Results were announced from 2 pivotal phase 3 trials evaluating the efficacy and safety of gefapixant (MK-7264; Merck) for the treatment of refractory or unexplained chronic cough.
Gefapixant is an orally administered, selective P2X3 receptor antagonist. It is believed that excessive activation of P2X3 receptors is associated with neuronal hypersensitization in the airways and lungs leading to chronic cough.
The double-blind, placebo-controlled studies, COUGH-1 and COUGH-2, included 730 and 1314 adult patients with refractory or unexplained chronic cough for at least 1 year, respectively. Both studies randomized patients to 1 of 3 cohorts: gefapixant 45mg or 15mg twice daily, or placebo. The primary efficacy end point was 24-hour cough frequency at week 12 (COUGH-1) and week 24 (COUGH-2), measured using an ambulatory audio recording device. Secondary end points included awake coughs per hour and the proportion of patients with greater than 1.3-point increase from baseline in the Leicester Cough Questionnaire (LCQ) total score.
Results from COUGH-1 and COUGH-2 showed that gefapixant 45mg twice daily was associated with an estimated relative reduction in 24-hour cough frequency of 18.45% (95% CI: -32.92, -0.86; P =.041) and 14.64% (95% CI: -26.07, -1.43; P =.031), respectively, compared with placebo. The gefapixant 15mg twice daily arm did not meet the primary end point in either study.
Additionally, a statistically significant reduction in awake coughs per hour (15.79% estimated relative reduction; 95% CI: -27.27, -2.50; P =.022) was observed in COUGH-2 among those treated with gefapixant 45mg twice daily. Patients in the gefapixant 45mg arm also reported a clinically important improvement in cough-related quality of life, with an odds ratio of 1.41 (P =.042) compared with placebo.
As for safety, discontinuation due to adverse events was more frequent in the 45mg arm (15% in COUGH-1 and 20% in COUGH-2) compared with the 15mg (3% and 8%, respectively) or placebo (3% and 5%, respectively) arms. Patients treated with gefapixant 45mg also reported a higher incidence of taste-related adverse events (58% in COUGH-1 and 68.6% in COUGH-2) vs the 15mg (10.7% and 19.5%, respectively) and placebo (3.3% and 8.3%, respectively) arms.
Commenting on the results, Dr Lorcan McGarvey, Clinical Professor, Wellcome-Wolfson Institute of Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, said: “Given the significant unmet need for these patients, we are strongly encouraged by the findings of COUGH-1 and COUGH-2 and the potential for a new therapeutic option for patients who are struggling with the burden of this disease, often for many years without relief.”
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Merck’s gefapixant (45mg twice daily) significantly decreased cough frequency compared to placebo at week 12 and 24 in patients with refractory or unexplained chronic cough. https://www.businesswire.com/news/home/20200908005244/en/. Accessed September 9, 2020.