Merck New Drug for Chronic Cough: Gefapixant Faces Second FDA Rejection

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Merck New Drug for Chronic Cough: Gefapixant Faces Second FDA Rejection

Merck New Drug for Chronic Cough, Gefapixant Faces Second FDA Rejection, Losing Lead

After a second rejection by the FDA, Merck’s new drug for chronic cough, Gefapixant, is facing an increasingly uncertain future in the United States.

Gefapixant, developed by Merck as an oral selective P2X3 receptor antagonist, is intended for the treatment of refractory chronic cough (RCC) in adults or unexplained chronic cough (UCC).

The drug was approved in Japan and the European Union in January 2022 and September of the same year, respectively (marketed as Lyfnua). However, Gefapixant has now been rejected by the FDA in the United States for the second time.

Merck New Drug for Chronic Cough, Gefapixant Faces Second FDA Rejection

On December 20, Merck announced that the U.S. Food and Drug Administration (FDA) had issued a complete response letter (CRL) regarding its Gefapixant New Drug Application (NDA). This setback follows the FDA’s rejection of Gefapixant in January of the previous year.

In November, an FDA advisory committee voted 12 to 1 against approving Gefapixant by the December 27 PDUFA date.

In the CRL, the FDA concluded that Merck’s application lacked substantial evidence of the effectiveness in treating RCC and UCC. The CRL did not raise concerns about the safety of Gefapixant.

Merck had submitted the NDA in the U.S., including two placebo-controlled trials named P030 and P027. However, Gefapixant did not demonstrate a reduction in cough frequency in the studies. Although Gefapixant was generally safe, taste disturbances or loss were reported in up to 65% of subjects receiving 45mg, leading to treatment discontinuation in 14% of patients.

Currently, the FDA has not approved any therapy for chronic cough, indicating a lack of regulatory precedent for this indication.

Merck stated that they are reviewing the FDA’s feedback to determine the next steps.

While the FDA’s rejection provides insights into how Merck should design studies to meet the agency’s data requirements, conducting another trial would mean investing more time and resources in Gefapixant. The delay in Gefapixant’s approval is eroding Merck’s leading position in this field.

In April of this year, GlaxoSmithKline spent $2 billion to acquire Bellus Health and its P2X3 antagonist, Camlipixant, which is expected to complete phase 3 trials by September 2024 and July 2025. If successful, GlaxoSmithKline could potentially surpass Merck and capture the untapped U.S. market.

It’s worth noting that in February 2022, Bayer’s similar drug, Eliapixant (BAY 1817080), halted development in phase 2 clinical trials due to “overall benefits not exceeding risks.”