The U.S. Food and Drug Administration issued a Complete Response Letter to Merck & Co. for its New Drug Application for gefapixant for refractory chronic cough or unexplained chronic cough.
Here’s why Merck remained committed to the chronic cough drug gefapixant. (Kena Betancur/Getty Images)
The U.S. Food and Drug Administration issued a Complete Response Letter to Merck & Co. for its New Drug Application for gefapixant for refractory chronic cough or unexplained chronic cough. The drug is a non-narcotic, oral selective P2X3 receptor antagonist.
The rejection was not related to the safety of the drug, although Merck did not specify details from the CRL. The company said it was reviewing the letter and planned to meet with the FDA to discuss the next steps.
Reasons for Merck’s Commitment to Chronic Cough Drug
“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,” said Dr. Roy Baynes, senior vice president and head of Global Clinical Development, chief medical officer, Merck Research Laboratories. “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.”
However, last week, the drug was approved in Japan under the brand name Lyfnua.
The FDA initially accepted the NDA on March 1, 2021. The NDA was built on data from the COUGH-1 and -2 studies, the first companion Phase III trials conducted in patients with RCC. A total of 2,044 patients were treated in the trials. Participants were randomly chosen to receive either 45 mg twice a day of gefapixant, 15 mg twice a day, or placebo. The primary efficacy measures were 24-hour cough frequency at week 12, and 24-hour cough frequency at week 24 for COUGH-1 and COUGH-2, respectively. The cough frequency was measured using an ambulatory digital audio recording device.
The secondary endpoints in both studies included awake coughs per hour and the percentage of patients with more than a 1.3-point increase from baseline in the Leicester Cough Questionnaire (LCQ) total score. There was a 12-week treatment period for COUGH-1 and a 40-week extension period. COUGH-2 had a 24-week treatment period and a 28-week extension period.
“COUGH-1 and COUGH-2 are the first companion Phase III trials in refractory or unexplained chronic cough, underscoring Merck’s commitment to fully researching the potential for gefapixant in this patient population,” Baynes said in a September 8, 2020, statement. “Both trials met the primary endpoint at the 45 mg twice daily dosage, significantly reducing cough frequency in these patients, and we are grateful for the opportunity to share these data with the scientific community.”
According to estimates, between 5% and 10% of adults worldwide suffer from chronic cough. A subset has a refractory or unexplained chronic cough and seems more sensitive to triggers that otherwise healthy people don’t have.
“These include everyday things such as talking, laughing, a change in air temperature or exposure to aerosols or food odors, and to date treatment options are extremely limited for these patients,” said Dr. Lorcan McGarvey, clinical professor, Wellcome-Wolfson Institute of Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast. “Given the significant unmet need for these patients, we are strongly encouraged by the findings of COUGH-1 and COUGH-2 and the potential for a new therapeutic option for patients who are struggling with the burden of this disease, often for many years without relief.”
