The regulator’s Complete Response Letter on Wednesday said Merck’s data package for gefapixant “did not meet substantial evidence of effectiveness.” The FDA also rejected the drug in 2022 due to a lack of efficacy evidence.
Pictured: Merck Research Laboratories building in California/iStock, hapabapa
For the second time in nearly two years, Merck has failed to secure regulatory approval for its chronic cough drug gefapixant.
In a Complete Response Letter issued Wednesday, the FDA said that Merck’s data package for gefapixant “did not meet substantial evidence of effectiveness” for the treatment of refractory chronic cough (RCC) or unexplained chronic cough (UCC) in adults. The regulator did not point to safety issues related to the drug candidate.
Joerg Koglin, senior vice president of global clinical development at Merck Research Laboratories, said in a statement that the company is “disappointed” by the FDA’s decision, adding that there is currently a “significant unmet medical need” in the field of chronic cough and an “absence of any approved treatments for refractory or unexplained chronic cough.”
The pharma giant will review the FDA’s letter and feedback to determine the next steps for gefapixant, according to Wednesday’s announcement.
Gefapixant is an orally available P2X3 receptor antagonist that works by preventing the signaling cascade in the airways that culminates in a cough reflex. Merck first tried for an FDA approval in 2021 but was ultimately rejected in January 2022. Despite the regulatory speedbump, Merck said at the time that it remained “committed” to gefapixant’s development.
However, Merck’s resubmission was similarly met with strong skepticism from the FDA. In a briefing document released ahead of a November 2023 advisory committee meeting, the regulator’s reviewers still found the efficacy data for gefapixant to be underwhelming. Treatment “showed a small reduction in cough frequency,” according to the reviewers, who were uncertain whether gefapixant’s effects were clinically meaningful or not.
A few days later, the FDA’s Pulmonary-Allergy Drugs Advisory Committee shared the same concerns and voted 12-1 against gefapixant.
Gefapixant’s regulatory stumble on Wednesday continues the industry’s losing streak in the chronic cough space. In February 2022, Bayer discontinued the Phase II development of eliapixant, which is also a P2X3 receptor antagonist, following its disappointing benefit-risk profile. Eliapixant was being developed for RFC, overactive bladder, endometriosis and diabetic neuropathic pain.
Seeking to take advantage of this void in the marketplace, GSK in April 2023 signed a $2 billion contract to acquire Bellus Health, gaining access to its cough candidate camlipixant. In December 2021, the candidate aced the Phase IIb SOOTHE trial, eliciting strong reductions in cough frequency versus placebo.
Like gefapixant and eliapixant, camlipixant is a P2X3 receptor agonist and has best-in-class potential, according to GSK.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
