Sanofi’s immunotherapy Libtayo gets FDA not in first line lung cancer

Sanofi’s cancer immunotherapy Libtayo (cemiplimab) has a third US indication after the FDA approved it for certain untreated lung cancer patients.

The approval in first-line lung cancer, in non-small cell lung cancer patients whose tumours have high PD-L1 expression brings the drug into competition with Merck & Co’s Keytruda (pembrolizumab), which has become the go-to therapy in this disease.

To be eligible for Libtayo patients must either have metastatic or locally advanced tumors that are not candidates for surgical resection or definitive chemoradiation, and the tumours must not have EGFR, ALK or ROS1 mutations.

This third approval for Libtayo follows a Priority Review, which lasts up to six months instead of the standard 10, and is reserved for drugs that represent significant improvements in safety or efficacy in treating serious conditions.

Ahmet Sezer, professor in the Department of Medical Oncology at Başkent University in Adana, Turkey and a trial investigator.

Sezer said: “Libtayo has demonstrated an impressive level of efficacy in advanced NSCLC with at least 50% PD-L1 expression in its pivotal trial.

“As published in The Lancet, in a prespecified analysis in the subset of patients proven to have PD-L1 expression of at least 50%, Libtayo reduced the risk of death by 43% compared to chemotherapy.

“This was achieved with a greater than 70% crossover rate to Libtayo following disease progression on chemotherapy, as well as the largest population of patients with pretreated and clinically stable brain metastases among advanced NSCLC pivotal trials to date.”

The data supporting the Libtayo approval are based on an analysis of 710 patients who were randomized to receive treatment in a phase 3 trial.

Eligible patients were intended to have PD-L1 expression of 50% or higher. In this patient population, Libtayo reduced the risk of death by 32% compared to chemotherapy.

Median overall survival in the Libtayo arm was 18 months, compared with 14 months in the chemotherapy arm.

Median progression-free survival was 8 months in the Libtayo arm, compared with 6 months in the chemotherapy patients.

These figures were based on an analysis of a subset of the randomised population excluding 147 patients whose tumours could not be retested or were later found to have less than 50% PD-L1 expression.

Libtayo was first FDA-approved in late 2018 for advanced cutaneous squamous cell carcinoma, followed by advanced basal cell carcinoma last month.

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Nektar lifted by Merck alliance for bempeg, new trial funding

Nektar Therapeutics is waiting on multiple data readouts for its lead drug bempegaldesleukin paired with strategic partner Bristol-Myers Squibb’s checkpoint inhibitor Opdivo, but that hasn’t stopped it signing up to test the drug with rival Keytruda from Merck & Co. 

Merck will pair Keytruda (pembrolizumab) with bempegaldesleukin (NKTR-214) – known as bempeg for short – in a phase 2/3 trial involving patients with squamous cell carcinoma of the head and neck (SCCHN) that if positive could support regulatory filings.

In an unusual move, the partners have also defrayed the risks in the new programme as the trial will be backed financially by private equity firms Abingworth and Blackstone, via their SFJ Pharmaceuticals subsidiary, with up to $150 million.

Shares in Nektar rose around 11% on the back of the twin announcements, which came shortly after the company was sued in a Delaware court by shareholders who accuse it of selling $171 million-worth of stock at prices inflated by a fraudulent scheme to hype the results of bempeg trials.

Last year, a similar lawsuit against the biotech was dismissed by a federal judge in a San Francisco court.

Bempeg is a new formulation of an interleukin-2-based drug Proleukin (aldesleukin), sold by Clinigen, that extends its action in the body and according to its developer overcomes a safety issue that has pegged back sales of the original drug.

The new trial – first-line treatment of SCCHN – is for an indication not currently covered by Nektar’s alliance with BMS. That was signed for $1.8 billion upfront in 2018 and extended a year ago, and is focusing on five indications across melanoma, bladder cancer, and kidney cancer for the Opdivo (nivolumab) and bempeg combination.

Under the terms of the original deal, Nektar retained the ability to develop NKTR-214 with other anti-cancer agents. In fact, a Keytruda/bempeg combination study in in non-small cell lung cancer (NSCLC) is due to read out later this year, and could lead to the first regulatory filing for the drug if positive.

BMS and Nektar meanwhile have a potential registration study in first0line melanoma on the way that could generate results later in 2021 or early 2022.

The deal with SFJ Pharma involves Nektar making annual milestone payments back to SFJ over the next seven or eight years – but only if bempeg secure regulatory approvals for “specified indications” including SCCHN.

The trial will enrol around 500 patients with metastatic or recurrent SCCHN with PD-L1 expressing tumours, and will compared Keytruda plus bempeg to Keytruda alone. An initial phase 2 cohort of 200 patients will be recruited to see if the combination can achieve a higher overall response rate.

If that goes to plan, phase 3 stage will kick in, looking at ORR, overall survival and progression-free survival, and the results from that are due in around 2024.

The deals with Merck and SFJ are an endorsement of the bempeg programme after initial results from mid-stage studies with the drug generated some lacklustre results in melanoma and triple negative breast cancer (TNBC).

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Guinea declares Ebola epidemic following first deaths since 2016

Guinea has officially declared it is dealing with an Ebola epidemic, after at least three people died from the virus.

The BBC reported that these first deaths from Ebola since 2016 were linked to the burial of a nurse, where four others fell ill with diarrhoea, vomiting and bleeding.

Newly developed vaccines will be supplied by the World Health Organization in a bid to contain the pandemic, officials said.

Between 2013 and 2016 more than 11,000 people died in the West Africa Ebola epidemic that begun in Guinea.

That outbreak mainly affected Guinea and its neighbours Liberia and Sierra Leone and several vaccines have since been trialled and successfully used to fight the disease in the Democratic Republic of Congo.

Drugs are also available that can increase the survival rate of patients.

Last month, four health and humanitarian organisations including the WHO announced they had established a global stockpile of Ebola vaccines.

The injectable single-dose Ebola vaccine is manufactured by MSD, known as Merck & Co in the US and Canada.

The European Medicines Agency licensed the Ebola vaccine in November 2019, and the vaccine is now prequalified by WHO, and licensed by the US Food and Drug Administration, as well as in eight African countries.

The WHO has joined with UNICEF, the International Federation of Red Cross and Red Crescent Societies (IFRC), and Médecins Sans Frontières (MSF), with financial support from Gavi, the Vaccine Alliance

An initial 6890 doses are now available for outbreak response with further quantities to be delivered into the stockpile this month and throughout 2021 and beyond.

Depending on the rate of vaccine deployment, it could take two to three years to reach the recommended level of 500,000 doses for the emergency stockpile of Ebola vaccines recommended by the WHO’s experts.

WHO, UNICEF, Gavi and vaccine manufacturers are continuously assessing options to increase vaccine supply should global demand increase.

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Merck gets a leg-up for Keytruda in first-line kidney cancer

New phase 3 data have shored up the position of Merck & Co’s cancer immunotherapy Keytruda in the increasingly competitive first-line kidney cancer market. 

The data from the KEYNOTE-581/CLEAR study reveal that the combination of PD-1 inhibitor Keytruda (pembrolizumab) with Eisai’s targeted tyrosine kinase inhibitor Lenvima (lenvatinib) reduced the risk of disease progression of death by 61% compared to Pfizer’s Sutent (sunitinib) in previously-untreated patients with renal cell carcinoma (RCC) – the most common form of kidney disease.

Merck and Eisai have already filed for approval of the combination on the strength of earlier results from the trial, but the presentation at the ASCO Genitourinary Cancers Symposium over the weekend was the time the data was put in front of oncologists.

The results were also published simultaneously in the New England Journal of Medicine, and showed that median progression-free survival was nearly two years with the combination, compared to nine months for Sutent, a standard therapy for RCC, and also cut the risk of death by a third.

Sutent has been superseded as the front-line standard in the last few years, as cancer immunotherapy combinations have come to the fore.

Keytruda is already approved alongside Pfizer’s TKI Inlyta (axitinib) in that setting – as is rival drug Bavencio from Germany’s Merck KGaA.

Meanwhile, Bristol-Myers Squibb’s double checkpoint inhibitor combination of Opdivo (nivolumab) and Yervoy (ipilimumab) is also well established in the first-line market, and BMS has also just picked up approval for Opdivo with Exelixis’ Cabometyx (cabozantinib), another TKI.

At the moment, Opdivo/Yervoy is generally used only for patients with intermediate or poor risk RCC, while the PD-1/TKI pairings are for all patients including those with favourable risk profiles, according to an editorial accompanying the NEJM paper by Alain Ravaud of the University Hospital Centre Bordeaux in France.

The editorial suggests the new study and earlier trials of PD-1/TKI combinations make these the standard first-line treatment, unless there are contra-indications, although he says there is clearly still a role for Opdivo/Yervoy.

Aside from oncologists experience with the regimen, which has now been approved for more than three years, so far as it is the only regimen so far with long-term survival data (48 months-plus) in patients with a poorer prognosis.

Approval of the Keytruda-Lenvima regimen would be a win-win for Merck, as it own a stake in Lenvima thanks to a $5.8 billion alliance agreed with Eisai in 2018.

Under that agreement Eisai and Merck are developing and marketing Lenvima jointly, both as monotherapy and in combination with Keytruda, with Eisai booking sales and the two companies sharing profits.

Merck and Eisai are expected to promote their combination heavily if its gets approved, so the main loser in the market seems to be Pfizer, which stands to lose market share for both Sutent and Inlyta in RCC.

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NICE backs NHS funding for MSD’s Keytruda combination in lung cancer

NICE has backed regular NHS funding England and Wales for Merck, Sharp and Dohme’s Keytruda in combination with pemetrexed and platinum chemotherapy in certain lung cancer patients.

In draft guidance NICE said the Keytruda (pembrolizumab) and chemo combination can now be reimbursed by the NHS in adults with untreated non-squamous non-small cell lung cancer (NSCLC) whose tumours have no epidermal growth factor (EGFR) or anaplastic lymphoma kinase (ALK) mutations.

The combination treatment was previously available to people through the Cancer Drugs Fund and has now been approved for routine commissioning on the NHS. Around 3,000 people will be eligible for this treatment in England.

Previously, standard care for tumours that have no EGFR-positive or ALK-positive mutations depended on PD-L1 status.

The new draft guidance, annouced after MSD provided further data on long-term survival, means people with advanced non-squamous NSCLC will now be eligible for Keytruda with pemetrexed and platinum chemotherapy for up to two years, regardless of their PD-L1 status.

NICE noted clinical trial evidence that suggests that patients live longer when treated with the Keytruda combination treatment compared with standard chemotherapy.

However, there was no change in overall survival in patients with a PD-L1 positive tumour with a score of 50% or more when compared to those treated with Keytruda monotherapy, which is standard care for this patient group.

Meindert Boysen, director of the NICE Centre for Health Technology Evaluation, said: “Through the Cancer Drugs Fund, pembrolizumab with pemetrexed and platinum chemotherapy has shown the potential to extend the lives of thousands of individuals, and we are pleased to now be able to recommend the treatment routinely.”

“With the new draft guidance, patients meeting the specifications will now be eligible to receive pembrolizumab with pemetrexed and platinum chemotherapy for two years, or until their disease progresses within this period.”

David Long, oncology business development director of MSD, known as Merck & Co in the US and Canada, said: “This is doubly significant at a time when we know, due to the impact of COVID-19 on patient presentation, the system is seeing an increase in the diagnosis of later stage cancers – especially in lung cancer. It is therefore all the more important that clinicians have the best choices available for their patients.”

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Aurinia’s Lupkynis for Lupus; FDA Fast Track Designation for Toripalimab; Wren Therapeutics’ Financing; Merck’s Covid-19 Vaccine Program End

Hot on the heels, Aurinia launches its drug in the Lupus market after GSK

Aurinia Pharmaceuticals has recently got the USFDA approval for its Lupkynis (voclosporin) in combination with a background immunosuppressive therapy regimen to treat adult patients with active Lupus nephritis (LN). Lupkynis is the first oral therapy to receive FDA nod for Lupus nephritis, a condition that causes inflammation of kidneys. It is one of the most common and serious complications of the autoimmune disease systemic lupus erythematosus (SLE). 

Lupus has been a challenging condition to treat for decades with only a limited number of therapeutic options. However, Aurinia is not the only player offering the cure. A month ago, GlaxoSmithKline earned the approval for its Benlysta, intravenous and subcutaneous option for Lupus, and became the first-ever therapy to get an approval for the indication. 

Although GSK has had an upper hand at the early launch of the drug, Aurinia has reported a significantly improved renal response rate of 40.8% versus 22.5% in the control arm while Benlysta’s difference with control was smaller (43% vs 32%). Furthermore, the company does not shy away from saying that its drug works rapidly and its oral RoA is another added benefit that makes it stand tall in the Lupus nephritis market. 

FDA Fast Track Designation to Toripalimab for Mucosal Melanoma

The USFDA granted Fast Track Designation to Junshi BiosciencesToripalimab for the first-line treatment of mucosal melanoma. Toripalimab is the first domestic anti-PD-1 monoclonal antibody to get commercial approval in China. 

The regulatory agency has also approved the Investigational New Drug (IND) application for a global Phase III trial of Toripalimab in combination with Axitinib versus Pembrolizumab for the first-line treatment of patients with advanced mucosal melanoma (Combination Clinical Trial). The trial investigated more than fifteen indications sponsored by over thirty pharmaceutical companies conducted globally, including in China and the United States. 

In 2018, Toripalimab had already obtained conditional approval from the National Medical Products Administration (the “NMPA”) for the second-line treatment of unresectable or metastatic melanoma. Further, it was included in the Guidelines of Chinese Society of Clinical Oncology (CSCO) for the Diagnosis and Treatment of Melanoma in 2019 and 2020 respectively. It also has received two supplemental New Drug Applications (NDAs) for the third-line treatment of recurrent/metastatic nasopharyngeal carcinoma and the second-line treatment of metastatic urothelial carcinoma were accepted by the NMPA in April and May 2020, respectively.

Wren Therapeutics Announces Financing of £12.4 Million 

Wren Therapeutics has announced the closing of a £12.4 million (c. $17.0 million) financing raising the total capital to approximately £33 million (c. $45 million). The financing was led by existing shareholder The Baupost Group, along with the participation from existing investors including LifeForce Capital and new investors including Schooner Capital and Industry Ventures.

The company plans to use the proceeds to accelerate two of its leading small-molecule programs towards the clinical development for the potential treatment of Alzheimer’s disease and various synucleinopathies including Parkinson’s disease

Merck Makes a Quick Exit in the COVID-19 Vaccine Development Fight 

The pharma goliath, Merck has decided to discontinue the development of its two experimental Covid-19 vaccines after the results from early trial gave some lacklustre results. Merck has taken a different approach from its rivals namely Pfizer, Moderna and Johnson & Johnson who were also in the domain developing vaccines against COVID-19

Merck had undertaken two programs, V590, which is based on the borrowed technology from Merck’s Ebola inoculation, whereas the second one, V591, is based on a measles vaccine used in Europe. However, both failed to cut the mustard this time and proved to be a blot in the company’s long history of successful vaccine development. 

Merck was a late-entrant in the development of the COVID-19 vaccine. The company had finished the recruitment of the first participants for early-stage safety studies at the time when its rivals were gearing up for presenting and demonstrating the efficacy of their candidates in late-stage trials. And the weak results took everyone by surprise. However, early or say quick fails are not as bad as the failure in the end-stage trials as they help the company to recover sooner from the grief and loss. 

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US Merck axes two COVID-19 vaccines, focuses on therapies instead

Merck & Co is to axe development of two COVID-19 vaccine candidates, focusing on development of two therapies instead following disappointing results in early trials.

US-based Merck & Co said the decision followed findings from phase 1 clinical studies of the vaccines codenamed V590 and V591.

The company – known as MSD outside North America – said that although the vaccines were well tolerated, the immune responses seen were weaker than natural immunity and those reported for other SARS-CoV-2 vaccines.

The World Health Organization’s regularly updated vaccine tracking webpage says there are 64 vaccines in clinical development, with several approved or close to the market.

With such tough competition, Merck made an easy call following the poor results and has decided to focus instead on advancing two therapies for COVID-19, MK-7110 and MK-4482 (molnupiravir).

The company is also continuing research into a measles-virus vector, which was added to its pipeline following its takeover of Themis last year.

It is also continuing to look at the vesicular stomatitis virus vector-based technology it developed in partnership with the not-for-profit International AIDS Vaccine Initiative (IAVI).

The company was more upbeat about the prospects for its two therapies, however.

MK-7110 (formerly CD24Fc) is a potentially first-in-class investigational recombinant fusion protein that modulates the inflammatory response to SARS-CoV-2, principally by targeting a novel immune pathway checkpoint.

Interim results from a phase 3 study showed a greater than 50% reduction in the risk of death or respiratory failure in patients hospitalized with moderate to severe COVID-19. Full results from this study are expected in the first quarter of 2021.

In December, Merck announced a supply agreement with the U.S. government to advance the manufacturing and initial distribution of MK-7110.

Molnupiravir is being developed in collaboration with Ridgeback Bio and is an oral novel investigational antiviral agent in phase 2/3 clinical trials in both hospital and outpatient settings.

The phase 2/3 study is expected to be completed by May and the first efficacy data could be published in the first quarter if Merck deems it to be “clinically meaningful”.

Merck and its collaborators plan to submit the results of the phase 1 studies for V590 and V591 for publication in a peer-reviewed journal.

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FDA approves Bayer/Merck & Co heart failure drug

Bayer and Merck & Co’s heart failure drug vericiguat has been approved by the FDA under the brand name Verquvo, in an increasingly competitive market.

Verquvo has been approved to reduce risk of cardiovascular death and heart failure hospitalisation in adults with symptomatic chronic heart failure and ejection fraction less than 45%.

The drug can be used after hospitalisation for heart failure or in patients in need of intravenous diuretics.

But the drug is entering an increasingly competitive market, where Novartis and AstraZeneca are vying for supremacy.

Entresto (sacubitril+valsartan) was FDA-approved in patients with reduced ejection fraction five years ago.

Meanwhile, AstraZeneca’s Farxiga (dapagliflozin), originally a diabetes drug, was approved in the US last year in heart failure with reduced ejection fraction.

The FDA is also quickly reviewing Boehringer Ingelheim’s Jardiance (empagliflozin) in heart failure, AZ’s big rival in the market for SGLT2 inhibitor class drugs.

Verquvo’s approval is the first for patients following a hospitalisation for heart failure or who need for outpatient IV diuretics and is based on the results of the pivotal phase 3 VICTORIA trial and follows a priority regulatory review.

VICTORIA’s main efficacy goal was to determine whether Verquvo is superior to placebo, both in combination with other heart failure therapies, in reducing the risk of cardiovascular death or heart failure hospitalisation in adults with symptomatic chronic heart failure and ejection fraction less than 45% following a worsening heart failure event.

Verquvo met the primary efficacy objective, with the study showing there was a 4.2% reduction in annualised absolute risk in the treatment group compared with placebo.

Therefore, 24 patients would need to be treated over an average of one year to prevent one death or heart failure hospitalisation.

VICTORIA is a large phase 3 trial involving 5,050 patients with heart failure with ejection fraction less than 45%.

Dr Paul W. Armstrong, cardiologist and Distinguished University Professor of Medicine at the Canadian VIGOUR Centre, University of Alberta, and study chair of the VICTORIA trial, said: “Patients with symptomatic chronic heart failure and reduced ejection fraction have a high risk for hospitalisation after experiencing symptoms of heart failure requiring outpatient IV diuretic treatment or hospitalisation.

“By some estimates, more than half of these patients are rehospitalised within a month of discharge due to a worsening event and approximately one in five die within two years.

“The approval of Verquvo provides doctors, health care professionals, and patients with a welcome new option to current available therapies.”

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Ex-Merck & Co scientist accused of stealing trade secrets could face jail

A former Merck & Co scientist could face up to 10 years in prison after he was accused of stealing trade secrets relating to drugs including the cancer immunotherapy Keytruda by US authorities.

In a document outlining the charges against Shafat Quadri, of North Potomac, Maryland the US Department of Justice (DoJ) referred only to “one of the largest pharmaceutical companies in the world” based in New Jersey.

But supporting information refers to data from cancer drug Keytruda (pembrolizumab) and Quadri’s Linkedin profile shows he worked at New Jersey-based Merck & Co around the time of the incidents before taking a role at AstraZeneca.

Quadri, formerly Merck’s head of medical and scientific affairs, immune oncology, has been charged with one count of theft of trade secrets and one count of unauthorised transmission of trade secrets, some relating to the multi-billion dollar cancer immunotherapy Keytruda (pembrolizumab).

According to the DoJ, the company contacted the FBI in October 2019 to report suspicious activity by Quadri, who had been employed there since 2015 as director of medical and scientific affairs, immune oncology.

The company said an internal investigation found Quadri had copied and removed thousands of files containing proprietary information before he left in September 2019,

This included research protocols, data and strategic plans, using unauthorised USB devices and personal email accounts to transfer the information that he had access to as part of his job.

Some documents were copied and removed and the trade secrets were also sent to an email address controlled by his “subsequent employer” and one of Merck’s competitors, according to the document.

Quadri was not authorised to keep the documents, the DoJ noted, and the investigation showed the company regularly monitors its employees’ use of company-provided technology and systems.

The count of theft of trade secrets charge carries a maximum potential penalty of up to 10 years in prison and a fine of up to $250,000, or twice the gross pecuniary gain or loss.

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High hopes as Inventiva takes NASH contender into phase 3

Analysts are continuing to back Inventiva’s lanifibranor as a potential “best-in-class” drug for the fatty liver disease NASH, as the company prepares for the launch of a phase 3 trial in spring.

A team of analysts from Jefferies led by Lucy Codrington noted the design of the trial, which will have a dual goal measuring both liver inflammation and scarring could give an edge over potential competitors.

There are no approved drugs for NASH – full name non-alcoholic steatohepatitis – after the FDA rejected Intercept’s obeticholic acid last year.

The regulator said it wanted more long-term safety and efficacy data from the REGENERATE study before making a final decision on the drug, which had been expected to be the first entrant into a likely multi-billion dollar market niche.

According to the latest analysis from Jefferies the design for the phase 3 NATIVE3 study from Inventiva has been okayed by regulators and the case for lanifribanor has already been boosted by “stellar” results in phase 2.

The decision to include two endpoints of inflammation and scarring is important because improvements in both these measures are likely to lead to an improved prognosis.

Lanifibranor is also taken orally, making it convenient for patients and Inventiva is hoping to offer a choice of two doses offering doctors the ability lower the strength of the medication to control side-effects such as oedema.

The trial will take a while however, with results not due until the second half of 2023, with sales forecast to peak at around $2.6 billion annually if approved.

The Jefferies team also noted that the French biotech is also partnered with AbbVie to develop an oral successor to its inflammatory diseases blockbuster Humira (adalimumab).

Proof-of-concept phase 1b data is due from the drug codenamed ABBV-157 is due this quarter, which will help AbbVie decide on whether to continue development.

A host of other pharma companies including Gilead, Novo Nordisk, Merck & Co are also developing potential NASH drugs.

Only this morning, Novo Nordisk selected the first candidate from a project with Dicerna to find new gene-silencing drugs to treat liver-related diseases including NASH.

 

 

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The top 5 pharma M&A deals of 2020

2020’s M&A activity hasn’t quite reached the heights of last year’s, where two pharma mega-mergers – BMS’ buyout of Celegne and AbbVie’s acquisition of Allergan – accounted for almost 40% of total M&A deal values.

That said, there were still some interesting moves indicating new directions of travel for big pharma players – with most deals focused on specific drugs from biotechs, particularly in cancer (though we did get rumours of an AstraZeneca-Gilead merger, which would have been the biggest pharma M&A deal of all time).

Here we take a look at the biggest mergers and acquisitions of 2020 and what they might mean for the companies involved.

AstraZeneca & Alexion

By far the biggest pharma deal of the year is AstraZeneca’s late-breaking offer to buy Alexion for $39 billion.

Alexion has routinely featured among lists of top biopharma takeover prospects in the last couple of years, and with the purchase, AZ will bolster its immunology franchise with $4 billion blockbuster Soliris (eculizumab) and longer acting follow-up Ultomiris (ravulizumab), plus a pipeline of 11 drugs for rare and autoimmune diseases.

It marks something of a departure from AZ’s relentless focus on deal-making in oncology, its top product category, and also comes as Alexion has been locked in a battle with activist shareholders pushing for a sale.

Boston, US-based Alexion spent a lot of 2019 arguing the merits of remaining independent, saying that while Soliris is approaching the end of its patent life – with heavyweight competitors like Amgen already eyeing the biosimilar market for the drug – Ultomiris and its pipeline could help drives sales to $9 to $10 billion in 2025.

The threat of biosimilar competition to its cash cow has weakened Alexion’s share price, providing an opportunity for AZ, which has been rumoured to be angling for a large acquisition for several months.

While the first biosimilars to Soliris have already reached the market in some countries like Russia, Alexion cut a settlement deal with Amgen in the summer that prevents the latter’s biosimilar version of Soliris from entering the US market until 2025, avoiding a near-term cash cliff.

In the meantime, Ultomiris has been gathering momentum, fuelled by intravenous dosing every eight weeks, rather than every two weeks with Soliris. It racked up $340 million in sales last year, and added another $763 million in the first nine months of this year, backing up its blockbuster credentials.

Meanwhile, AZ will also pick up three other drugs – Strensiq (asfotase alfa) for hypophosphatasia, Kanuma (sebelipase alfa) for lysosomal acid lipase deficiency (LAL-D) and anticoagulant reversal agent Andexxa (andexanet alfa) – that collectively brought in almost $675 million in the first nine months of 2020.

Gilead & Immunomedics

The AZ-Alexion deal is likely to be the only big pharma merger this year, but Gilead’s purchase of US biotech Immunomedics and its potential cancer blockbuster Trodelvy isn’t far off it in terms of value, with the deal totalling $21 billion.

California-based Gilead announced its strong intentions in oncology in 2017 with its $11.9 billion buy of Kite Pharma and followed that earlier this year by acquiring immuno-oncology firm Forty Seven for $4.9 billion (see below). Shoring up its assets in a wider range of disease areas will help the company weather the storm as the pool of patients eligible to receive its hepatitis C drugs such as Sovaldi shrinks.

Trodelvy (sacituzumab govitecan) is a first-in-class TROP2 antibody-drug conjugate drug that was granted accelerated approval by the FDA in April for adults with metastatic triple-negative breast cancer (TNBC), who have received at least two previous therapies for metastatic disease.

Data from trials of the drug wowed ESMO in September – Trodelvy was shown to significantly extend overall survival (OS) and improved overall response rate (ORR) and clinical benefit rate (CBR), compared with standard chemotherapy in TNBC patients with brain metastases treated with at least two therapies.

The 500-plus patients in ASCENT had received a median of four previous anticancer treatments, but Trodelvy significantly improved OS with a median of 12.1 months, compared with 6.7 months in patients treated with chemotherapy.

Johnson and Johnson & Momenta

This $6.5 billion deal means that J&J has added potential inflammatory disease blockbuster nipocalimab to the pipeline at its Janssen pharmaceuticals unit.

J&J thinks that Momenta’s lead drug nipocalimab could be a kind of Swiss army knife drug that could be used across a range of inflammatory diseases including maternal-foetal disorders, neuro-inflammatory disorders, rheumatology, and autoimmune haematology.

The success of AbbVie’s Humira (adalimumab), which peaked at almost $20 billion in sales in 2018, demonstrates the potential of inflammatory diseases drugs to make mega-bucks.

Johnson & Johnson’s own Remicade (infliximab) was also a blockbuster several times over thanks to approvals in a range of inflammatory diseases including Crohn’s, rheumatoid arthritis and psoriasis.

But like the rest of this first generation of antibody-based drugs, Remicade has been hit by cheaper competition from biosimilars and the hunt is on for newer drugs that outperform standard therapy in terms of safety and efficacy.

Whether nipocalimab achieves the astronomical figures seen from Humira and Remicade remains to be seen – but the price J&J has paid shows the big pharma thinks it has considerable potential.

Momenta is best known for producing a generic version of Teva’s multiple sclerosis drug Copaxone (glatiramer), but nipocalimab is the company’s lead pipeline asset and the main rationale behind the acquisition.

“The first wave had disproportionate health, economic and social impacts on people in lower socioeconomic groups and those with black, Asian and minority ethnic backgrounds”

Gilead & Forty Seven

Further cementing Gilead’s ambitions in cancer, this $4.9 billion deal adds an antibody targeting several blood cancers to the company’s research pipeline.

Forty Seven is based in Menlo Park, a short drive away from Gilead’s base in Foster City, and is developing magrolimab, which is targeting myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and diffuse large B-cell lymphoma (DLBCL).

A potential first-in-class therapy, magrolimab targets CD47, which produces a “do not eat me” signal that allows cancer cells to avoid destruction (an area AbbVie has almost invested significantly in).

By targeting CD47 it’s hoped that magrolimab will allow the patient’s own innate system to engulf and eradicate cancer cells.

The company presented promising results from a phase 1b study of magrolimab in patients with MDS and AML at the American Society of Hematology meeting in December.

Sanofi & Principia Biopharma

Sanofi added a potential multiple sclerosis drug to its pipeline when it bought Principia Biopharma for up to $3.68 billion in August.

The French pharma paid $100 per share in cash for San Francisco-based Principia, which specialises in Bruton’s kinase (BTK) inhibitor drugs, after the deal was unanimously agreed by both boards of directors.

Sanofi’s acquisition builds on a partnership to develop central nervous system drugs that began in late 2017.

In a statement Sanofi said that the acquisition will give it full control of the brain-penetrant BTK inhibitor SAR442168, making marketing more efficient and eliminating any royalty payments due under the 2017 agreement.

The drug known for short as ‘168 reduced multiple sclerosis brain lesions by 85% compared with placebo in a phase 2b trial.

Phase 3 development has begun and will comprise four pivotal trials across the MS disease spectrum.

Another of Principia’s BTK inhibitors, rilzabrutinib, is being tested in phase 3 for patients with moderate to severe pemphigus, a rare and debilitating autoimmune disease that causes blistering of the skin and mucous membranes.

Principia also has a topical BTK inhibitor, PRN473, which is in phase 1 development for immune diseases that could benefit from local application to the skin.

The deal follows Sanofi’s announcement late last year that it is rethinking its R&D operations, turning its back on diabetes and focusing on badly needed “transformative” therapies and maximising the potential of its asthma and eczema drug Dupixent.

CEO Paul Hudson, who was appointed to the role in June last year, has already acquired the oncology firm Synthorx and signed a potential $2 billion collaboration with Kymera Therapeutics to develop immune-inflammatory drugs.

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Merck cuts $1bn deal with Janux for cancer T-cell therapies

In a deal that could top $1 billion, Merck & Co has teamed up with US biotech Janux Therapeutics to bring T-cell immunotherapies to cancer patients.

The agreement sees San Diego-based Janux in line for around $500 million in milestones apiece for two T-cell engager therapies – which bind to a tumour cell and recruit a patient’s T cells to eradicate tumour cells – that will be developed using Janux’ TRACTr platform.

Each programme includes undisclosed upfront and milestone payments plus royalties on sales, with Merck indicating in a statement that it will be funding the research.

It’s the first major partnership for Janux, which was set up in 2017, and could be the last to be organised by Merck’s R&D head Roger Perlmutter who is retiring from the big pharma company at the end of the year.

Perlmutter has directed Merck to bolster its pipeline with a series of deals in the last few months of his tenure, as investors have started to ask whether the company has become a bit too reliant on checkpoint inhibitor Keytruda (pembrolizumab), which accounts for around a third of its sales.

Just a few weeks ago, Merck (known as MSD outside North America) paid $425 million to get hold of OncoImmune. The headline of the deal was an experimental COVID-19 drug, but it also claimed rights to a pipeline of early-stage oncology drugs.

Other recent deals include a $2.8 billion acquisition of VelosBio and its anti-ROR1 antibody-drug conjugate (ADC) VLS-101, as well as a partnership with Dragonfly Therapeutics for a cancer programme based on the biotech’s TriNKET natural killer (NK) cell engager platform.

Earlier in the year there was also $2.55 billion alliance with Taiho and Astex for cancer antibodies, including a KRAS drug, and a $4.2 billion deal with Seattle Genetics covering ADCs for  breast cancer and other solid tumours.

The deal-making activity signals Merck’s determination to stay at the forefront of cancer immunotherapy with new medicines that could complement Keytruda and broaden its portfolio.

Janux says its platform could allow it to succeed where other T-cell engager developers have failed due to “dose-limiting toxicities, poor pharmacokinetic profiles, and attenuated efficacy,”

In preclinical testing, its TRACTr drugs have been shown to offer the same anti-tumour activity as older T-cell engager drugs, but don’t cause the release of cytokines that can lead to a runaway immune response and damage to healthy tissues.

Those problems mean that so far only one T-cell engager has reached the market – Amgen’s Blincyto (blinatumomab) for leukaemia – although many others are coming through development.

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Merck & Co adds COVID-19 drug to pipeline with OncoImmune buy

Merck & Co is to buy US biotech OncoImmune for at least $425m, adding a potential new therapy for COVID-19 to its pipeline.

The pharma company, known as MSD outside North America, will pay the money up front with OncoImmune shareholders receiving further undisclosed milestone payments if certain sales and regulatory goals are achieved.

What attracted Merck & Co’s attention were interim findings of a phase 3 study showing OncoImmune’s CD24c – also known as Saccovid – significantly cut recovery time or progression to death or respiratory failure in patients with severe or critical disease compared with placebo.

Data was based on findings from 203 patients, around 75% of planned population of the trial, which the privately-owned US biotech said is fully recruited.

The pre-specified interim efficacy and safety analyses were performed when 146 patients achieved clinical recovery from COVID-19, a milestone achieved with 203 enrolments.

The trial was opened in April this year and activated in 15 medical centres in the US.

It involved patients requiring oxygen support, including those requiring supplemental oxygen, high flow oxygen, and non-invasive ventilation.

They were randomly assigned into two arms receiving either SOC plus a single dose of Saccovid or standard of care plus placebo.

Saccovid is a first-in-class recombinant fusion protein that targets the innate immune system, which had originally been developed for prevention of graft versus host disease (GVHD) following stem cell transplants in patients with leukaemia.

It has been studied in GVHD in phase 2 clinical trials, and a pivotal phase 3 clinical trial has already begun in GVHD.

In COVID-19 research, Merck & Co is already collaborating with Ridgeback Biotherapeutics to develop an oral antiviral drug, which is in phase 2/3 development.

Merck & Co is also conducting clinical trials to evaluate two COVID-19 vaccine candidates: V590, being developed through a collaboration with IAVI, which utilizes a recombinant vesicular stomatitis vector, and V591 which uses a measles virus as a vector.

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Merck & Co/Eisai eye kidney cancer use for immunotherapy combination

Merck & Co and Eisai are to file results from a phase 3 trial testing a combination of the former’s immunotherapy Keytruda, combined with the latter’s cancer drug Lenvima in untreated patients.

Keytruda (pembrolizumab) and Lenvima (lenvatinib) outperformed standard care – Pfizer’s Sutent (sunitinib) – in untreated patients with advanced renal cell carcinoma when measured against progression-free survival (PFS) and secondary goals of overall survival (OS) and overall response rate (ORR).

The companies said the results in the intention to treat population would be shared with regulators across the world.

Merck & Co, known as MSD outside North America, gave no further details about the results but said that the improvements were “statistically significant and clinically meaningful” in the group that included across all risk group categories – favourable, intermediate and poor.

Results came from the 1,050 patient KEYNOTE-581/CLEAR trial, also known as Study 307, testing Lenvima in combination with Keytruda or in combination with everolimus, with patients taking Pfizer’s Sutent in the control group.

Patients were randomly assigned to three groups, either receiving Lenvima (18mg orally once daily) in combination with everolimus (5mg orally daily), Lenvima (20mg orally once daily) plus Keytuda (200mg intravenously every three weeks), or Sutent daily once daily for four weeks on treatment followed by two weeks off treatment.

The primary endpoint is PFS by independent review per RECIST v1.1 criteria.

Further details will be revealed at an upcoming medical meeting.

Keytruda was approved in combination with Pfizer’s Inlyta (axitinib) in first line kidney cancer last year, which is competing against the combination of BMS’ rival PD-1 inhibitor Opdivo (nivolumab) and CTLA4 inhibitor Yervoy (ipilimumab).

Merck KGaA/Pfizer’s Bavencio (avelumab), was approved for first-line RCC in combination with Inlyta in May last year.

US-based Merck and Eisai are continuing to study the Keytruda plus Lenvima combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program across 19 trials in 13 different tumor types (endometrial carcinoma, hepatocellular carcinoma, melanoma, non-small cell lung cancer, RCC, squamous cell carcinoma of the head and neck, urothelial cancer, biliary tract cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer and triple-negative breast cancer).

 

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Merck & Co buys cancer biotech VelosBio for $2.75bn

Merck & Co has agreed to buy California biotech VelosBio and its experimental cancer drug for $2.75 billion in cash.

Known as MSD outside North America, the big pharma already has a firm foothold in cancer thanks to its immunotherapy Keytruda (pembrolizumab), which has been on the market for several years and has proven to be effective across a wide range of oncology indications.

But cancer is a highly competitive field and like rivals such as Bristol-Myers Squibb and Roche, Merck & Co is always looking for relatively small acquisitions that could bring in new technology and raise the bar in terms of safety and efficacy.

Based in San Diego, VelosBio is a privately held biotech specialising in a new class of drug that target receptor tyrosine kinase-like orphan receptor 1 (ROR1).

Its lead candidate in clinical development is VLS-101, an antibody-drug conjugate (ADC) targeting ROR1 that is being tested in a phase 1 and a phase 2 clinical trial for patients with blood cancer and solid tumours, respectively.

A phase 2 trial of VLS-101 in solid tumours began last month, including patients with hard to treat triple-negative breast cancer, hormone receptor-positive and/or HER2-positive breast cancer and non-small cell lung cancer (NSCLC).

VelosBio is also due to present detailed results from a phase 1 trial showing a complete response in seven out of a cohort 15 patients with mantle cell lymphoma and four out of five patients with diffuse large B-cell lymphoma.

Patients in that trial had been heavily pretreated and had failed to respond to other anticancer drugs.

The biotech also has a preclinical pipeline of next-generation ADCs and bispecific antibodies targeting ROR1, which could be used in tandem with VLS-101.

The transaction is expected to close at the end of 2020.

In separate announcements Merck said that Lynparza (olaparib), which it develops in partnership with AstraZeneca, had been approved in two new indications in Europe

The new label extensions cover BRCA1/2-mutated metastatic castration-resistant prostate cancer and first-line maintenance treatment for HRD-positive advanced ovarian cancer.

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Genprex cancer gene therapy paired with AZ, Merck lung cancer drugs

An experimental gene therapy developed by Texas biotech Genprex will be paired with AstraZeneca’s Tagrisso and Merck & Co’s Keytruda – both leading their respective drug classes in the treatment of non-small cell lung cancer (NSCLC).

The two phase 1/2 trials are zeroing in on NSCLC patients with specific molecular biomarkers, to see if adding Genprex’ Reqorsa (quaratusugene ozeplasmid) – which delivers a gene that suppresses tumour growth – can enhance the activity of the AZ and Merck drugs.

The first trial, called Acclaim-1, will pair EGFR inhibitor Tagrisso (osimertinib) with Reqorsa as a second-line treatment for EGFR-mutated NSCLC patients whose cancer has progressed after first-line Tagrisso treatment.

The Acclaim-2 trial meanwhile will add Reqorsa to PD-1 inhibitor Keytruda (pembrolizumab) in NSCLC patients with PD-L1 expression levels of 1% to 49%, according to the partners. Both studies are due to start in the first half of next year.

Tagrisso is the top-selling EGFR inhibitor, with sales of almost $3.2 billion last year, while Keytruda dominates the market for cancer immunotherapies for NSCLC, accounting for a large chunk of its $11 billion-plus 2019 sales tally.

If positive, the trials would allow Reqorsa to piggyback on that success – assuming it makes it to market. So far, Genprex only has data for the therapy from two phase 1 trials, and part of a phase 2 study showing preliminary evidence of safety as well as efficacy in NSCLC.

Genprex’ therapy takes the form of a copy of the TUSC2 gene in a non-viral lipid nanoparticle formulation, delivered via an intravenous infusion, and was originally developed at the University of Texas’ MD Anderson Cancer Centre in the US.

After infusion, the nanoparticles are taken up by tumour cells, says Genprex, and leads to the expression of the TUSC2 gene into a protein that reprograms them to die.

In preclinical studies, the gene therapy also seems to block mechanisms involved in drug resistance, including TIM3, a bypass pathway that can lead to failure of PD-1-based therapy.

The FDA awarded fast-track status to the Tagrisso/Reqorsa for the treatment of EHGFR-mutated NSCLC earlier this year, as nearly all patients receiving AZ’s drug eventually experience disease progression.

According the company’s data, the median time to progression after first-line Tagrisso is about 18 months.

Austin-based Genprex has been preparing for the Reqorsa clinical trials programme, over the last few months, ramping up its manufacturing capacity for the gene therapy via an agreement with contract manufacturing organisation (CMO) Aldevron.

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Drugs and vaccines may not swiftly end pandemic, says Merck & Co’s CEO

Merck & Co’s CEO Kenneth Frazier has warned that the drugs and vaccines in the pipeline to combat COVID-19 may not be enough to swiftly end the pandemic.

Speaking to CNBC, Frazier said that the drugs and vaccines to treat COVID-19 are not a “silver bullet” solution to the pandemic, meaning people are likely to be wearing masks and practicing social distancing measures well into 2021

He told CNBC’s Squawk Box: “I don’t see the therapeutics that we have – or the vaccines that are coming – as a silver bullet.

“I would say certainly well into 2021 we’ll still be trying to observe these public health measures.”

Frazier said he is “very optimistic that in the near future” there will be positive results coming from late-stage clinical trials for COVID-19 vaccines and therapeutics.

A potential vaccine is unlikely to be widely available for people until mid-2021, Frazier noted.

It’s expected that vaccines will only work in around 70% of cases and Dr Anthony Fauci, White House coronavirus adviser, said that the likelihood of a highly effective COVID-19 vaccine providing coverage in around 98% of people is slim.

Frazier added: “The natural history of viruses is that they don’t go away.

“I don’t think we should tell people that they can expect to give up on those public health measures anytime soon.”

US-based Merck & Co is developing two separate potential COVID-19 vaccines, one from the Australian vaccine manufacture Themis that it acquired in July and with scientific non-profit organisation IAVI.

However the company known as MSD outside North America is well behind the leaders in the COVID-19 vaccine race, which according to the World Health Organization are phase 3 candidates from China’s Sinovac and Sinopharm, followed by the UK’s AstraZeneca.

Frazier made his comments as the US sees a deadly surge of the coronavirus just as voters go to the polls to decide whether incumbent Republican president Donald Trump stays on for another four years, or is replaced by his Democrat rival Joe Biden.

Trump’s handling of the pandemic has been a focus point in the campaigns for the White House, with nearly 9.4 million confirmed cases and 231,000 deaths attributed to the disease.

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FDA sets Feb decision date for Libtayo lung cancer challenge to Keytruda

The FDA has started a priority review of Regeneron and Sanofi’s checkpoint inhibitor Libtayo in first-line non-small cell lung cancer (NSCLC), based on data they hope will carve out a niche for the drug in a highly-contested market.

PD-1 inhibitor Libtayo (cemiplimab) impressed oncologists earlier this year with results from a trial in previously-untreated NSCLC patients whose tumours had high levels of the PD-L1 biomarker, showing the drug reduced the risk of death by 32% compared to platinum chemotherapy.

Updated results from the study reported at the ESMO congress in September showed that among patients with confirmed PD-L1 expression of 50% or more – the patient group targeted in Sanofi and Regeneron’s marketing application – the mortality rate was reduced by 43%.

If the FDA cleared Libtayo by its deadline of 28 February, the drug will join the clutch of checkpoint inhibitors vying for a slice of the first-line NLSCLC market, nipping at the heels of Merck & Co/MSD’s mega-blockbuster Keytruda (pembrolizumab), the undisputed class leader in this form of lung cancer.

Libtayo is also under review by the EMA as a treatment for treatment-naïve NSCLC patients with PD-L1 expression of at least 50%, with a decision expected in the second quarter of 2021, according to Sanofi.

Libtayo was the sixth PD-L/PD-L1 inhibitor to reach the market, starting out as a therapy for an uncommon skin cancer called cutaneous squamous cell carcinoma (CSCC), but Sanofi and Regeneron are seeking to expand its use into first-line NSCLC as well as basal cell carcinoma (BCC), another form of skin cancer.

At the moment, the annual net sales of these drugs across all indications are around $25 billion, but about half of that comes from NSCLC, which means even a minor share of that market would be a big step up for Libtayo. Regeneron reported sales of the drug were around $155 million in the first half of 2020.

Keytruda is used mainly in combination with chemo in first-line NSCLC, based on  trial data showing a 51% reduction in death versus chemo alone – although it is also approved as a monotherapy – and has the advantage that it can be given to patients regardless of their PD-L1 status.

Sanofi and Regeneron are hoping that the impressive mortality data from their trial will allow Libtayo to vie for selection as treatment for higher PD-L1 expressors, but other rivals are also in the mix.

Bristol-Myers Squibb’s combination of PD-1 inhibitor Opdivo (nivolumab) and CTLA4 inhibitor Yervoy (ipilimumab) has now been approved by the FDA for two front-line NSCLC indications, both in May.

It was cleared as a monotherapy for patients with PD-L1 levels of 1% or more, and with “limited” chemo in all patients regardless of PD-L1 status, provided they have no EGFR or ALK mutations, which can be treated with targeted drugs.

Meanwhile, Roche’s PD-L1 drug Tecentriq (atezolizumab) has also picked up two approvals from the US regulator, one for the drug on its own in patients whose tumours express PD-L1, and a second alongside chemo in ‘all-comer’ patients with no EGFR or ALK mutations.

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NICE changes stance on Keytruda for first-line head and neck cancer

As recently as June, NICE was minded not to back routine NHS of MSD’s Keytruda as a first-line treatment for advanced head and neck cancer, but it has had a partial change of heart on the drug after the company submitted new data.

Just-published draft final guidance from the cost-effectiveness agency gives a green light for NHS use of Keytruda (pembrolizumab) as a monotherapy for adults with untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) whose tumours express the biomarker PD-L1.

The decision makes Keytruda the first checkpoint inhibitor to be recommended for this use by NICE, according to MSD, which is known as Merck & Co in North America.

NICE hasn’t backed use of the checkpoint inhibitor in combination with chemotherapy however, a decision that the Institute of Cancer Research (ICR) says is disappointing as its experts think there are patients who would benefit more from the combination rather than Keytruda on its own.

The verdict is also at odds with that of the Scottish Medicines Consortium (SMC), which backed both monotherapy and combination use of Keytruda in this setting last month.

ICR would like to see the Keytruda combination available via the Cancer Drugs Fund (CDF), which covers the cost of cancer drugs until confirmatory data is available, for a period of two years in order to allow new evidence to be collected.

NICE however says that while it can support use of Keytruda on its own as the drug is more effective than standard treatments, the cost of using it in combination with platinum chemotherapy and 5-FU “are higher than NICE normally considers an acceptable use of NHS resources”.

ICR’s position is that the decision highlights a major problem with cancer immunotherapies, namely a lack of good tests to determine who will benefit from them.

In this case, biomarker tests like PD-L1 alone “fail to give clinicians a clear-cut indication of who will benefit from immunotherapy – and, critically, who requires pembrolizumab alone and who needs the combination of pembrolizumab and chemotherapy,” it points out.

PD-L1 testing is a “good starting point”, according to ICR’s experts, but “does not allow for the more nuanced approach that is permitted in Scotland and in much of the rest of the world”.

“The partial approval leaves patients in England behind much of the world when it comes to accessing this game-changing treatment,” commented Prof Kevin Harrington of The Royal Marsden, who led the UK arm of the KEYNOTE-048 trial that supported approval of Keytruda in first-line HNSCC.

“The evidence for the benefit of pembrolizumab in combination with chemotherapy in recurrent head and neck cancer is clear – and I would urge NICE and the manufacturer to work together to find a way for patients to access the range of treatment options they deserve,” he added.

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Adult data back Merck’s challenger to Pfizer’s blockbuster Prevnar 13

Merck & Co has built more momentum behind its attempt to depose Pfizer’s blockbuster pneumococcal conjugate vaccine Prevnar 13, with two new phase 3 trials backing its rival shot V114.

The two trials are both in adult subjects, a group that has been driving growth of Prevnar 13 in the last few years, and showed that V114 stimulated immune responses to all 15 pneumococcal serotypes included in the vaccine.

In the PNEU-PATH and PNEU-DAY studies, dosing with V114 was followed a year later by a shot of Merck’s older polysaccharide-based Pneumovax 23 vaccine, and showed that the combination was protective in the over-50 and under-50 adult age groups, respectively.

US-based Merck already has phase 3 data in hand backing the safety and efficacy of V114 in children as well as non-inferiority to Prevnar 13 for the serotypes the two vaccines share. It reiterated its plans to file for approval of the vaccine before the end of the year in the US.

Prevnar 13 – which as its name suggests covers 13 serotypes – is the world’s top-selling vaccine, adding almost $6 billion to Pfizer’s top-line last year thanks to its dominant position in the paediatric pneumococcal shot market.

Added to that, it’s not due to lose patent protection until 2026, when analysts predict it could make more than $7 billion, although it’s worth noting that growth has been pegged back so far in 2020 as a result of the pandemic lockdowns.

Merck is hoping to trump its rival with 15-valent V114, as it provides protection against two serotypes – 22F and 33F – that aren’t included in Pfizer’s product. It also provides an opportunity to expand its position in the adult pneumococcal disease market, where Pneumovax 23 is still widely used.

“Pneumococcal disease in adults is on the rise globally, in part driven by disease-causing serotypes not targeted by the currently available pneumococcal conjugate vaccine,” said Merck’s chief medical officer Roy Baynes.

“These data provide important information about the potential for V114 followed by Pneumovax 23 [which is] included in more than 90% of age-based adult pneumococcal immunization programmes globally,” he added.

Pfizer isn’t resting on its laurels however, and is preparing to defend its Prevnar franchise, reporting positive clinical results with a 20-serotype follow-up – called PF-06482077 or 20vPnC – that it also thinks could be ready for filing before the end of the year.

As a backup it has also been developing a 7-serotype shot that would provide the same breadth of cover as 20vPnC when combined with Prevnar 13.

Pneumococcal disease is caused by Streptococcus pneumoniae, and includes non-invasive illnesses like pneumonia, sinusitis and middle ear infections, as well as invasive diseases like meningitis.

It can be particularly problematic in young children under two and adults aged over 65, as well as people with compromised immune systems.

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Amgen shares down as heart failure drug disappoints in phase 3 trial

Shares in Amgen were down nearly 7% after close of trading yesterday after the company’s heart failure drug omecamtiv mecarbil disappointed in a large phase 3 trial.

Take a look at Amgen’s portfolio and it becomes apparent how important this potential new drug is: the company is relying on its ageing inflammatory diseases drug Enbrel for a large chunk of its revenue.

It is also hoping to steal market share from rivals with biosimilars, which are comparatively cheaper versions of biologic drugs.

Psoriasis drug Otezla is also bringing in the bucks – but Amgen paid $13.4 billion for this after Celgene was forced to sell it as a condition of its merger with Bristol-Myers Squibb.

Amgen looks in need of fresh home-grown revenues, but investors don’t think these will come from omecamtiv mecarbil, based on the findings of the phase 3 GALACTIC-HF trial.

The trial met its primary endpoint by demonstrating a statistically significant effect to reduce cardiovascular death or heart failure events compared with placebo in patients treated with standard care.

But there was no reduction in the secondary endpoint measuring only cardiovascular death in the trial, which with 8,256 patients with reduced ejection fraction in 35 countries is one of the largest phase 3 cardiovascular outcomes studies in heart failure ever conducted.

Adverse events, including major ischemic cardiac events, were balanced between treatment arms, Amgen said.

With such a large cohort of subjects, Amgen and partners Cytokinetics and Servier have nowhere to hide – they cannot claim the trial was not powered to produce a result against this important secondary endpoint measuring the impact on mortality.

Merck & Co and Bayer are trying to develop a rival heart failure drug in patients with reduced ejection fraction, vericiguat, but that has also produced similar results, scoring against a composite measure of deaths and hospitalisation but failing to outperform placebo at reducing deaths.

Developed by Cytokinetics, omecamtiv mecarbil is a cardiac myosin activator that works by increasing interactions between filaments in the heart muscle to improve its pumping.

Amgen has been working on the drug with Cytokinetics since 2006, and Servier bought European rights in 2013.

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Roger Perlmutter leaves Merck after 7 years, joins board at Insitro

Roger Perlmutter has brought a seven-year stint as head of R&D at Merck & Co/MSD to a close, jumping ship to take on an advisory role at machine-learning specialist Insitro.

The 68-year-old – credited with being a catalyst for Merck’s highly lucrative move into cancer immunotherapy – will officially retire from the big pharma company at the end of the year.

He will be succeeded by Dean Li, who is currently Merck’s senior vice president of discovery sciences and translational medicine.

Under Perlmutter’s tenure Merck has been buoyed by the stellar performance of its flagship checkpoint inhibitor Keytruda (pembrolizumab), a PD-1 inhibitor.

The drug has racked up dozens of FDA approvals across more than 15 cancer types, and dominates the treatment of some including the big non-small cell lung cancer (NSCLC) category, and has hundreds of trials still underway to expand its use even further.

Latterly however investors have started to ask whether the company has become a bit too reliant on the drug, which brought in around a third of Merck’s $9.7 billion in pharma sales in the second quarter of this year, particularly as it’s facing patent expiry for diabetes blockbuster Januvia (sitagliptin) in 2023.

Some have suggested that Merck is in danger of following a path trodden by AbbVie, which became far too reliant on its immunology blockbuster Humira (adalimumab) and had to work hard to bring new therapies to market ahead of its patent expiry.

There’s already plenty of evidence that Perlmutter has taken steps to avoid that scenario, in part by adhering to Merck’s longstanding “disease-agnostic” approach to R&D, rather than narrowing its focus to a few core therapeutic categories.

Merck has been raising its R&D budget by a healthy margin over the last few years, already one of the largest in the industry as a proportion of sales, as well as bolting on pipeline drugs and forging key partnerships, such as its alliances with AstraZeneca on PARP Inhibitor Lynparza (olaparib) and Eisai on Lenvima (lenvatinib).

Perlmutter’s departure comes as Merck’s chief executive Ken Frazier has also reportedly delayed his retirement to seek out a new CEO, so Merck could soon be looking at a major transition in its top leadership.

“Since rejoining the company seven years ago, Dr Roger Perlmutter has had a profound impact on Merck and the patients we exist to serve,” said Frazier.

Merck has amassed more than 100 regulatory approvals for its medicines and vaccines globally – including more than 15 novel vaccines and therapeutics – since Perlmutter took the R&D tiller, he pointed out.

“Roger’s legacy will include a rejuvenated research and development organization, staffed by world class scientists, clinicians and professionals,” he added.

Perlmutter is taking an independent seat on the board at South San Francisco-based Insitro, a specialist in applying artificial intelligence to drug discovery that only came out of stealth mode in 2018.

Led by Stanford University AI professor Daphne Koller, Insitro has already signed a major partnership with Gilead in the area of non-alcoholic steatohepatitis (NASH) and raised more than $240 million in venture capital funding, including a $143 million round earlier this year.

“Insitro, with its emphasis on sophisticated data generation and analysis, is strategically positioned to spearhead a new approach to drug discovery that should permit better therapeutics to emerge both more rapidly and at a lower cost,” said Perlmutter.

“As a board member, I am keen to contribute to the realization of this transformative approach to biopharmaceutical R&D,” he added.

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BMS’ Opdivo aces trial in asbestos-linked lung cancer

Bristol-Myers Squibb’s Opdivo has improved survival in a trial involving patients with mesothelioma, a form of lung cancer, getting one up over rival checkpoint inhibitor Keytruda from Merck & Co.

The results of the CheckMate-743 trial showed that a combination of Opdivo (nivolumab) with low-dose Yervoy (ipilimumab) reduced the risk of death by 26% compared to platinum-based chemotherapy after 22 months of follow-up.

The result, reported at the World Conference on Lung Cancer’s virtual congress over the weekend, is the first evidence that immunotherapy combinations can work in mesothelioma, a rare, aggressive cancer that most often affects the lining of the lungs and abdomen after contact with asbestos.

A combination of Eli Lilly’s Alimta (pemetrexed) with cisplatin or carboplatin has been the standard-of-care mesothelioma treatment for more than a decade, but most patients only survive for nine to 12 months after diagnosis.

In CheckMate-743 the median survival for patients on Opdivo/Yervoy was 18 months, compared to 14 months in the chemo group. And after two years, 41% of patients on BMS’ drugs were still alive, compared with 27% of those on chemo.

Last year, Merck’s Keytruda (pembrolizumab) was unable to improve progression-free survival as a second-line treatment for advanced mesothelioma patients after first-line chemotherapy in the PROMISE-meso trial, despite promising results in prior, smaller studies including KEYNOTE-28.

Keytruda is however in a phase 2/3 trial comparing the drug to standard chemo in previously-untreated patients, with results due in 2022.

Meanwhile, there is some crossover between mesothelioma and the recent approval of Merck’s drug in cancers with unresectable disease and high tumour mutational burden (TMB-H). Around 13% of the tumours treated in the KEYNOTE-158 trial, which supported that FDA approval, were mesotheliomas.

CheckMate-743 is great news for patients with mesothelioma, but isn’t likely to be a big opportunity for BMS commercially if Opdivo gets approval in this cancer.

There are only a few thousand cases of the cancer in the US each year – with around 2,700 in the UK which is among the top countries worldwide in terms of incidence. The numbers are falling however as exposure to asbestos is much reduced since it was banned in dozens of countries around the end of the 20th century.

The trial is another boost for BMS’ Opdivo/Yervoy combination though, which has picked up a pair of approvals for first-line non-small cell lung cancer (NSCLC) in recent months that allow it to challenge market leader Keytruda in its biggest indication.

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Roche’s Tecentriq flunks triple-negative breast cancer trial

Roche’s hopes of extending the use of its PD-L1 inhibitor Tecentriq in triple-negative breast cancer (TNBC) have been dashed by a late-stage trial failure looking at the drug in combination with chemotherapy.

Adding Tecentriq to treatment with paclitaxel as a first-line treatment for TNBC patients whose tumours expressed the biomarker PD-L1 did not lengthen the time it took for the cancer to progress, when compared to paclitaxel plus placebo.

Moreover, there was a trend towards worse overall survival with Roche’s drug in the IMpassion131 study, although the company says the data on this are still immature and statistically underpowered.

TNBC is so called because it lacks the biomarkers that other targeted therapies can latch on to.  It is more aggressive than other types of breast cancer, accounting for 15-20% of cases but causing 25% of deaths.

Tecentriq was the first drug among checkpoint inhibitors to get approval in TNBC, although rivals are circling, notably Merck & Co / MSD’s Keytruda (pembrolizumab).

“Today’s results underscore the need to better understand the cancer and immune system interactions, including the chemotherapy backbone and associated regimens,” said Roche’s chief medical officer Levi Garraway.

Roche’s drug is already licensed in more than 70 countries as a front-line treatment for PD-L1-positive forms of TNBC in a regimen with Bristol-Myers Squibb’s Abraxane (nab-paclitaxel) – a form of paclitaxel bound to the blood protein albumin to improve its delivery side effects – based on the IMpassion130 trial.

Tecentriq has had the frontline TNBC immunotherapy market to itself since it was approved last year, but is facing direct competition from Keytruda (pembrolizumab) in the wake of the KEYNOTE-355 trial reported in May.

That study showed Merck’s drug plus chemo reduced the risk of disease progression or death by 35% compared to chemo alone in PD-L1-positive TNBC, and will form the basis of regulatory filings later this year.

There’s little doubt that the arrival of Keytruda on the TNBC market would have an impact on Roche’s ambitions in this area, given the drug is the top-selling PD-1/PD-L1 inhibitor.

Failure in IMpassion131 puts a brake on growth in an indication that Roche has suggested could be worth $1 billion in sales on its own for Tecentriq, which brought in around $2 billion for Roche last year across its approved uses in TNBC, bladder and various forms of lung cancer.

It’s not all been bad news for Tecentriq of late, however. In June, Roche scored a major win for Tecentriq as a pre-surgery (neoadjuvant) therapy for TNBC patients – regardless of their PD-L1 status – on the back of the IMpassion031 trial, and is in the build-up to regulatory filings in this indication.

That would open up a much larger eligible patient population for the drug and extend its use into the 60% of TNBC patients with low PD-L1 expression levels. Merck is lurking in the wings in the neoadjuvant setting too though, thanks to the results of KEYNOTE-522 reported last year.

So far, none of the PD-1/PD-L1 inhibitors have been approved for neoadjuvant or adjuvant (post-surgery) use in any form of cancer.

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Merck & Co to repurpose failed obesity drug for NASH

Merck & Co is to pay $10 million to Hanmi to repurpose an obesity drug discarded by Johnson & Johnson, into a therapy for the fatty liver disease known as NASH.

Non-alcoholic steatohepatitis, as the disease is also known, has been a target for pharma for years but is proving a tough nut to crack as there are no drugs yet approved to treat it.

Intercept was previously the front runner but its obeticholic acid has run into trouble with the FDA, which rejected a filing at the end of June.

Now US-based Merck wants to see if it can get Hanmi’s drug, known as efinopegdutide, to work in NASH after J&J walked away from developing it in obesity.

Metabolic diseases is already a focus area for Merck & Co – it markets several diabetes drugs including Januvia (sitagliptin) and last year exercised an option to develop NGM313, an antibody developed by NGM that could be used in NASH and type 2 diabetes.

J&J handed back rights to Hanmi after efinopegdutide, a once-weekly glucagon-like peptide-1 (GLP-1)/glucagon receptor dual agonist, failed to produce convincing data in clinical trials in obese patients with or without diabetes.

As well as the up front $10 million payment, South Korea’s Hanmi could receive milestone payments up to $860 million if certain development, regulatory and commercial targets are met.

Hanmi could also get double digit royalties on sales if the product is approved and retains an option to market it in Korea.

Dr Sam Engel, associate vice president, Merck clinical research, diabetes and endocrinology, Merck Research Laboratories, said: “Data from phase 2 studies has provided compelling clinical evidence that warrants further evaluation of efinopegdutide for the treatment of NASH.”

NASH is predicted to be an important source of revenues for pharma. Drugs to treat the condition could become blockbusters and the market is expected to be worth $84 billion worldwide according to latest estimates from ResearchAndMarkets.com.

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MSD’s David Peacock on moving UK healthcare forward

David Peacock has worked across the world for MSD and other companies, and has now taken the helm of MSD’s UK & Ireland operations. In the latest article in our UK Leaders series, he tells us about the opportunities and challenges he is excited to take on in the region.

Peacock has had a strikingly international career, including jobs in the US, Australia, Singapore, Vietnam, Japan, and Hong Kong – working across many different roles in various healthcare companies and even setting up his own business, hydration tablet company Nuun.

The UK might seem like a small change after all that, but Peacock said he was “tremendously excited” at the opportunity to be heading up MSD’s business in the region.

“The world watches the UK when it comes to market access, whether that’s in terms of HTA or the commercial relationships that are established with Public Health England and the NHS,” he says.

“The health system continues to move as the NHS and our industry continue to adapt. Through that process of adaptation, MSD in the UK has led trends for the company globally. I was very excited about having the opportunity to come in and work with a group that has this reputation for embracing new ideas.”

Peacock says his goal coming into the company is to maintain that reputation and build “true partnerships” with the NHS.

“The NHS is a large organisation to change. Getting people aligned, not just in their understanding, but also in their beliefs, is hard.”

“I recognise that I’m coming into the UK when the country is dealing with affordability challenges,” he says. “One of my goals is to understand how this healthcare system is operating, and what challenges it is facing.

“I’m a true believer in partnership and collaboration. What I’m looking for, as I come into this business, is how we can continue to move past the traditional promotional models – like simply pushing messages out to clinicians that represent the risks and benefits associated with our products.

“Those models worked for many years, but they’re not going to be good enough going forward. We need to move past being suppliers to healthcare systems towards becoming true partners. We have skills, expertise, and assets that we can bring to bear to help solve the NHS’ problems. My goal coming into the UK is really to keep us on the path to achieving that.”

Bringing pharma and the NHS together

Luckily, Peacock says that the foundations of this kind of thinking are there for MSD and the NHS to build upon, and he has seen “bright spots” in the health service where these kinds of partnerships already exist.

“The joint working opportunities in the NHS are fantastic – we can go into a meeting space with the NHS and clearly put on the table that we want to work together to solve a problem. That framework doesn’t really exist in most of the world; there is real intent for partnership here.”

Peacock adds that if the sector is to truly solve issues around achieving better patient outcomes, we will need more forums where we can bring together a multitude of partners.

“We have to bring in not just pharma and the NHS but also other industries and patient groups, and tackle problems in a systematic way. At the moment we tend to focus on a particular capacity constraint.”

He says that the patient voice in particular is central to this – especially when both health systems and pharma share the goal of saving and improving lives.

“I don’t view our industry as majorly competitive because we’re all aiming at that same goal. We may use different words, but we’re completely aligned on it.

“The focus is on the patient, so we can’t look at them in a detached manner – we have to actually engage and understand their circumstances, their wants and needs, and their environments. The only way that we can really do that is to directly engage with patient organisations.

“Ultimately, we want them to guide us. I think the NHS wants the same. We just have to figure out a way to connect all these pieces together.”

Peacock says enthusiasm for change from the NHS’ side can vary depending on where you look – although there are pockets of great progress.

“I have certainly talked to people in the NHS who are passionate, who are frustrated and, equally, are hopeful. The NHS is on its own journey, with its own long-term plan. I’m fully supportive of the efforts they’ve got underway, but it’s a large organisation to change. Getting people aligned, not just in their understanding, but also in their beliefs, is hard.”

And from MSD’s side of things, Peacock says that it is important the company considers how its internal structures and its employees can contribute to better collaboration.

“We need to make sure that we have the people, the mindsets, and the skillsets for collaboration, so that when we engage with the system, we’re able to articulate the value that we bring in a way that is not seen as just being self-promotional. That takes time, though, because the reality is that it hasn’t been the operating model for most of the industry’s lifespan.

“It will involve reviewing how we incentivise our people, how we recruit, and how we allow employees to get a broader perspective. Traditionally, people have focused their careers on one area, e.g. commercial, R&D, medical, etc. We need to look at how we can create opportunities for people to move across those boundaries.

“We’ll still need specialists, of course, but we also want generalists who have familiarity with different types of problems and how to solve them.”

Progress during COVID-19

In some ways, he says, the COVID-19 pandemic has set back this progress – and the industry will need to think about how it engages with the NHS to get them back on track – but in other ways, the crisis has accelerated such thinking.

“We’re certainly seeing more people looking at things from an end-to-end perspective. The crisis has forced the system to actually look holistically and break down some of the silos that exist within the NHS to drive better patient outcomes.

“When we were providing products that were needed in ICUs, the NHS was quickly able to break down barriers, work directly with us to source and supply from global outlets all over the world, and bring in the MHRA to provide regulatory support to enable products to flow directly into the country and straight into the hospitals. The speed at which we did that was astounding – things that would normally take us a year were happening within 48 hours.

“That shows the NHS can move rapidly when there’s purpose. My hope is that we can build on these initial stages and make it real. We just don’t want to go back to those old ways where it’s committee after committee after committee.”

In general, though, Peacock says he remains excited about the future of the UK ecosystem.

“The UK has so many opportunities – a single health system, a single payer  environment, and an immense amount of data and scientific publications. All the pieces are in place now – we just need to look at how we can tie them together.

“People should feel positive. What we need to do now is help the people who have these dreams to realise a better future.”

About the interviewee

David PeacockDavid Peacock is currently serving as the managing director for MSD in the UK and Ireland, having taken up his position in 2019. Prior to this David served as the chief of staff for the office of the chairman, president and CEO of Merck & Co. Over the course of his career with MSD David has gained a broad set of leadership experiences including serving as the CFO for MSK K.K. in Japan, leading the company’s business in Hong Kong & Macau, and successfully delivering in a variety of other commercial roles based in Japan, Vietnam, Singapore, and the United States.

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Controversy as pharma execs predict profits from COVID-19 vaccines

Concerns have emerged about access to some potential COVID-19 vaccines after pharma executives from three companies said they expect to make profits from their products in evidence to a US Congressional panel.

Moderna, Merck & Co, and Pfizer said they expect to profit from coronavirus vaccines if they are approved, although AstraZeneca and Johnson & Johnson said they will price their respective vaccines only to cover costs if they are approved.

The hearing was discussing the efforts to develop a safe, effective, and accessible vaccine against COVID-19.

US-based Moderna is in mid-stage clinical development, making it one of the front-runners in the race to develop a vaccine against the SARS-CoV2 virus that causes COVID-19.

Along with AstraZeneca, Moderna has received funding from the US government to help develop its vaccine, although Pfizer has not.

The funding would make any profits controversial, something that lawmakers addressed in their conversations with the pharma representatives, who attended the hearing via a video link.

Merck & Co’s vaccine has yet to enter the clinic, but the company’s considerable financial clout and the accelerated development timelines for COVID-19 vaccines mean this could change very quickly.

Julie Gerberding, chief patient officer for US-based Merck told the House of Representatives subcommittee on oversight and investigations: “We will not be selling our vaccine at cost, although it is premature for us as we’re a long way from understanding the cost-basis.”

Reuters reported that Gerberding and a representative from Moderna did not comment on the price they have in mind for their vaccines at the hearing.

Representing Pfizer, chief business officer John Young said that the company intends to make a profit from its vaccine, developed in partnership with Germany’s BioNTech, if it gets approved.

Young said: “We recognize that these are extraordinary times and our price will reflect that.”

Pfizer and BioNTech have reported promising early results from their vaccine and are preparing for late-stage trials, scheduled to begin in the coming weeks.

Jan Schakowsky, Democrat representative from Illinois who sits on the committee, was clearly unimpressed by some of the responses, particularly from Pfizer.

There are now 24 potential vaccines in clinical development, with the World Health Organization listing several phase 3 products developed in China as the most advanced.

AstraZeneca is close behind, and is hoping to have its vaccine ready by the end of the year after favourable early data from a phase 1 clinical trial announced earlier this week.

Feature image courtesy of Rocky Mountain Laboratories/NIH

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FDA grants fast review for Bayer/Merck & Co’s heart failure drug

The FDA has granted a faster Priority Review for Bayer and Merck & Co’s filing for vericiguat, which is being developed for chronic heart failure with reduced ejection fraction, following a previous heart failure event. 

US-based Merck, known as MSD outside North America, has been developing vericiguat with ejection fraction less than 45% following a worsening heart failure event. 

Filing was based on data from the phase 3 VICTORIA study and the Priority Review tees up a potential approval within six months instead of the standard 10-month timeframe. 

The FDA has set a decision date of January 20, 2021. 

Merck & Co paid Bayer $1 billion in 2016 for US rights to the drug, which if approved could be a competitor to Novartis’ blockbuster Entresto (sacubitril+valsartan). 

The companies are jointly developing the soluble guanylate cyclase (sGC) stimulator, and in 2016 took a gamble by pushing it into phase 3 development despite mixed results at phase 2. 

VICTORIA met its composite primary endpoint when vericiguat reduced risk of heart failure hospitalisation or cardiovascular death in patients with worsening chronic heart failure with reduced ejection fraction, when added to available heart failure therapies and compared with placebo. 

However it emerged when detailed data were revealed from the 5,050-patient trial a few months later that the composite endpoint was met mainly thanks to a statistically significant reduction in risk of hospitalisations of 10%. 

There were 7% fewer deaths in the trial treated with the drug, but that result was not statistically significant. 

Secondary endpoints include time to occurrence of cardiovascular death, time to first occurrence of heart failure hospitalisation, time to total heart failure hospitalisations (including first and recurrent events), time to the composite of all-cause mortality or heart failure hospitalisation, and time to all-cause mortality. 

Merck and Bayer are also trialling vericiguat in heart failure with ejection fraction at phase 2 – an indication where Novartis’ Entresto surprisingly flopped in a phase 3 trial.

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AstraZeneca and Merck & Co’s Lynparza Receive the US FDA’s Approval as a 1L Maintenance Treatment of Germline BRCA-Mutated Metastatic Pancreatic Cancer

Shots:

  • The approval follows the US FDA Oncologic drugs Advisory Committee (ODAC) on 17 Dec based on P-III POLO trial, which involves assessing of Lynparza tablets (300 mg bid) as maintenance monothx vs. PBO in 154 patients in ratio (3:2) with gBRCAm metastatic pancreatic cancer whose disease had not progressed on at least 16 weeks on 1L Pt-based chemotherapy
  • The study resulted in improvement in median progression-free survival (7.4 mos. vs 3.8 mos.), 47% reduced risk of disease progression or death, respond ratio (23% vs 12%), median duration of treatment in excess of 2 yrs. (24.9 mos. vs 3.7 mos.), OS (18.9 mos. vs 18.1 mos.), safe and tolerable
  • AstraZeneca and Merck & Co’s (MSD outside the United States and Canada) Lynparza (olaparib) is a first-in-class PARP inhibitor targeted to block DNA damage response (DDR) in cells/tumors harboring a deficiency in homologous recombination repair (HRR) and is approved in 65 countries

Click here to read full press release/ article | Ref: AstraZeneca | Image: Signbox