Gefapixant is a selective P2X3 receptor antagonist being currently developed by Merck for chronic unexplained cough. Chronic cough is a significant issue for many patients. It is estimated that between 5-10% of the population has it at one time. Many patients with chronic cough have underlying allergies that cause post nasal drip, asthma or acid reflux disease. But some patients have no explanation for their coughs after extensive testing. The coughs can be triggered by “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.
We discussed cough in several blog posts in the post extensively, to read more click below on the links: Chronic cough is defined as a cough that lasts more than 8 weeks duration. For patients with underlying diseases it is called refractory chronic cough, for patients with no cause, it is called unexplained chronic cough.
Gefapixant would be administered as a 45mg tablet dosed at twice daily. P2X3 receptors are one of the receptor types found on sensory nerve fibers, predominantly C fibers, in the airway lining. Blocking them is thought to reduce sensory C fiber activation and subsequently, coughing.
For gefapixant, the FDA is basing its decision on some mixed data from two Phase III trials dubbed COUGH-1 and COUGH-2. Researchers linked the 45 mg dose to an 18.5% estimated relative risk reduction in 24-hour cough frequency in COUGH-1, meeting the primary endpoint (p=0.041). In COUGH-2, the same dose led to a 14.6% relative risk reduction (p=0.031). The 15 mg dose, however, failed in both trials.
If you suffer from chronic cough, it is important to try and first determine the cause of it before taking a medication such as gefapixant. Only after testing is done and meeting with your doctor, a medication such as gefapixant should be used.
There is no current branded name yet for gefapixant and the cost of the medication has not been determined yet. If the FDA does approve gefapixant, please check back for more information on it.
Update August 20, 2022
Building on prior phase 2 studies, an article published in The Lancet examined the efficacy of gefapixant in the first phase 3 randomzied placebo controlled trials. Compared to placebo, gefapixant reduced cough frequency when administered at the 45 mg twice-daily dose. It was well tolerated over 52 weeks.