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FDA rejects Merck cough drug NDA, briefly weighing on Bellus

By Richard Staines

Jan. 24, 2022

Merck & Co Inc. has had a setback with its chronic cough drug gefapixant after the FDA rejected its NDA, a decision that also briefly hit the share price of rival Bellus Health Inc. before it regained market traction late Jan. 24. The FDA had been reviewing gefapixant since March 2021, but the regulator is now asking for additional information related to measurement of efficacy in a dreaded complete response letter. Merck said the response was not related to the safety of gefapixant, a P2X3 receptor antagonist, under development for treatment of refractory chronic cough (RCC) or unexplained chronic cough in adults. Shares in Merck (NYSE:MRK) ticked down 1.4% to $78.86 while Bellus Health shares (NASDAQ:BLU) rose by 1.8% to $5.66.

Roy Baynes, senior vice president and head of global clinical development, said Kenilworth, N.J.-based Merck remains “committed” to continuing development of gefapixant. The company is reviewing the letter and will meet with the FDA to discuss next steps.

Stuart Green, vice president and therapeutic area head for late-stage clinical development for respiratory and immunology at Merck Research Laboratories, told BioWorld, “At this time, we do not believe additional clinical trials will be necessary to satisfy the questions raised in the CRL.”

Green said it would be “premature” to provide timings for a potential new review with the FDA.

Analyst Josh Schimmer of Evercore said there were two potential explanations for the CRL based on the minimal information released by Merck.

Phase III data showed a reduction in cough frequency of around 20% – a treatment effect that may not have been strong enough as the FDA has no clear threshold for cough reduction. Data may have not held up after sensitivity or unblinding analyses, he added.

The FDA may require more dose-finding work as a 15mg dose wasn’t effective and there were also high rates of taste disturbance – around 60% – with 15% of patients discontinuing treatment.

Bellus readthrough?

Bellus of Laval, Quebec is also having trouble developing a P2X3 receptor antagonist in chronic cough – its potential rival BLU-5937 failed in a phase II trial in July 2020.

Despite that, the company managed to stay in the game with positive phase IIb trial results in RCC announced late last year and has since raised $200 million with its dual Toronto Stock Exchange/Nasdaq listing to fund further development.

Schimmer said there were positives and negatives for Bellus from today’s announcement. Bellus may learn from any additional data produced by Merck, which could struggle to market gefapixant because of its “modest profile”.

However, weighing against Bellus is the lack of clear threshold for chronic cough drugs and a lack of urgency to approve them. BLU-5937’s profile could also be diminished by pending phase III trial data and Bellus may have more work to do on dosing, Schimmer said.

Nerre opted for rare disease focus

Merck’s troubles follow Nerre Thrapeutics Ltd. July announcement that it was taking another shot at showing its chronic cough treatment was effective in July last year.

A £20 million ($27.6 million) funding round allowed the Stevenage, U.K.-based biotech to run a second phase II trials of its neurokonin1 antagonist orvepitant.

The second trial had a different patient-focused primary outcome of chronic cough caused by idiopathic pulmonary fibrosis.

Nerre chose a rare disease indication for orvepitant after it failed to meet the endpoint of reducing awake cough frequency in an all-comers phase IIb trial of 315 patients with refractory chronic cough.

Last week, Japan’s Ministry of Health, Labour and Welfare approved gefapixant under the brand name Lyfnua for adults with refractory or unexplained chronic cough.

https://www.bioworld.com/articles/515387-fda-rejects-merck-cough-drug-nda-briefly-weighing-on-bellus