FDA rejects MSD’s gefapixant for chronic cough

The US Food and Drug Administration (FDA) has declined to approve MSD’s gefapixant for the treatment of refractory chronic cough (RCC) or unexplained chronic cough (UCC) in adults.

The issuing of a complete response letter (CRL) by the agency to MSD’s new drug application (NDA) was related to a lack of substantial evidence of the drug’s effectiveness for treating the condition that affects 5% to 10% of adults in the US, according to a 20 December press release.

The rejection follows an FDA advisory committee meeting last month, where the panel voted 12-1 against the clinical evidence of gefapixant submitted by MSD. The panel itself was just after the FDA published briefing documents demonstrating little difference between the placebo group and the gefapixant group from a trial.

MSD said that the CRL was not related to gefapixant’s safety, adding that it is now reviewing the FDA’s feedback to determine the next steps.

This is the second FDA rejection for gefapixant. In January 2022, the FDA issued a CRL to the pharma company asking for more efficacy data.

Gefapixant was approved in Japan in 2022 for adults with refractory or unexplained chronic cough, where it is marketed as Lyfnua. The drug was authorised by the European Medicines Agency (EMA) for the same indication in September 2023.

The FDA not following suit opens the US chronic cough market door to GSK’s candidate camlipixant. The British pharma company added camlipixant to its pipeline when it acquired Canada-based Bellus Health for $2bn in April 2023. Camlipixant is currently in Phase III clinical development and is slated for regulatory approval and launch in 2026.

There are currently no FDA-approved therapies for chronic cough – defined as a cough that lasts more than 8 weeks.

Both gefapixant and camlipixant are P2X3 antagonists. It is believed that P2X3 rechronicceptors are responsible for chronic cough.

MSD said 45mg gefapixant twice daily demonstrated a statistically significant reduction in 24-hour cough frequency in two 52-week, multinational, randomised, double-blind, placebo-controlled studies referred to as P027 (NCT03449134) and P030 (NCT03449147). Additional data submitted to the FDA on NDA resubmission was based on a re-analysis of a cough-counting system.

Merck Research Laboratories’ senior vice president, global clinical development, Dr. Joerg Koglin said: Acknowledging the absence of any approved treatments for refractory or unexplained chronic cough, we are disappointed in the FDA’s response to our application for gefapixant.”

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