Merck Announces Positive Top-Line Results from Two Phase III Studies of Gefapixant in Refractory or Unexplained Chronic Cough

On March 17, Merck Sharp & Dohme (MSD) announced the primary results from two pivotal Phase III studies, COUGH-1 and COUGH-2, evaluating gefapixant (MK-7264) for the treatment of refractory or unexplained chronic cough. The Week 12 results from COUGH-1 and the Week 24 results from COUGH-2 demonstrated that gefapixant 45 mg twice daily significantly reduced hourly cough frequency compared with placebo; however, gefapixant 15 mg twice daily failed to meet the primary efficacy endpoint of reducing cough frequency in either study. The efficacy and safety profile of gefapixant was consistent with findings from Phase II studies. Both trials will continue to collect additional evidence.

The COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) studies both adopted an international, multicenter, randomized, double-blind, placebo-controlled design. They enrolled 732 and 1,317 patients, respectively, with refractory or unexplained chronic cough lasting more than one year. Both studies randomly assigned participants into three groups: gefapixant 45 mg, gefapixant 15 mg, and placebo. The primary efficacy endpoints were the mean number of coughs per hour over 24 hours at Week 12 and Week 24, respectively.

The global prevalence of chronic cough (defined as a cough lasting more than 8 weeks) in adults is approximately 10%. Currently, no new drugs have been approved for the treatment of chronic cough. Gefapixant is an oral selective P2X3 receptor antagonist. Overactivation of P2X3 receptors is considered to be associated with sensory neuron hypersensitivity. Sensory neuron hypersensitivity occurs following injury or infection of the airways and lungs, leading to persistent and frequent coughing.