AZ COVID jab efficacy debate is hindering EU’s vaccine drive

The spat between the EU and AstraZeneca over access to the company’s COVID-19 shot led to scathing remarks about its efficacy that now threaten to undermine the EU’s vaccination targets. 

The European Commission approved AZ’s AZD1222 vaccine for use in the EU in all adults aged over 18 at the end of January, more than a month after it was given a green light in the UK, but it seems people in some EU countries are reluctant to receive it and even deliberately missing appointments.

Several countries – including Germany – have approved AZD1222 only for use in people under 65, for example, while France‘s President  Emmanuel Macron memorably described it as “quasi ineffective” for people over that age threshold.

Now, there are reports of AZ’s vaccine languishing on the shelves in Germany as the public misses appointments in the hope of holding out for one of the other vaccines approved in the EU – from Pfizer/BioNTech and Moderna – that are viewed as being much more protective.

It’s a major turnaround from a few weeks ago when the EU was clamouring for access to the shot as its vaccination programme fell behind Israel, the UK, the US and other countries around the world – something that critics have blamed on the European Commission’s centralised procurement process.

Only 150,000 out of 1.5 million doses of AZD1222 delivered to Germany had been used ahead of the weekend, according to local media reports, which have also suggested AZ’s shot may be more likely to cause side effects.

DW.com said that while Germany’s government has said that everyone in the country who wants a jab will be offered one by September, this could be set back by up to two months unless millions of people are prepared to get AZD1222.

The news service added that just three to five people were turning up per hour at a vaccination site in Berlin’s disused Tegel airport, where only the AZ shot is available. Initially, Berlin was the only state in Germany to allow people to choose their vaccine, but that right has now been revoked and the pubic have to accept whichever jab they are offered.

An official spokesman for the German government attempted to restore confidence today, tweeting that AZD1222 is “highly effective…prevents many infections and protects against serious illness”.

New UK data released today has shown that four weeks after a dose of either the AZ or the Pfizer/BioNTech vaccines reduces the chances of hospitalisation by 81%.

At last count, Germany had provided at least a first dose to around 6% of its population – roughly in line with the rest of the EU27 – while the UK has achieved that milestone in 26%, more than 17 million people.

A Bloomberg report citing health ministry figures last week said that 85% of available Pfizer/BioNTech doses had been administered, along with around 29% of the Moderna vaccine, but that AZ usage was down at 9%.

It also reported that in France, the website where appointments are booked had hundreds of available slots for the AZ shot for healthcare professionals, but very few for the two other vaccines.

Last week, the EU ordered additional supplies of the Pfizer/BioNTech and Moderna vaccines to boost supplies, taking the total for each to 500 million and 310 million, respectively, with delivered due before the end of the year.

AZ has agreed to supply 300 million doses by the end of June, but has said it will likely be 75 million short of that commitment because of production delays at plants in the Netherlands and Belgium.

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France and Germany threaten AstraZeneca over vaccine shortage

Warning of ‘legal commitment’ and concern that doses might have been diverted from the EU to the UK

France and Germany have threatened legal action against the Anglo-Swedish pharmaceutical company AstraZeneca in the row over a shortage of coronavirus vaccine in the EU.

Talks between the European commission and the vaccine supplier are continuing over the lack of supply, with Brussels raising concerns that doses may have been diverted from plants in Belgium and Germany to the UK.

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EU plans video summit after doubling supply of Pfizer Covid vaccine

Bloc agrees deal for a further 300m doses as hopes are raised for speedier rate of inoculations

EU leaders are to hold a pandemic video summit on 21 January after the bloc said it had reached a deal with Pfizer and BioNTech for 300m more doses of their Covid-19 vaccine, giving the EU nearly half the firms’ global output for 2021.

The move raised hopes for speedier inoculation across the continent as the European regulator, which this week approved the Moderna shot, said it would authorise six doses from each vial of the BioNTech/Pfizer vaccine, increasing available jabs by 20%.

The Pfizer/BioNTech Covid jab is an mRNA vaccine. Essentially, mRNA is a molecule used by living cells to turn the gene sequences in DNA into the proteins that are the building blocks of all their fundamental structures. A segment of DNA gets copied (“transcribed”) into a piece of mRNA, which in turn gets “read” by the cell’s tools for synthesising proteins.

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BioNTech criticises EU failure to order enough Covid vaccine

Firm races to fill potential gap left by bloc’s gamble on several vaccines being approved

BioNtech has criticised the EU’s failure to order more doses of its coronavirus vaccine, saying it is now racing with its US partner Pfizer to boost production amid fears of a European “gap” left by the lack of other approved vaccines.

The Pfizer/BioNTech vaccine was the first to be approved by the bloc late last month, after being accepted by the UK, Canada and the US. They and other countries have also since approved the Moderna or Oxford/AstraZeneca vaccine, leaving the EU trailing behind.

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Ministers would be wise to play for time before ordering Sizewell C | Nils Pratley

Dashing ahead with a nuclear power station that’s modelled on Hinkley Point C would be reckless

This is the government’s problem as it reopens talks on a proposed nuclear power station at Sizewell C in Suffolk: it is contemplating ordering a replica of Hinkley Point C before the Somerset original has produced a single megawatt of electricity.

That is not a small point. Developer EDF’s pre-Hinkley version of its European pressurised reactor at Flamanville in Normandy is about a decade behind schedule. What’s more, EDF wants UK taxpayers or bill-payers to bear more of the construction risks at Sizewell, a less-than-compelling offer when you remember that Flamanville is also €9bn (£8.2bn) over budget.

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French startup lands $8.7M to advance microbiome therapies

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Founded in 2014, MaaT Pharma is pushing two therapies through clinical trials that are designed improve survival for patients with blood cancers and other diseases. Despite high-profile hiccups, the field of microbiome therapy remains attractive to investors.

Policy makers should ‘set their sights higher’ on U.S. drug pricing regulations, researchers say

Money pile and medicine pills representing medical expenses

A review published in JAMA found that bills introduced into the House and Senate don’t go nearly as far as existing drug pricing regulations other countries. The researchers listed eight key lessons from six nations.

GSK and Sanofi to start human trials of potential Covid-19 vaccine

World’s largest vaccine makers to begin testing on people in US with eye on rollout in early 2021

GlaxoSmithKline and Sanofi are to start testing their protein-based Covid-19 vaccine on humans for the first time, following promising results in earlier studies.

GSK, the world’s largest vaccine maker, and the French drugmaker Sanofi joined forces in April to work on an effective treatment to halt the devastating pandemic.

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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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Sanofi, GSK nab $2.1B deal from federal government to provide Covid-19 vaccine

The companies will provide 100 million doses of their jointly developed vaccine. But with a Phase I/II study planned in September, it is behind in development compared with those of Moderna and Pfizer and BioNTech, which have already started late-stage clinical testing.