Research & Development
US FDA Accepts US Merck's Gefapixant New Drug Application for Review
2 March 2021 - - The US Food and Drug Administration has accepted for review US-based pharmaceutical company Merck's (NYSE: MRK) New Drug Application for gefapixant, an investigational, orally administered, selective P2X3 receptor antagonist, for the treatment of refractory chronic cough or unexplained chronic cough in adults, the company said.

This application for gefapixant will be discussed at an upcoming advisory committee meeting. No date has been set yet.

The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action date, of Dec. 21, 2021.

The NDA is based on results from the COUGH-1 and COUGH-2 clinical trials, which are the first companion Phase 3 studies ever conducted in patients with RCC, a cough that persists despite appropriate treatment of underlying conditions, or UCC, a cough where the underlying cause cannot be identified despite a thorough evaluation.

Data from COUGH-1 and COUGH-2 were presented at the virtual European Respiratory Society International Congress 2020.

COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) are Phase 3 multinational, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of gefapixant in reducing cough frequency in adult participants with refractory chronic cough or unexplained chronic cough.

A total of 2,044 participants were treated in COUGH-1 (n=730) and COUGH-2 (n=1,314). In both studies, patients were randomly selected to receive one of the following: gefapixant 45 mg twice daily, gefapixant 15 mg twice daily, or placebo.

The primary efficacy outcomes measure for COUGH-1 and COUGH-2 were 24-hour cough frequency at week 12 and 24-hour cough frequency at week 24, respectively, measured using an ambulatory digital audio recording device.

Secondary endpoints in both trials included awake coughs per hour and percentage of participants with a greater than 1.3-point increase from baseline in the Leicester Cough Questionnaire total score.

COUGH-1 had a 12-week treatment period and a 40-week extension period, while COUGH-2 had a 24-week treatment period and a 28-week extension period.

Gefapixant is an investigational, orally administered, selective P2X3 receptor antagonist, for the potential treatment of refractory or unexplained chronic cough.

P2X3 receptors are one of the receptor types found on sensory nerve fibers, predominantly C fibers, in the airway lining. Chemical stimuli, including adenosine triphosphate, can be released from airway lining cells due to airway inflammation, irritation and mechanical stress/injury.

Binding of extracellular ATP to P2X3 receptors on C fibers in the airway can be sensed as a signal of potential damage, creating an action potential, which may initiate coughing. The inhibition of binding of extracellular ATP to P2X3 receptors is thought to reduce sensory nerve activation and, subsequently, cough.

The prevalence of chronic cough (a cough lasting more than eight weeks) is estimated to be approximately 5% of adults in the US In a subset of these cases, patients either do not respond to treatment of underlying conditions (such as asthma or gastroesophageal reflux), known as refractory chronic cough, or they have no identifiable underlying condition despite a thorough evaluation, known as unexplained chronic cough.

There are currently no approved therapies for the treatment of RCC or UCC.