Pharma, BioPharma

FDA rejects Merck chronic cough drug, asks for more info on efficacy

Merck is still at the front of the pack of companies developing new medicines to treat chronic cough, but the company was dealt a setback as the FDA turned down the pharma giant’s application and asked for additional efficacy data. No safety issues were raised, according to Merck.

 

A Merck drug that takes a novel approach to treating chronic cough has been rejected by the FDA as the agency called on the company to provide more information about the product candidate’s efficacy.

The request for more data was stated in the FDA’s complete response letter, Merck said on Monday. These letter are not public documents. According to the Kenilworth, New Jersey-based pharmaceutical giant, the agency raised no concerns about the experimental drug’s safety. Merck said it is reviewing the letter and plans to meet with the agency to discuss it.

Chronic cough is a cough that lasts for more than eight weeks. According to Merck, these coughs affect about 5% of U.S. adults. In some cases, the coughing in these patients does not respond to treatment of an underlying condition, such as asthma or gastroesophageal reflux. This type of cough is called refractory chronic cough. In other cases, the cause of the cough cannot be determined. There are no FDA-approved therapies for treating either type of cough.

Gefapixant is a small molecule designed to selectively block P2X3, receptors in the airway that are associated with the cough mechanism. The Merck drug application was based on results of two Phase 3 clinical trials enrolling patients with refractory chronic cough or unexplained chronic cough. Those studies evaluated two doses: 45 mg twice daily and 15 mg twice daily. In the high dose group, Merck reported a statistically significant reduction in cough frequency compared to a placebo at the 12-week mark. The lower dose did not meet efficacy goals in either of the two Phase 3 studies. The clinical trial results were presented in 2020 at the virtual European Respiratory Society International Congress meeting.

Merck added gefapixant to its pipeline through the 2016 acquisition of Afferent Pharmaceuticals. The pharma giant paid $500 million up front and pledged another $750 million tied to the achievement of milestones. Last week, gefapixant was approved in Japan for treating refractory or unexplained chronic cough The drug will be marketed there under the name “Lyfnua.” Gefapixant is still under regulatory review in other markets.

“We remain committed to advancing gefapixant for patients with refractory or unexplained chronic cough and will work with the FDA to address the agency’s feedback,” Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said in a prepared statement. “We believe there is a significant unmet need to help patients manage their chronic cough, as there are no available treatment options indicated in the U.S. specifically for this condition.”

Merck has competitors in the chase for a chronic cough treatment, some of them targeting P2X3. Last summer, Bayer reported its experimental P2X3-targeting small molecule, eliapixant, met the main goal of a mid-stage study evaluating the drug in patients with refractory chronic cough. Bellus Health’s P2X3-targeting small molecule, BLU-5937, has also posted strong mid-stage clinical trial results. The Laval, Quebec-based biotech expects to begin a Phase 3 clinical trial in the second half of this year. A once-daily formulation of the drug is in preclinical development.

There are other companies developing chronic cough drugs that address different targets. New Haven, Connecticut-based Trevi Therapeutics’ small molecule Haduvio blocks the mu opioid receptor and activates the kappa opioid receptor as a way to address chronic cough associated with idiopathic pulmonary fibrosis (IPF), a lung disorder. Algernon Pharmaceuticals aims to treat chronic cough by repurposing ifenprodil, an old Sanofi drug that the pharma giant had commercialized for peripheral circulatory disorders. That biotech is in early-stage development for treating chronic cough associated with IPF. Startups are also joining the mix. GlaxoSmithKline spinout Nerre Therapeutics is developing orvepitant, a small molecule that blocks the neurokinin-1 receptor, as a treatment for IPF-associated chronic cough.

Photo: Christopher Occhicone/Bloomberg, via Getty Images

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