UPDATED: FDA says it needs a little more time to decide on Merck's P2X3 for chronic cough
A few months ago, Merck emerged as a clear leader among a group of drugmakers racing through the clinic with a new class of therapies for chronic cough. But it looks like the Kenilworth, NJ-based pharma will now be taking another lap.
The FDA is delaying its decision on Merck’s gefapixant by at least a few months to “provide time for a full review of the submission,” the company revealed in an SEC filing. The agency, which originally set a PDUFA date for Dec. 21, now expects to make a decision by March 21.
Gefapixant is one of a few P2X3 receptor antagonists competing in the refractory chronic cough setting, including candidates from Bayer and Shionogi. But after Merck’s chief rival Bellus flopped in a Phase II trial last summer, it could be anyone’s game.
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.
Gefapixant missed a secondary endpoint of awake coughs per hour in COUGH-1, but the higher dose reached statistical significance in COUGH-2. Investigators also flagged high dropout rates due to adverse events, including taste-related side effects, which were experienced by more than half of patients given the higher dose in both trials, compared to under 10% of patients in the placebo arms.
Bellus’ pitch centers on a more selective approach that avoids taste-altering side effects — but in a mid-stage study, all four doses of BLU-5937 fell short of the mark for placebo-adjusted reductions in coughing. In a Phase IIb study, the company’s enrolling patients with a baseline awake cough frequency of ≥25 awake coughs per hour, where data suggest the drug will have a better chance.
Bayer’s eliapixant met the primary endpoint in a Phase IIb study earlier this month, significantly improving 24-hour cough frequency (though the company has yet to release hard data). Shionogi’s sivopixant is in an ongoing Phase II study, according to its website.
Merck’s Roy Baynes has big plans for gefapixant as a potential “pipeline in a product.” After buying Afferent Pharma and its P2X3 platform for $500 million upfront in 2016, the company plotted a whole range of programs in endometrial-related pain, sleep apnea and other sensory related functions.