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This news from the FDA followed a resubmission after the FDA’s complete response letter for the P2X3 receptor antagonist’s use in refractory chronic cough and unexplained cough.
An advisory committee of the US Food and Drug Administration (FDA) voted 12-1 against an approval of Merck & Co.'s drug known as gefapixant, a P2X3 receptor antagonist formulated as a treatment for chronic cough in adult patients.1
This vote decision, opposed by Merck, was conducted in the first place to provide guidance to the FDA in its upcoming decision on the drug’s approval, slated for December 27. The noted lack of FDA-approved treatments for chronic cough suggests a lack of regulatory precedent for the indication.
This vote by the advisory committee follows a decision from 2022 in which a complete response letter (CRL) from the agency was issued for gefapixant's use among adult patients with refractory chronic cough or unexplained cough.2 Merck ended up putting forward a new application for the FDA’s approval.
The company’s resubmission was based upon fresh analyses due to the FDA's request for further efficacy data. This revised submission represented a notable delay for the biopharmaceutical company, given their initial anticipation for approval of gefapixant in 2021.
Merck also modified its cough-counting system when examining effectiveness of the drug, but the FDA found it to be challenging as far as determining clinical significance. The agency conducted its post hoc analysis, demonstrating only small differences in median cough frequency between treatment arms.
“I don’t think the level of evidence supports that the drug makes a significant difference. It’s unfortunate,” Mark Courey, MD, vice chair of quality for otolaryngology and head and neck surgery at Grabscheid Voice and Swallowing Center at Mount Sinai, said in a statement.
Courey’s statement reflected some of the concerns of the FDA and the other advisory committee members.
“I am concerned that if the drug is readily available, it could lead to a delay in diagnosis of other illnesses because cough—while it can be very debilitating—is a symptom, not a disease in and of itself,” Courey noted in the statement. “And so, I think this would delay the evaluation of the patients for other diseases that could be potentially harmful.”
The program, including the P030 and P027 studies, led to results showing a statistically significant reduction in cough frequency in P030 (p-value 0.03) as well as a borderline result in P027 (p-value 0.057).
Questions were noted regarding the decisions on endpoints. Some committee panelists indicated that the lack of a coughing fits measurement and Merck responded noting that there is a lack of an agreed-upon clinical definition for a cough cluster.
A patient representative suggested, however, that she was “greatly” on the fence regarding the decision about gefapixant. Additionally, the meeting featured a discussion with chronic cough patients in which the pain, inconvenience, and general difficulty of testing were touched upon.
These individuals emphasized the value of a potential treatment for chronic cough in the future as far as quality of life improvements.