Source – Merck
MSD has announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of gefapixant. This drug is an investigational, non-narcotic, oral selective P2X3 receptor antagonist developed to treat adults with refractory or unexplained chronic cough. The CHMP’s recommendation will now undergo review by the European Commission (EC) for marketing authorization within the European Union (EU), with a final decision expected later this year.
“Today’s positive CHMP opinion is the next step for gefapixant to become the first treatment approved in the European Union for adults with refractory or unexplained chronic cough,” said Dr. Joerg Koglin, senior vice president, global clinical development, Merck Research Laboratories. Refractory or unexplained chronic cough as a condition with often disruptive, uncontrolled coughing associated with major physical, social and emotional consequences represents a large unmet clinical need.”
– Dr. Joerg Koglin, senior vice president, global clinical development, Merck Research Laboratories
The CHMP’s positive opinion is based on the results from the COUGH-1 and COUGH-2 clinical trials, which represent the first companion Phase III studies conducted in patients with refractory or unexplained chronic cough. This type of cough persists despite appropriate treatment of underlying conditions or when the cause cannot be identified even after a thorough evaluation. Both COUGH-1 and COUGH-2 trials met their primary endpoint by demonstrating a significant reduction in 24-hour cough frequency in adults treated with gefapixant 45 mg twice daily compared to those on placebo at 12 weeks (COUGH-1) and 24 weeks (COUGH-2).
COUGH-1 and COUGH-2 were multinational, randomized, double-blind, placebo-controlled Phase III studies that evaluated the efficacy and safety of gefapixant in reducing cough frequency in adult participants with refractory chronic cough or unexplained chronic cough. A total of 2,044 participants were involved in these trials. Patients were randomly assigned to receive gefapixant 45 mg twice daily, gefapixant 15 mg twice daily, or placebo. The primary efficacy outcomes were 24-hour cough frequency at week 12 for COUGH-1 and 24-hour cough frequency at week 24 for COUGH-2, measured using an ambulatory digital audio recording device. Secondary endpoints included awake cough frequency and the percentage of participants with a significant increase in the Leicester Cough Questionnaire (LCQ) total score from baseline. COUGH-1 had a 12-week treatment period and a 40-week safety-extension period, while COUGH-2 had a 24-week treatment period and a 28-week safety-extension period.
The results showed that adults treated with gefapixant 45 mg twice daily had a statistically significant reduction in 24-hour cough frequency compared to placebo, both at 12 weeks (COUGH-1) and 24 weeks (COUGH-2). However, the treatment arms receiving gefapixant 15 mg twice daily did not meet the primary efficacy endpoint in either Phase III study. The results of these Phase III studies were published in The Lancet.
In 2022, Merck conducted additional analyses to address questions raised by regulatory authorities, primarily related to the cough counting system used to generate the Phase III data, which formed the basis for gefapixant’s marketing authorization application. The results of these additional analyses were generally consistent with the published Phase III results from COUGH-1 and COUGH-2.
