In a decisive vote, the FDA’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) rejected the approval of gefapixant, a Merck-developed drug intended for the treatment of chronic cough, citing marginal clinical benefits over placebo. The committee’s 12-1 vote on Friday reflects skepticism about the drug’s efficacy in providing a clinically meaningful benefit to adult patients with refractory or unexplained chronic cough (RCC/UCC).
Chronic cough, persisting for over eight weeks without a clear diagnosis, and RCC, where the cough persists despite treatment for diagnosed conditions, both lack approved therapies. Merck’s gefapixant, a P2X3 receptor antagonist, aimed to fill this therapeutic void. However, the FDA panel was unconvinced by the drug’s modest 14-18% reduction in cough frequency compared to placebo, questioning the clinical significance of such improvement.
Merck’s Joerg Koglin, SVP of Global Clinical Development, expressed disagreement with the committee’s conclusion, citing “strong, comprehensive data” demonstrating gefapixant’s meaningful clinical benefit. Nonetheless, the PADAC’s decision was influenced by the minimal efficacy difference between gefapixant and placebo, as well as inconsistencies between primary and secondary trial endpoints.
The sole affirmative vote came from a patient advocate on the committee, highlighting the need for treatments in this area. The discussion also pointed to the inadequacy of mean or median cough reductions as measures of patient benefit, suggesting that future chronic cough trials require different study designs and endpoints that more accurately capture the patient experience.
Participants in the placebo group also exhibited a reduction in cough frequency, which could indicate either a natural resolution of RCC and UCC over time or a placebo effect induced by the trial. Merck noted that placebo effects are common in cough trials due to the nervous system’s role in coughing, referencing similar observations in previous codeine trials.
Adding to the drug’s challenges, patients reported loss of taste, a known side effect of P2X3 inhibitors, which could further limit its desirability as a treatment option.
While the FDA is not obligated to follow the advisory committee’s recommendations, it typically considers such input. With gefapixant’s decision date set for December 27, following a previous non-approval last year, the drug’s future remains uncertain.
As the pharmaceutical industry continues to evolve, the importance of strategic planning and the integration of digital technologies and data analytics is underscored. These tools are essential for gaining insights into patient health and optimizing the impact of health interventions, such as through targeted TV campaigns that can enhance prescription uptake.
