s cells and tissues.

CALD is caused by mutations in the ABCD1 gene located on the X chromosome, which provides instructions for the production of the ALD protein.

ALD protein is needed to clear toxic molecules called very long-chain fatty acids (VLCFAs) in the brain, and if mutated causes the VLCFAs to accumulate and damage the myelin sheath.

Using eli-cel, the patient’s own stem cells are modified in the lab to produce a working version of the ABCD1 gene, producing functional ALD protein that can help to flush VLCFAs from the body.

“CALD is a devastating disease, often marked by rapid neurodegeneration, the development of major functional disabilities, and eventual death,” said Gary Fortin, head of severe genetic disease programmes at Bluebird.

“If approved, eli-cel would represent the first therapy for CALD that uses a patient’s own haematopoietic stem cells, potentially mitigating the risk of life-threatening immune complications associated with transplant using cells from a donor,” he added.

Aside from STARBEAM, which will follow treated patients for up to 15 years, Bluebird is also conducting the phase 3 ALD-104 trial of eli-cel in CALD, which is due to generate results in 2024.

The EU filing for eli-cel comes shortly after Bluebird’s development partner received a 27 March 2021 FDA review date for anti-BCMA CAR-T cell therapy ide-cel, a potential therapy for multiple myeloma.

The biotech already has approval in Europe for Zynteglo, a gene therapy for haematological disease beta thalassaemia, and is due to file its related therapy LentiGlobin for sickle cell disease next year. The two therapies have been tipped to generate $1.5 billion-plus in peak sales by some analysts.

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FDA hands Cassiopea its first approval, for acne drug Winlevi

Italian biotech Cassiopea has won US approval for Winlevi, a topical therapy it says is the first new approach to treating acne in nearly 40 years.

An androgen receptor inhibitor, Winlevi (clascoterone) has been cleared by the US regulator for the treatment of acne in patients 12 years and older and is due to be launched early next year, according to the company.

Shares in dermatology specialist Cassiopea, which is listed on the SWX exchange in Switzerland, rose almost 17% after news of the FDA approval emerged.

There are an estimated 50 million people with acne in the US, mostly adolescents, with around one in five having severe acne that can result in permanent physical scarring as well as emotional problems.

Current treatments are dominated by generic drugs, and include topical antiseptics, retinoids which work by removing dead skin cells from the surface of the skin but can cause pain and inflammation, and topical antibiotics, as well as hormonal therapies including oral androgen inhibitors like spironolactone or cyproterone.

Cassiopea claims that a drug that works by inhibiting androgen hormones in the skin is “game-changing” as it tackles aspects of acne not addressed by other drugs, and limits the systemic side-effect issues that limit the use of oral alternatives.

Retinoids can help unclog pores, while antibiotics can limit the growth of bacteria. By locally blocking androgens, Winlevi prevents the production of excess oil (sebum) and dampens down inflammation, according to the company.

In trials, twice-daily clascoterone was able to reduce inflamed spots and non-inflammatory lesions like comedones  (blackheads or whiteheads) more effectively over 12 weeks than a control cream, and was well-tolerated with side effects similar to placebo.

The commercial prospects for Winlevi are hard to gauge, as the current drugs used to treat acne are all very cheap, but the overall market represents multibillion dollars per year, and Cassiopea’s drug could end up being used alongside current treatments as acne is a multi-faceted condition.

The biotech isn’t revealing how much it intends to charge for the new medicine, saying it will do so closer to launch later this year.

Dermatologists expect brisk take-up among people who struggle to get a benefit from current treatments, and analysts at Jefferies have previously said they see “substantial commercial potential” for Winlevi which could provide the foundation for a “highly profitable US dermatology franchise.”

Cassiopea is also developing clascoterone as a topical solution for hair loss in men and women, which could also be a big market opportunity if planned phase 3 studies are successful, and has an immune modulator drug for genital warts in mid-stage testing.

Cassiopea spun out of Ireland-domiciled Cosmo Pharma in 2015.

Photo by Scott Webb on Unsplash

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Teva charged in US price-fixing investigation

The US Department of Justice has charged Teva with conspiring with other pharma companies to fix prices for generic drugs.

According to an indictment filed on Tuesday, the company participated in three counts of conspiracy from at least May 2013 until around December 2015, which could have resulted in customers being overcharged by at least $350 million.

The Department alleges that Teva conspired with companies including Sandoz, Glenmark Pharmaceuticals, Apotex and Taro USA to increase prices, rig bids, and allocate customers for generic drugs including medicines for arthritis, brain cancer, cystic fibrosis, seizures, pain, skin conditions, and blood clots, as well as the cholesterol medicine pravastatin.

Sandoz, Apotex and Taro USA have admitted to their roles in these conspiracies and agreed to pay fines. Glenmark is awaiting trial.

Four pharma company executives have also been charged, three of whom have entered guilty pleas. The fourth, Apotex’s former executive Ara Aprahamian, is awaiting trial.

Each of the charged offenses carry a statutory maximum penalty of $100 million for companies, but the maximum fine may be increased to twice the gain derived from the crime or twice the loss suffered by the victims if either amount is greater than $100 million.

“Today’s charge reaffirms that no company is too big to be prosecuted for its role in conspiracies that led to substantially higher prices for generic drugs relied on by millions of Americans,” said assistant attorney general Makan Delrahim of the Department of Justice’s Antitrust Division.

“The division will continue to work closely with our law enforcement partners to ensure that companies that blatantly cheat consumers of the benefits of free markets are prosecuted to the full extent of the law.”

In a statement Teva said it was “deeply disappointed” that the government had chosen to proceed with this prosecution.

“The Company has been investigating this matter for over four years and has concluded that Teva did not participate in price fixing,” it said. “Based on our internal review, Teva firmly rejects the allegations and will vigorously defend the Company in court.

“Teva has fully cooperated throughout the course of the Department of Justice (DOJ) investigation and has attempted to reach a resolution in the best interest of the Company, its stakeholders and the patients the company serves. The DOJ has shown an unwillingness to consider alternatives that would not deeply impact Teva and the stakeholders who depend on the Company, including the patients who benefit from our medicines.”

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COVID plasma treatment gets emergency license from FDA after Trump criticism

The FDA has allowed a blood plasma treatment for COVID-19 to be administered under an Emergency Use license – but some have decried the move as a “political stunt” as president Trump accuses the agency of impeding progress on coronavirus therapies.

The convalescent plasma treatment involves giving COVID patients antibody-rich blood plasma from people who have already recovered from the disease.

It has already been used on over 70,000 people in the US under an Expanded Access Program launched in April, which opened up use to patients who were seriously ill or involved in clinical trials, and now the agency has given it an Emergency Use License while clinical trials remain ongoing.

The FDA said that, based on early data from an analysis of 20,000 patients who received this treatment, it is “reasonable to believe” that COVID-19 convalescent plasma may be effective in lessening the severity of the illness in some hospitalised patients. 

The agency added that the known and potential benefits of the product when used to treat COVID-19 outweigh the risks, and that there are no adequate, approved, and available alternative treatments.

But experts have questioned whether there is really enough data to show that the treatment is safe and effective – especially as the announcement came only a day after president Trump accused the FDA of deliberately impeding progress on COVID-19 treatment and vaccines until after the US election on 3 November.

“Convalescent plasma may have some efficacy, but we need to have definitive data and tonight’s EUA was clearly a political stunt,” Jonathan Reiner, a professor of medicine at George Washington University, said on Twitter.

Meanwhile, the Infectious Diseases Society of America said in a statement that “we lack the randomised controlled trial data we need to better understand [convalescent plasma’s] utility in COVID-19 treatment”.

However, Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research said the agency was “comfortable” with the data and that they “continue to see no concerning safety signals.

“I am committed to releasing safe and potentially helpful treatments for COVID-19 as quickly as possible in order to save lives,” added  FDA Commissioner Stephen Hahn. “We’re encouraged by the early promising data that we’ve seen about convalescent plasma. The data from studies conducted this year shows that plasma from patients who’ve recovered from COVID-19 has the potential to help treat those who are suffering from the effects of getting this terrible virus.

“At the same time, we will continue to work with researchers to continue randomised clinical trials to study the safety and effectiveness of convalescent plasma in treating patients.”

In April a group of companies that specialise in plasma-derived drugs announced that they will pool their resources to try to develop an “unbranded” hyperimmune immunoglobulin drug for SARS-CoV-2, the virus that causes COVID-19.

Led by Takeda and CSL Behring, the consortium also includes Biotest, BPL Group, LFB and Octapharma.

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Mission successful for Novartis after FDA approves ofatumumab in MS

It’s mission accomplished for Novartis after the FDA approved ofatumumab for multiple sclerosis, completing a project where the former cancer drug has been repurposed.

The FDA approved ofatumumab under the brand name Kesimpta for people living with relapsing forms of multiple sclerosis.

Kesimpta will have a list price of around $83,000 a year, which the company argues will make it one of the lowest-cost branded options in a highly competitive market where drugs like Sanofi’s Aubagio and Roche’s Ocrevus have strong footholds.

Novartis is also talking up Kesimpta’s “favourable” safety profile and an injector pen that allows the drug to be administered each month at home.

The company hopes this will give it a competitive advantage over Roche’s Ocrevus (ocrelizumab), which is given as an infusion every six months in a hospital clinic after two starter doses two weeks apart.

Novartis also pointed to trial data showing better efficacy and similar safety profile when compared with Sanofi’s oral MS drug Aubagio (teriflunomide).

Ofatumumab was first approved by the FDA as a cancer drug in chronic lymphocytic leukaemia (CLL), under the brand name Arzerra, in 2014 when it was owned by GlaxoSmithKline.

But Novartis took control of ofatumumab in 2015 as part of an asset-swap deal, picking up rights to its other uses in autoimmune diseases such as MS, and has completed a research project lasting around 10 years to reimagine the drug as a treatment for MS.

Patients taking the drug for CLL in the US will be transitioned over to an access programme at no cost.

Novartis will pay co-developer Genmab a lump sum of $30 million as payment for lost royalties.

Kesimpta works by targeting B-cells, which are the underlying cause of both multiple sclerosis and several kinds of blood cancer including CLL.

Approval of Kesimpta is based on results from the phase 3 ASCLEPIOS I and II studies, in which it demonstrated superiority versus Aubagio in significantly reducing the annualised relapse rate, three-month confirmed disability progression, and the number of gadolinium-enhancing T1 and new or enlarging T2 lesions.

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NICE recommends regular NHS funding for Roche’s lymphoma drug Polivy

NICE has recommended regular NHS funding for Roche’s Polivy in certain lymphoma patients in final draft guidance, overturning a previous rejection.

The new guidance recommends Polivy (polatuzumab vedotin) in combination with rituximab and bendamustine, for adults with diffuse large B-cell lymphoma (DLBCL), in second line when patients cannot have a stem cell transplant.

Around 4,800 people in England have DLBCL and around 530 of these will be eligible for the treatment.

NICE had rejected the treatment in previous draft guidance, but Roche has since offered an “updated commercial agreement” – likely a further confidential price cut – and offered further analyses relating to long-term survival data.

This has swayed NICE, which says it considers Polivy to be a cost-effective use of NHS resources.

NICE cited clinical trial evidence showing that in 40 patients treated with Polivy combination it caused cancer to become undetectable in around 40% of the cohort, compared with around 18% of the 40 patients treated with rituximab and bendamustine alone.

While NICE conceded there is uncertainty in the long-term data on remission, the evidence also suggested the combination treatment may increase progression-free survival and overall survival compared with rituximab and bendamustine.

DLBCL accounts for two in five non-Hodgkin’s lymphoma (NHL) cases in the UK. It is an aggressive disease that progresses rapidly, with a significant negative impact on the quality of life of patients.

Delivered intravenously every three weeks, the average cost of a course of the combination treatment is £50,416 at its list price, but the company offered the NHS a confidential discount.

Final guidance is expected to be published next month.

Pia Ballschmieter, haematology franchise lead, Roche Products Limited said: “People with relapsed or refractory diffuse large B-cell lymphoma have limited treatment options, especially those who are not candidates for haematopoietic stem cell transplant.

“We are proud to have collaborated with the clinical community and NICE to ensure that, from now on, people are able to benefit from Polivy, which represents a step forward in the treatment of this disease.”

Polivy is a first in class antibody drug conjugate, which targets the CD79b protein expressed on the majority of B-cells that cause NHL.

It binds to CD79b and delivers a cytotoxic agent resulting in cell death.

 

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Coronavirus pharma news roundup – 14/08/20

Catch up on the latest coronavirus vaccine and digital tech news in our roundup of this week’s biggest stories.

  • Consumer advocacy group Public Citizen has slammed the amount Moderna is charging the US for the mRNA-1273 vaccine, saying that as taxpayer money had funded 100% of the work done to bring it to market the US is “paying twice” for the shot. The US has signed a deal for 100 million doses of the jab for a little over $1.5 billion – around $15 per dose or $30 per course, a steep discount on the $32 to $37 price per dose in its earlier smaller deals.
  • Russia has become the first country in the world to approve a coronavirus vaccine, amid scepticism from international experts who have been unable to review or verify clinical data from the jab called ‘Sputnik V’.
  • Swiss medical data specialist Sophia Genetics has launched an AI platform that will sift through data generated at more than 1,000 hospitals around the world to try to work out how the COVID-19 pandemic will evolve in the coming months and years.
  • The UK is to buy millions more doses of potential coronavirus vaccines from Johnson & Johnson and Novavax, with the latter expanding its manufacturing operation in the country.
  • Pfizer has signed a multi-year agreement with Gilead to manufacture and supply the COVID-19 antiviral remdesivir, which is also being tested in combination with other drugs in an effort to fight the pandemic.
  • Novavax’s COVID-19 vaccine produced higher levels of neutralising antibodies than produced by recovered patients in an early trial, paving the way for a phase 3 trial and potential approval by year-end.
  • The NHS is on the hunt for digital pioneers to reshape services during the pandemic. London has opened applications to its Fellowship programme, supporting change makers employed by NHS organisations in London to design and lead transformation projects underpinned by digital innovation.
  • Drugmakers have been working with data specialist Certara on a new tool that they hope could speed up the development of vaccines for COVID-19. The new “biosimulation” tool is designed to make it easier for vaccine candidates across multiple patient populations through the use of virtual patients and trials, providing insights before any real-life studies have to be carried out.
  • Just under 6% of England’s population – around 3.4 million people – had been infected with coronavirus by the end of June according to an estimate based on antibody tests.
  • After ditching its home-grown attempt at a coronavirus contact-tracing app for smartphones, the UK is ready to start pilot trials of a second version based on a platform developed by Apple and Google.
  • A new digital therapy is aiming to tackle depression during the COVID-19 pandemic, using a brain stimulation headset and therapy app that claims to have similar beneficial effects to drugs but with fewer side-effects.

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J+D Forecasting strike the balance for the liquid tumour market

J+D Forecasting strike the balance between simplicity and complexity when modelling for the liquid tumour market

The Challenge

Identify a clear, transparent, and logical way to structure a forecast model to identify the potential for a new therapy in leukaemia.

The model would be complex because patients go through different stages of treatment within a single line of treatment (for example, induction chemo followed by consolidation chemo followed by maintenance therapy). In addition, not all patients will follow the same treatment pathway in any single line of treatment.

A new forecasting approach was required:

  • To instil confidence in the outputs for a go- or no-go decision
  • To incorporate changes in the flow of patients and eligibility for therapy
  • To handle the complexity of following patients within a line of treatment

In addition:

  • The model must be user friendly and intuitive
  • The model must incorporate a robust approach to risk analysis to support the decision
  • The approach must support best practice forecasting principles

Ideally the client team wanted to see a cost reduction vs. their current software.

The Approach and Solution

STEP 1: WORKSHOP

  • To clarify the challenges in detail
  • To meet the team and understand their individual needs
  • To identify business and department priorities
  • To explore the data available and the specific outputs the team sought

STEP 2: THE SCHEMATIC

  • J+D Forecasting created a schematic – a visual structure/layout of the model
  • The client reviewed and identified gaps they felt were important to how they and their colleagues would make a final decision to go/not go with the new therapy
  • This approach promoted team collaboration and understanding and buy in to the final model.
  • The schematic was finalised and signed off as part of J+D standard model development process.

STEP 3: SCOPING AND CREATION

Different forecasting methodologies were considered such as a standard epi cross sectional. However, the team settled on a patient flow approach. The patient flow methodology was considered essential as this is the only forecasting approach that allows you to ‘follow’ patients through their treatment journey.

This is a more accurate approach to defining the size of the potential patient pool and therefore, size of potential opportunity for the leukaemia therapy under exploration.

A forecast model structure was created using Onco+, an Excel add-in created by J+D Forecasting. Onco+ is based on a patient flow methodology created to incorporate all the Oncology variables that affect the forecast. For example, stages/regimens/lines of therapy, restrictions, length of therapy, holidays periods, wastage and has a variety of conversion options too.

The therapy, although likely to be approved for late stages, was likely to be approved for earlier stages in the future. Onco+ helped the team evaluate several potential scenarios for up to 3 lines of therapy.  It also provided the outputs that the client was looking for (patients, units, packs, gross revenue and net revenue – all by SKU) using a conversion approach that closely matched the reality of the market that was being forecast.

The Result

The product is yet to be launched and further exploration is underway after roll-out of Onco+ across multiple departments within the organisation.

Onco+ has provided a balance of the necessary complexity with the appropriate level of simplicity to be usable and transparent across the organisation.

J+D’s approach and the model has given the team greater confidence in the outputs and subsequent decisions they will have to make in taking the product forward.

Learn more on the J+D Forecasting website

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Regeneron’s cholesterol drug evinacumab claims February FDA date

The FDA has started a speedy review of Regeneron’s ANGPTL3-targeting antibody evinacumab for a rare, inherited disorder that dramatically raises the risk of heart disease.

The cholesterol-lowering drug has been classed as a breakthrough therapy for homozygous familial hypercholesterolaemia (HoFH) by the FDA, which is due to deliver a decision on the marketing application by 11 February after a truncated six-month review.

HoFH affects around 1,300 people in the US, says the biotech, and raises cholesterol levels in the blood to very high levels. As a consequence, people with the condition can develop cardiovascular disease very early, even in childhood in some cases, despite aggressive treatment with cholesterol-lowering drugs like statins and PCSK9 inhibitors.

Evinacumab (formerly REGN1500) was developed after scientists discovered that people with genetic profiles that reduced ANGPTL3 gene activity had significant lower levels of LDL cholesterol, and a decrease in the risk of developing heart disease,

If approved, it will sit alongside Sanofi-partnered PCSK9 inhibitor Praluent (alirocumab) – which has underperformed since its launch in 2015 – in Regeneron’s emerging cardiovascular franchise.

The ANGPTL3 antibody has been filed for approval in the US and Europe on the back of the phase 3 ELIPSE trial, which tested the antibody in 65 HoFH patients already being treated with statins, PCSK9 inhibitors and other drugs like ezetimibe.

Adding in Regeneron’s antibody resulted in a 49% drop in cholesterol levels from the start of the study compared to patients sticking with their current therapy alone, according to results presented earlier this year at the American College of Cardiology’ congress in March.

The FDA awarded evinacumab breakthrough status in 2017 on the strength of phase 2 data which also showed that the antibody could achieve impressive 50% reductions in LDL cholesterol, as well as cutting blood lipids like triglycerides, in HoFH patients.

There’s no data showing that the drug can reduce progression to heart disease yet, but it’s widely believed that cutting blood lipids can reduce that risk.

Not all patients with HoFH are the same however as there are multiple genes involved in the disease, including those for LDL receptors, apolipoprotein B and PCSK9.

Crucially, Regeneron’s drug seems to work even in so-called ‘null-null’ patients, which have very low levels of receptors that remove LDL cholesterol from the blood and so progress to cardiovascular complications very quickly.

Evinacumab may not be so significant commercially however, at least in the near term, although it will likely be able to command higher pricing than Praluent due to the rarity of HoFH. Analysts put peak US sales in the region of $200 million to $400 million.

Once tipped as blockbusters, Praluent and a rival PCSK9 drug from Amgen – Repatha (evolocumab) – have struggled to gain sales momentum in the much larger population of people with other forms of high cholesterol, and have yet to crack the $1 billion sales threshold, even when their sales are combined.

They now also face the threat of competition from Novartis PCSK9 rival inclisiran, which offers much less frequent dosing.

Evinacumab is expected to be a smaller product, thanks to the tiny population affected by the ultra-rare indication, although Regeneron will be able to detail using the same salesforce that sells Praluent, reducing the cost of rollout if approved.

The biotech is also running trials that could end up expanding its use into patients with heterozygous familial hypercholesterolaemia (HeFH) – a less severe inherited disorder – as well as for patients with non-inherited forms of high cholesterol who can’t meet treatment targets with a statin and PCSK9 inhibitor.

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NS Pharma takes on Sarepta as FDA approves DMD drug

The FDA has approved a new therapy for the rare muscle wasting disease Duchenne muscular dystrophy (DMD) as Japan’s NS Pharma takes on Sarepta and its controversially approved rival.

NS Pharma’s Viltepso (viltolarsen) has been approved in patients who have confirmed mutation of the DMD gene that is amenable to exon 53 skipping.

The DMD gene is made up of 79 exons, and mutations in that code can result in a deficiency in dystrophin which is responsible for the muscle wasting in DMD.

Exon-skipping drugs are used to patch the mutations and allow the gene to produce partially functional dystrophin.

Viltepso can be used to treat around 8% of DMD patients and previously approved DMD drugs has not been shown to change the course of the disease.

However what it does do is help produce the dystrophin that patients with the disease are lacking.

It’s bad form to compare performance of drugs in separate clinical trials, but results suggest that Viltepso helps patients produce more dystrophin than Sarepta’s rival Vyondys 53 (golodirsen).

The FDA controversially approved Vyondys 52 late last year after a previous rejection and an appeal from Sarepta.

Viltepso was evaluated in two clinical studies with a total of 32 patients, all of whom were male and had genetically confirmed DMD.

The increase in dystrophin production was established in one of those two studies, a study that included 16 DMD patients, with 8 patients receiving Viltepso at the recommended dose. In the study, dystrophin levels increased, on average, from 0.6% of normal at baseline to 5.9% of normal at week 25.

The FDA deemed that this increase in dystrophin production is “reasonable likely” to predict a clinical benefit –something that is difficult to measure in such a small study.

As part of the accelerated approval process, the FDA requires NS Pharma to conduct a trial to confirm clinical benefit.

This ongoing study will assess whether Viltepso improves the time to stand for DMD patients with the confirmed mutation.

If the trial fails to verify clinical benefit, the FDA may begin proceedings to withdraw approval.

The most common side-effects in the two trials were upper respiratory tract infection, injection site reaction, cough and fever.

There have been no signs of liver toxicity in the 80 patients treated so far, but the FDA is warning doctors to monitor renal function as this issue has been observed in patients taking antisense oligonucleotides.

 

 

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Anger at US deal for Moderna’s ‘taxpayer-funded’ COVID-19 vaccine

The US government has signed another big coronavirus vaccine supply deal, snapping up 100 million doses of Moderna’s mRNA jab for a little over $1.5 billion –around $15 per dose or $30 per course.

That’s a steep discount on the $32 to $37 price per dose in its earlier smaller deals, revealing that purchasing power will be a big factor as supplies of COVID-19 vaccines become available – and also that countries with deep pockets will be at the front of the queue.

Nevertheless, consumer advocacy group Public Citizen has slammed the amount Moderna is charging the US for the mRNA-1273 vaccine, saying that as taxpayer money had funded 100% of the work done to bring it to market the US is “paying twice” for the shot.

“When the president bragged on the campaign trail about his deal-making prowess, this isn’t what people had in mind,” said the organisation.

“It is absurd that Trump and [Health and Human Services Secretary Alex Azar] are touting $30 per course as a good deal for the American people, in light of the consistent and ongoing support from the US government towards mRNA-1273 research, development and manufacturing.”

The $1.525 billion order includes $300 million in incentive payments for swift delivery, in other words if the vaccine is approved for marketing or gets an emergency-use green light on or before 31 January next year.

It takes the total amount allocated to the vaccine by the US government to $2.48 billion, including $955 million previously awarded to Moderna to fund clinical development and manufacturing of mRNA-1273.

The shot is in a phase 3 trial called COVE which started last month with the help of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

Moderna has previously said it is on track to deliver up to 500 million doses per year, and possibly up to a billion doses per year beginning in 2021, thanks to a manufacturing collaboration with Lonza.

The company also has a large-scale fill and finish contract with Catalent’s biologics facility in Indiana, following $1.3 billion in funding from investors in a public equity offering in May.

Shares in Moderna spiked up around 5% on the announcement, but fell back just as quickly to end the day only fractionally up.

Analysts said the US deal could lead to others being signed quickly as other countries try to snap up available stocks, once again raising fears of “vaccine nationalism” that will leave lower-income countries at the back of the queue when it comes to access.

The US government previously signed deals – all for 100 million doses – of a vaccine from Pfizer/BioNTech at a cost of $39 per course, $21 per dose for a Sanofi/GlaxoSmithKline shot, and $10 per dose for a Johnson & Johnson candidate.

It also has deals in place to supply vaccines from Novavax and AstraZeneca/University of Oxford for 100 million doses at $16 and 300 million doses at $4, respectively.

“The Trump Administration is increasing the likelihood that the US will have at least one safe, effective vaccine by 2021,” said Azar in a statement.

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Chiesi’s flagship Fabry drug heads for FDA verdict in early 2021

The FDA has started its review of Israeli biotech Protalix BioTherapeutics and partner Chiesi’s Fabry disease therapy pegunigalsidase alfa, setting up a possible approval by 27 January.

The enzyme replacement therapy (ERT) – also known as PRX-102 – has been granted a priority review by the US regulator, and is the top prospect in Chiesi’s recently formed rare diseases division.

Fabry disease is a rare genetic disease caused by a deficiency of an enzyme called alpha-galactosidase A that causes a build-up of toxic metabolites that cause a range of symptoms including pain, gastrointestinal symptoms and kidney damage.

Like other ERTs, pegunigalsidase alfa is given via an intravenous infusion and works to replenish the levels of alpha-galactosidase A, but has been modified to stabilise the enzyme and may allow less frequent dosing.

If approved, pegunigalsidase alfa will compete with established ERT drugs like Sanofi Genzyme’s Fabrazyme (agalsidase beta) and Takeda’s Replagal (agalsidase alfa), as well as Amicus Therapeutics’ newer, orally-active drug Galafold (migalastat) which made its debut in 2018 and is designed to bind and stabilise the enzyme in the body.

Earlier this year, Protalix and Chiesi reported results from the phase 3 BRIDGE trial showing that a year’s treatment with pegunigalsidase alfa was well-tolerated and seemed to slow kidney disease progression more effectively than Replagal, whilst also reducing biomarkers of Fabry disease.

The trial wasn’t a head-to-head comparison of the two drugs, but charted the course of treatment with the new drug in Fabry patients who had previously been maintained on Replagal therapy.

The initial application with the FDA is for dosing of 1mg/kg pegunigalsidase alfa every two weeks, the same interval as Fabrazyme and Replagal.

In the meantime, Chiesi and Protalix are also conducting a phase 3 trial – called BRIGHT – to see if the efficacy of their drug is retained at a dose of 2mg/kg given every four weeks.

Market research firm Optima Insights has predicted that sales of Fabry disease drugs will more than double from around $1.8 billion last year to $3.8 billion by 2027, driven by new oral drugs such as Galafold as well as gene therapies that are still in clinical development.

It says ERTs will remain a key part of Fabry treatment, although the first generation drugs could start to see biosimilar competition in the intervening period.

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Novo Nordisk: Prevention, digital tools and collaboration to define the future of diabetes

In our latest UK Leaders article Pinder Sahota, UK general manager at Novo Nordisk, tells us how he hopes to bring the NHS and pharma together to improve outcomes in diabetes and other long-term conditions.

Though Novo Nordisk is perhaps not as much of a household name as other pharma companies in the UK, it has a huge presence in diabetes, with a bigger market cap than the likes of GSK and AstraZeneca – and UK GM Pinder Sahota is keen to shout about the organisation that he describes as a “sleeping giant”.

“Danish culture is very humble, but there’s a lot going for the company in terms of the culture, the way staff are treated, the profile of the company and the sense of purpose, so I’d love for more people to hear about us.

“Novo Nordisk is actually the only company I’ve worked at that regularly audits its culture. Every couple of years we’ll look at where we want it to be and whether we are achieving that.”

In particular, when coming into the company two and a half years ago, Sahota sought to build a culture that “liberates talented people to be able to work together to do great work”.

“There are more and more instances where pharma workers need to be multidisciplinary – so we want to enable fantastic teamwork as a core competency.

“We can use the NHS as an example – look at the multidisciplinary nature of surgical procedures, for instance; the way they have to work, the way they communicate, the way they get feedback, the way they audit their results. That’s what we want to inject into Novo Nordisk.”

“We’d like to get to a point where our treatment and prevention offering can be packaged together for the NHS – because both go hand in hand, alongside digital tools”

Collaborating to prevent diabetes

Sahota says that these kinds of multidisciplinary teams are vital in order to propel projects forward and achieve the changes they want to see happen – which is particularly pertinent when diabetes and related conditions continue to have huge, unsustainable impacts on healthcare systems.

“These are massive societal burdens on countries,” says Sahota. “Whilst our treatments will help manage symptoms – and maybe one day offer a cure – we also recognise that these are unsustainable chronic conditions for society. If you want to be a sustainable company – not necessarily in terms of the environment, but in terms of what you do for your communities – then you need to focus on prevention as much as treatment.”

Sahota says that Novo Nordisk wants to take a “holistic view” on prevention.

“The solution to obesity isn’t just ‘exercise more’. There are various triggers for why obesity happens, and more and more factors are starting to be understood. Some of it is lifestyle, some of it is emotional, some of it is genetic – which is why last January, the Royal College of Physicians recognised obesity as a disease.

“We need to understand those factors and de-stigmatise obesity, making sure we provide the right support to individuals who need it.”

The company is helming various prevention programmes, such as Cities Changing Diabetes – a global initiative where Novo Nordisk helps cities tackle the condition.

“We’ve got two such projects in the UK, in Leicester and Manchester,” says Sahota. “We bring together people from different parts of the city – everyone from the mayor to faith communities and sports clubs – to have a conversation around how we can stop the rise of diabetes in the city. How can they make people aware of the issue, access the right kind of facilities, eat the right kind of food? How can we get that message into communities? Those conversations weren’t being had before.”

Sahota hopes that the company will be able to do more with these initiatives over time, as well as collaborating more with the NHS on obesity.

“We’d like to get to a point where our treatment and prevention offering can be packaged together – because both go hand in hand, alongside digital tools.”

Sahota sits on the ABPI board and leads one of the Association’s workstreams on engaging with the NHS on collaborations.

He says the UK industry is keen to foster large scale collaboration with the health system and overcome the barriers to partnership that some NHS customers face.

“If we can do this, then we can successfully improve outcomes for patients, and it’s a win-win all around. We’re pushing that agenda, but I still think it’s not going at the pace that we would like within the NHS.”

Sahota says that there are several approaches the industry can take to improve this.

“One is engaging at the highest level within the NHS to extoll the value of collaborating. We also believe it will help if we can put in place frameworks for how we can collaborate. In addition, it’s important that we tap into groups like the Academic Health Science Networks.”

He adds that the industry needs to think more “through the NHS’ eyes”.

“For example, in the NHS Long Term Plan, chronic conditions are called out because aging populations tend to suffer from diseases that have co-morbidities. This is where the burden for the healthcare system is going to be as people grow older and live longer.

“The NHS has identified those issues, and if we look at it through their eyes we can focus and figure out how best to ease that burden. Then you can come up with optimal solutions – whether it’s highly effective treatments, digital solutions, or prevention programmes.”

Sahota adds that the NHS’ willingness to engage with pharma is also improving.

“It’s a lot better than it was 10 years ago,” he says. “Some of these collaborations have resulted in significant improvements for patients, and the NHS’ challenge has always been scaling that to bigger regional or national impact. For me, that pace of change isn’t fast enough, but luckily through the ABPI I can have dialogue with NHS leaders about how we accelerate that.”

Digital tools

Sahota is also optimistic that the COVID-19 pandemic will ultimately boost adoption of the digital technologies that can be vital to improving outcomes in diabetes, saying that the crisis has “removed a lot of the cynicism and pre-conceived barriers” around such devices.

“The pandemic has shown everyone how we can work very differently. In the NHS, we are seeing more investment in telehealth. Six months ago, people would have said that telehealth had limited value and wasn’t going to take off, that you need to be able to physically see patients to really understand their conditions.

“The view now is that even post-COVID-19, the majority of consultations will probably be done remotely. Our industry needs to consider what we need to do to make our products, and our services, fit that type of consultation.”

This will also mean the industry needs to think about how HCPs will want to interact with pharma companies.

“If they’re more comfortable doing virtual consultations with their patients, then maybe this is something our commercial teams need to be engaging in as well.

“That will fundamentally change the way we set up our commercial models, the role of our commercial teams, and the skills that they need to acquire – which is something that Novo Nordisk is working hard on.”

Sahota adds that if pharma is able to more easily connect with patients remotely, this would help improve remote diabetes management – which is becoming an increasingly important part of diabetes care for many patients.

“There are several examples of continuous glucose monitors that a patient wears – the most famous example being the FreeStyle Libre device that Theresa May uses. They sit on the skin, monitor glucose levels, and give the patient constant readings on their phone. And in some cases, HCPs could see those readings as well, if they have permission.”

Novo Nordisk is itself investing in such technology, and is aiming to introduce more  connected devices, such as digital insulin pens, in the future.

“When the patient takes an insulin shot with this pen, the information gets downloaded to an app on the phone, which tells the patient when they took the dose, and what dose they took.

“There’s no need to fill out paper diaries, which are easy to forget about. Now the physician can view all of that remotely, then guide patients over the phone on what they’re doing right or wrong.”

The other side to this, Sahota says, is thinking about how companies can provide more support so that patients can self-care at home as well.

“As aging populations, long-term conditions, and co-morbidities place a burden on the healthcare system, governments and health departments have to figure out how patients can self-care and manage at home. Digital tools and technology can support that.”

Again, the spectre of this burden is the main factor driving the NHS, Novo Nordisk and other pharma companies to innovate with a holistic, multi-disciplinary approach to treatment and prevention.

“As the NHS gets squeezed so will the healthcare industry,” Sahota says, “and that’s where companies will have to work hard to show the value our treatments can offer – as well as what we are prepared to do in terms of collaborations to improve patient outcomes, NHS productivity, and prevention of long-term diseases.”

About the interviewee

Pinder SahotaPinder Sahota has been general manager and corporate vice president, United Kingdom, at Novo Nordisk since March 2018 with responsibility for all operations. Pinder is also a member of the European management team. Pinder brings extensive business, commercial and leadership experience to Novo Nordisk from a variety of senior UK and European roles. He was responsible for developing the commercial & market development strategy for key brands across Europe in his role as senior vice president of market and commercial development for Europe at Smith & Nephew based in Baar, Switzerland.

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Roche takes on pricey rivals as FDA approves SMA drug

Roche is hoping to undercut hugely expensive rivals after the FDA approved its oral spinal muscular atrophy (SMA) drug Evrysdi (risdiplam).

Evrysdi is the third treatment approved for SMA, an ultra-rare muscle wasting disease that can begin in early childhood, after Biogen’s Spinraza (nusinersen) and Novartis’ Zolgensma (onasemnogene abeparvovec).

But Spinraza costs $750,000 in the first year of treatment and about half that price annually from then on.

Zolgensma costs about $2.1m for a single shot of the gene therapy, making it the most expensive drug in the world by many people’s reckoning, although the manufacturer argues this is justified given the costs of treating the condition in later life.

Roche has decided to price Evrysdi according to its weight, costing up to $340,000 per year, with the cost being under $100,000 annually for some younger patients.

While this is not cheap by anybody’s reckoning, Roche hopes that the less intimidating price tag, plus the patient-friendly oral administration method will give it a competitive edge.

The FDA approved Evrysdi for the treatment of spinal muscular atrophy (SMA) in adults and children two months of age and older.

Roche noted that Evrysdi showed clinically-meaningful improvements in motor function across two clinical trials in people with varying ages and levels of disease severity, including Types 1, 2, and 3 SMA.

Infants achieved the ability to sit without support for at least five seconds, a key motor milestone not normally seen in the natural course of the disease.

Evrysdi also improved survival without permanent ventilation at 12 and 23 months, compared to natural history.

A liquid medicine, Evrysdi is administered daily at home by mouth or feeding tube.

Evrysdi is designed to treat SMA by increasing production of the survival of the motor neuron (SMN) protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement.

Roche leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.

Evrysdi will be available in the US within two weeks for direct delivery to patients’ homes through Accredo Health Group, an Express Scripts specialty pharmacy.

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Coronavirus pharma news roundup – 07/08/20

Pharma’s reputation has soared due to the COVID-19 pandemic – but coronavirus is starting to bite companies’ sales. Find out more in our roundup of the biggest R&D, market access and digital stories from the past week.

  • The perception of pharma and medical companies has surged upward since the start of the COVID-19 pandemic, but they still lie mostly outside the top-rated firms in the FutureBrand Index. Roche, AstraZeneca, Novo Nordisk, and Sanofi all shot up the rankings in the first edition of the report since the start of the coronavirus crisis, but the big loser was Gilead Sciences, falling 71 places to 74 in the list.
  • The US government has selected a potential vaccine from Sanofi and GlaxoSmithKline for its Operation Warp Speed COVID-19 vaccine development initiative, committing up to $2.1 billion for an initial 100 million doses.
  • Novavax’s COVID-19 vaccine produced higher levels of neutralising antibodies than produced by recovered patients in an early trial, paving the way for a phase 3 trial and potential approval by year-end.
  • While the world waits for an effective coronavirus vaccine, Eli Lilly has started late-stage human testing of an antibody drug as an alternative way to prevent viral transmission in high-risk locations. The US drugmaker is testing the antibody – called LY-CoV555 and developed in collaboration with Canadian biotech AbCellera – in a phase 3 trial to see if it can prevent the spread of the coronavirus among residents and staff in US nursing homes.
  • Gillead lost $3.3bn in Q2, with the company blaming COVID-19 and its acquisition of immune-oncology company Forty Seven for the fall. It said COVID-19 has worsened the fall in hepatitis C sales because fewer patients have been visiting clinics and hospitals for visits and screenings.
  • Meanwhile, Bayer’s Q2 sales were down 2.5% to just over €10 billion, with pharma falling 8.8% to just under €4 billion, “weighed down” by COVID-19 and China’s new volume-based procurement policy for healthcare products.
  • The current level of test and trace in the UK is inadequate to prevent a sharp increase in coronavirus infections when schools reopen in September and there is further relaxation of social distancing rules, according to scientists.

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DBV craters on FDA’s peanut allergy immunotherapy rejection

DBV Technologies’ long and tortuous path to an FDA verdict on its Viaskin Peanut allergy shot has led to another dead end.

The France-headquartered biotech confirmed the complete response letter (CRL) from the US regulator today, adding another delay to a programme that is already falling well behind a rival therapy developed by Aimmune – Palforzia – which was approved in February.

The agency is asking for a new “human factor study” to examine how well the patch-based product adhere to the skin, and how that affects efficacy, according to DBV. Shares in the company lost more than a third of their value on the announcement.

The biotech initially filed for approval of Viaskin Peanut at the end of 2018, only to withdraw the application a few months later after an FDA request for more information on manufacturing.

It refiled last August, but by March of this year it was clear the application was in trouble over the adhesion issue.

DBV says it plans to request a meeting with the FDA to discuss its comments in the CRL as well, as that may be needed in another clinical trial to support another refiling.

“We are very disappointed in the FDA’s response, but continue to believe in the potential of Viaskin Peanut,” said DBV’s CEO Daniel Tassé.

The rationale behind Viaskin Peanut is to expose people with peanut allergy to small, rising amounts of peanut protein – which acts as an allergen – to encourage the immune system to develop tolerance over time.

While DBV’s product is delivered as a patch on the skin, Palforzia – which was the first drug to treat peanut allergy in the US – is administered as an oral dose and can be given to children aged four to 17. DBV has been seeking approval of its drug for the four to 11 age bracket.

Every month that Viaskin Peanut is kept from the market gives more time for Aimmune’s drug to get established of course, and likely reduces the return DBV could get on its investment.

Analysts have previously suggested that Palforzia could eventually become a $1 billion product, given there are around 1.8 million people with peanut allergy in the US, one million of them under the age of 18.

That said, the pandemic has cut hard into what should have been the strong early period for Aimmune’s first product, with the company reporting just $575,000 in revenue in the first half, and it remains to be seen if that is masking lacklustre take-up.

COVID-19 has also held up a phase 3 trial of Palforzia in younger children aged under four, according to California-based Aimmune.

The biotech is also expecting European approval for Palforzia before the end of the year, and a verdict in Switzerland in the middle of 2021.

Meanwhile, DBV has been restructuring its business to eke out its cash reserves, put at just under €226 million at the end of June.

The company  spent almost €80 million in the first half of the year however, and has announced significant job losses to make sure it can continue operating with cash on hand as long as possible. Analysts think it should last into 2022.

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How does HTA for orphan drugs differ across europe?

New research looks at the factors that speed up and slow down HTA appraisals for rare disease medicines across Europe.

Rare diseases drugs have always faced challenges when it comes to HTA approvals, even as governments bring in more regulatory policies that make their path through assessment easier.

Several factors make it difficult for HTA bodies often to assess orphan drugs, including a lack of robust trial data due to difficulties in finding patients, the absence of randomised controlled trials, the use of surrogate endpoints, and the lack of active drug comparators.

A new analysis from consulting firm CRA has honed in on the different challenges faced in four EU markets – England, France, Germany and Scotland – and looked at how manufacturers can increase the chances of a successful appraisal.

The research analysed more than 70 EMA-approved rare disease therapies and compared reimbursement recommendations from the regulatory bodies in each country, to see how HTA decisions potentially prolonged time to reimbursement.

The results show that HTAs for orphan drugs can vary widely across Europe, causing inconsistencies in evidence requirements and recommendations.

Rates of approval

The study reviewed all 80 European Medicines Agency (EMA) authorised drugs receiving an orphan designation between 1 January 2013 and 31 December 2019, analysing their HTA outcomes and time to reimbursement across France, Germany, England and Scotland.

A comparative analysis was then conducted on the 71 approved drugs that achieved a negotiated price in at least one of the four markets.

Germany had the highest approval rate of orphan drugs at 98% – however most of these recommendations (73%) were awarded a ‘non-quantifiable benefit’ rating, the automatic rating for an orphan drug, which shows the regulator did not see any benefit compared to comparator products (see graph 1). The authors also note that orphan drug trials with higher p values and surrogate endpoints are often accepted for assessment in the country.

A more favourable outcome from the German regulator took on average 1.4 times longer to achieve a final negotiated price (708 versus 510 days).

graph 1

Graph 1: Assessment of the HTA outcome in France, Germany, England and Scotland of all orphan drugs that obtained an EMA approval between 2013-2019. N above each bar equals the number of drugs reviewed by the respective HTA body. Source: CRA Analysis

France and England had comparable approval rates (92% and 91%, respectively); however, France reviewed almost twice the number of orphan drugs over the period of analysis (67 versus 35). Only 19% of the orphan drugs in France were awarded an Amelioration du Service Médical Rendu (ASMR) rating of V, which indicates no improvement in medical benefit. Drugs with an ASMR IV-V rating were reimbursed in 427 days, compared to 585 days for products with ASMR I-III (see Graph 2).

Graph 2

Graph 2: Comparison of the time to reimbursement (days) for EMA orphan drugs approved from 2013- 2019. Orphan drugs were reimbursed in at least one of the selected markets (N = 70). N within each bar equals the number of drugs with each outcome reviewed by the respective HTA body. Source: CRA Analysis

In England, two key mechanisms were often used to achieve approval: label restrictions or a patient access scheme (PAS).

Over one third (37%) of orphan drugs appraised by NICE only achieved approval in a positioning or population that was restricted versus the full regulatory approved label. Companies that accepted such restrictions saw faster approval time compared to no drugs with restrictions (407 versus 505 days).

Meanwhile, although introducing a PAS improved the chance of approval, the analysis suggests that it actually delays the overall appraisal time (523 versus 311 days).

Scotland had the highest rate of non-approval for orphan drugs. Thirty-three percent of drugs reviewed were not accepted, despite specific modifiers in place for rare disease products, including the incorporation of the patient voice through the country’s Patient and Clinician Engagement (PACE) meetings – which were included in 74% of orphan drug submissions between 2013-2019.

Improving HTA outcomes

The authors conclude that while the various concessions and modifiers introduced by different governments have a positive impact on minimising rejections and accelerating approval times, there are still challenges in capturing the full value of orphan drugs within the HTA process.

“Achieving more favourable outcome ratings, avoiding restrictions, or addressing uncertainty with a PAS all lead to prolonged appraisal times,” the  authors say. “Manufacturers are therefore still required to consider carefully their HTA launch strategy and complement this with additional evidence generation and engagement from a wider stakeholder group.”

The authors outline several approaches companies can take to improve the chances of success in orphan drug approvals and overcome the challenge of having limited data and evidence available.

One approach is to agree methods for ongoing real world data collection post-launch with HTA bodies.

They add that “creative” solutions to real world evidence collection could help, such as developing apps for patients and HCPs.

Meanwhile, it is also important to strive for wider engagement with the rare disease community and other stakeholders.

Listening to views from patients and HCPs can help with processes like Scotland’s PACE meetings – but more indirect forms of stakeholder engagement may also improve HTA outcomes, as the value-added services provided to these stakeholders can be leveraged during negotiations.

“For example, Galafold, an enzyme replacement therapy for Fabry’s disease, is primarily differentiated from existing treatments by providing a reduction in administrative burden,” the authors say. “Despite this, Galafold was able to achieve an ASMR IV in France, recommendation by NICE, and was accepted for restricted use in Scotland.”

They note that the perception of Galafold’s value may have been improved by the additional value-added services the manufacturer, Amicus Therapeutics, offered to a wider stakeholder group

For example, Amicus reimbursed amenability tests for patients with unknown mutations that could be referenced against Galafold’s amenability table via a physician support website. This service was accepted in the NICE evaluation as something which avoided additional resource implications for the NHS.

For more information contact the report’s authors:

Steven Kelly – [email protected]

Ioanna Stefani – [email protected]

Charlotte Poon – [email protected]

Nimisha RaJ – [email protected]

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Preparing for an influx of cell and gene therapy approvals

Cell and gene therapies offer some of the most groundbreaking advancements in patient care the pharma industry has ever seen. However, to fully realise the potential of these innovative therapies, integration across the supply chain is critical – particularly with reimbursement and logistics.

As of the end of 2019, there were 17 cell and gene therapy products approved by the FDA. Now, there is more momentum than ever to bring these innovative medicines to market, and the FDA anticipates that it will approve 10 to 20 cell and gene therapy products a year within the next five years.

These therapies can offer new opportunities to patients with conditions where there are few treatment options and no cures. But the potential these products offer could remain largely unrealised if manufacturers and their partners are not prepared. Cell and gene therapy innovators and other stakeholders across the supply chain need to set themselves up for the greatest chance of success by addressing three key challenges: access barriers; logistics; and the need for stakeholder education.

Addressing access barriers through innovative payment models

While cell and gene therapies offer novel treatment to patients who have limited options, the cost associated with each product – anywhere between $375,000 and $2 million – can create significant access barriers. This challenge is compounded compared to traditional treatments that typically require multiple doses, as many cell and gene therapies are one-time treatments.

This situation increases the risk for payers covering the cell and gene therapy, given that the long-term magnitude and durability of the product is not known at the time of first regulatory approval and patients switch insurance carriers throughout their lifetimes.

“Stakeholders across the industry have recognised the increasing need to consider alternatives to the standard payment system if cell and gene therapies are to become widely available”

Stakeholders across the industry, such as manufacturers and payers, have recognised the increasing need to consider alternatives to the standard payment system if cell and gene therapies are to become widely available. As a result, a variety of payment models have been discussed:

  • Value-based model: The payer pays only a portion of the full price upfront. If the therapy achieves prespecified outcomes, the payer remits the remainder in full. This model spreads the financial risk, therefore, between the payer and manufacturer, and has been the most commonly employed method to date.
  • Pay-over-time model: The payer agrees to a fixed price for the therapy but pays in regular installments, like with an annuity, spreading the cost over time.
  • Subscription-based model: This model offers the payer a flat rate for coverage of various cell and gene therapy products, which provides predictability and helps them offset the potentially high upfront costs of these therapies and realise longer-term cost-savings.

We have already begun to see payers and manufacturers of cell and gene therapies attempt to adopt alternative payment models for their products, and more should continue to do so as additional therapies come through the approval pipeline. With a range of interdependencies that affect the success of cell and gene therapies, manufacturers need to develop their reimbursement strategy early in the commercialisation process. It’s critical for manufacturers to consider various payment models for cell and gene therapies ahead of approvals so that they can maximise patient access for their products.

Ensuring therapies reach their patients

Manufacturers have noted that the delivery of critical shipments is one of the biggest challenges facing the advanced therapy industry, as if you cannot connect cell and gene therapies with patients their efficacy is irrelevant. The inclusion of patients into the cell and gene therapy supply chain, the potentially life-altering impact of the therapies and their high cost leaves no room for failure.

These therapies require timely delivery and maintaining precise temperature control is integral for the patient and the product. It calls for near-perfect execution ranging from mapping the best transportation route and planning for multiple contingencies (such as closed international borders), to how the packaging itself is evaluated, validated and used to maintain product integrity in all conditions.

Successful execution of these processes requires both manufacturers and other supply chain partners to maintain a robust logistics platform. Currently, many manufacturers are developing different logistics plans for each of the stages of a clinical trial, only to find out these processes don’t scale when it is time to commercialise. Developing a plan early that can scale will position a product for success as more therapies are reviewed and approved. Manufacturers need to work with their 3PL and distribution partners to ensure control and oversight throughout the product journey to the patient – failure to do so will put patient outcomes and commercial success at risk.

Promoting stakeholder education

Many stakeholders – spanning payers, providers and patients – do not understand the full clinical, logistical, operational, financial or reimbursement components associated with cell and gene therapies. Manufacturers can leverage the preliminary data they’ve gathered throughout their initial commercialisation journey to support education and awareness efforts with these key stakeholders.

As payers conduct product reviews earlier and earlier in the development lifecycle, their demand for pre-approval information continues to grow. However, recent research shows that a gap still exists between the evidence sought by healthcare decision makers and what is being shared by manufacturers. COVID-19 has also caused delays in providing information in a timely and relevant manner, causing even more challenges for stakeholders.

The use of Pre-approval Information Exchange (PIE) is one way to combat these challenges. PIE allows manufacturers to communicate ahead of approval to partners with accurate, and unbiased information on products or indications, and share information early that may result in a “place saved at the table” for their product. This information equips stakeholders with the education needed to understand a product’s value story and positioning. Partners embedded in the industry – particularly those with a patient-centric focus – can also offer manufacturers the information they need to showcase the value of these products to patients.

The cell and gene therapy space is continuing to evolve. Through analysing payment models, working with partners to navigate logistical challenges and leveraging data, patients will have more opportunities than ever to access the next generation of medicines. Overall, the collaboration between stakeholders across the supply chain will facilitate a world in which we see 10 to 20 cell and gene therapies not only approved each year but out in the market directly impacting patients.

About the authors

Alex Guite is vice president services and alliances at World Courier. As strategy and services lead, Alex is responsible for developing and executing key strategic initiatives.Before joining World Courier in 2013 as head of pricing, Alex spent nearly 3 years with Oliver Wyman as a consultant in the Health and Life Sciences practice.

Ana Stojanovska is vice president, reimbursement & policy insights at Xcenda. She has extensive practical knowledge in working with key stakeholders to motivate local coverage of new products by both public and private payers and providing strategic compendia analyses and ongoing coding support. Prior to Xcenda, Ana worked for a bipartisan, non-profit health policy organization in Washington DC, where she helped lead research, health policy analysis, media outreach, and fundraising.

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NICE backs kidney cancer combination from Merck KGaA and Pfizer

NICE has said a combination of Merck KGaA’s Bavencio and Pfizer’s Inlyta should be available as a first line option for kidney cancer patients for NHS patients in England.

The cost-effectiveness body okayed interim reimbursement from the Cancer Drugs Fund (CDF) in final guidance for adults with advanced renal cell carcinoma.

NICE said that the therapy could be made available to around 1,600 patients per year in England.

The cost-effectiveness body noted clinical trial data showing that the combination of Bavencio (avelumab) and Inlyta (axitinib) improved progression-free survival for an average of five months compared with Pfizer’s Sutent (sunitinib).

Sutent was first recommended in this indication by NICE as long ago as 2009.

NICE said that final trial results including overall survival data are not yet available, but said the drug has the potential to be cost-effective.

The combination therapy will be available via the CDF on an interim basis at a confidential discounted price.

Bavencio is administered by a drip every two weeks and Inlyta is taken as a pill twice a day.

There are other NICE-recommended alternatives in first-line kidney cancer such as Novartis’ Votrient (pazopanib) and Bristol-Myers Squibb’s immunotherapy combination of Opdivo (nivolumab) and Yervoy (ipilimumab) is also available.

Meindert Boysen, deputy chief executive and director of the centre for health technology evaluation at NICE, said: “The committee heard from patient representatives that having more first line treatment options for advanced renal cell carcinoma would be welcomed, as it would allow for more individualised treatment plans to better control the disease.

“We’re therefore pleased that, because of the joint working between the two companies, NHS England and NHS Improvement and NICE, eligible patients with advanced renal cell carcinoma will be able to access this combination therapy from today on the CDF, while more clinical data is collected.”

However the news was not so good for Kyowa Kirin – NICE rejected the Japanese pharma’s Poteligeo (mogamulizumab) in first draft guidance for mycosis fungoides, a type of non-Hodgkin’s lymphoma affecting the skin causing red patches or plaques that progress to skin tumours.

It also rejected Poteligeo for the closely related Sezary syndrome, which is caused by cancerous T-cells in the blood and lymph nodes.

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Coronavirus pharma news roundup – 31/07/20

Vaccines, AI-driven drug discovery and llamas all hit the headlines this week as the search for a way to end the COVID-19 pandemic continues. Here we highlight the biggest R&D, market access and digital coronavirus news of the past week.

  • Roche’s anti-inflammatory drug Actemra has failed in a phase 3 clinical trial that was testing to see if it improved the condition of patients with COVID-19 associated pneumonia.
  • The UK government has signed its fourth coronavirus vaccine deal, snapping up 60 million doses of an experimental shot being developed by Sanofi and GlaxoSmithKline.
  • A US government agency is to give a further $472 million to biotech Moderna, after it announced plans to expand a phase 3 trial for its potential COVID-19 jab.
  • The UK is providing funding to bring a software tool used to monitor patients during surgery to market “as soon as possible”, says its developer. Directed Systems has been awarded the COVID-19 Continuity Grant by Innovate UK to allow it to continue development of Hypotension Decision Assist (HDA), which is designed to help anaesthetists keep patients undergoing surgery safe.
  • US biotech AI Therapeutics has begun a phase 2 trial of its LAM-002A, an antiviral drug that has shown promise against the SARS-CoV-2 coronavirus in the lab. The company develops drugs that have been identified with a proprietary artificial intelligence (AI) algorithm that matches drugs to new indications.
  • Belgium’s ExeVir Bio is to accelerate development of a new treatment for COVID-19 based on llama antibodies, after a 23 million euro ($27 million) financing round.
  • AstraZeneca has beaten analysts’ expectations in its second quarter results, outshining its UK counterpart GlaxoSmithKline, which has been hit by disruption caused by the pandemic.
  • UK manufacturing exports fell sharply during the second quarter as the COVID-19 pandemic gathered pace, but pharma and healthcare products were much less affected, says a Lloyds Bank report.

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Roche’s Tecentriq claims melanoma OK, but don’t expect a sales surge

Roche’s checkpoint inhibitor Tecentriq has been cleared for another new use in the US – in melanoma – but could struggle to displace rival drugs from Bristol-Myers Squibb and Merck & Co.

The FDA has approved the PD-L1 inhibitor as a combination with two targeted drugs – MEK inhibitor Cotellic (cobimetinib) and BRAF inhibitor Zelboraf (vemurafenib) – as a first-line treatment for patients with advanced melanoma with BRAF V600 mutations.

The approval stems from the IMspire150 trial, which showed that the triplet therapy reduced the risk of disease progression or death compared to Cotellic, Zelboraf and placebo.

The median progression-free survival (PFS) was 15.1 months in the Tecentriq (atezolizumab) group compared with 10.6 months, although objective response rates in the two groups were similar at 66% and 65%, respectively.

That’s a solid result, and a compelling comparison to make when IMspire150 was started three years ago. Unfortunately for Roche, melanoma treatment has evolved in the interim and the standard of care for these patients has moved on.

BMS’ Opdivo (nivolumab) and Merck’s Keytruda (pembrolizumab) have been approved for use in melanoma since 2014, and right now the combination of Opdivo with BMS’ CTLA4-targeting checkpoint inhibitor Yervoy (ipilimumab) looks set to become the go-to therapy in the US.

Opdivo/Yervoy was cleared for BRAF V600-positive melanoma in 2015, and for all-comer melanoma patients the following year, giving oncologists years of experience with its use and – crucially – plenty of impressive follow-up data.

Last year, BMS reported updated results from the CheckMate-067 study showing that 52% of patients on the regimen were still alive five years later, with the benefit present even in patients who stopped taking the drugs early due to side effects.

Over the same period, Cotellic sales have shrunk from around $400 million to a little over $50m last year as immunotherapy displaced targeted therapy in this type of melanoma.

That said, there are tolerability issues with Opdivo/Yervoy that could encourage some doctors to consider the Tecentriq triple for their BRAF V600-positive patients. Overall however, melanoma is considered to be a nice addition to Tecentriq’s approved indications that won’t be a big driver for new sales.

That’s more likely to come from other new indications for Roche’s drug, including new approvals as a monotherapy and in combination with chemotherapy in previously-untreated non-small cell lung cancer (NSCLC) and as a combination with Roche’s Avastin (bevacizumab) in liver cancer.