Gefapixant Associated With Clinically Meaningful Reduction in Chronic Cough Frequency

Twice daily gefapixant 45 mg was associated with a clinically meaningful reduction in cough frequency in patients with chronic cough that is either unexplained or refractory to another condition, according to findings presented at the American Thoracic Society (ATS) 2021 International Conference, held virtually from May 14 to May 19, 2021.

Using the results of 2 large, phase 3 clinical trials — COUGH-1 and COUGH-2 — researchers presented a pooled analysis of objective cough frequency following treatment with gefapixant, a P2X3 receptor antagonist associated with significant reduction in 24-hour cough frequency.

The 2 companion studies (ClinicalTrials.gov Identifiers: NCT03449134 and NCT03449147), included participants aged 18 years and older with 1 year or more of chronic cough, a diagnosis of chronic cough refractory to treatment for associated conditions (RCC) or chronic cough unexplained with no associated condition (UCC), and a baseline cough severity Visual Analogue Scale (VAS) score or 40 mm or more. Participants were randomly assigned to receive either placebo, gefapixant 15 mg twice daily, or gefapixant 45 mg twice daily.

The VitaloJAK™ (Vitalograph Inc) ambulatory recording device was used to record cough frequency; data were analyzed via both software and human analysts. Objective cough frequency endpoints included both 24-hour cough frequency and Awake Cough Frequency (coughs per hour during waking hours).

The total cohort included 2044 patients with RCC or UCC across both trials. The estimated relative reductions for gefapixant 45 mg vs placebo were 18.59% and 17.38% for 24-hour cough and awake cough frequencies, respectively. For gefapixant 15 mg, estimated relative reductions were 0.97% and -0.28%, respectively.

Compared with placebo, gefapixant 45 mg was not associated with serious adverse events. Taste-related adverse events were reported.  

“The pooled analysis of COUGH-1 and COUGH-2 is the largest prospective analysis of clinical trial data in chronic cough to date,” the researchers concluded. “Gefapixant 45 mg provided clinically important reduction in cough frequency vs placebo and was not associated with an increase in serious adverse events.”

Reference

Smith J, Morice AH, McGarvey L, et al. Objective cough frequency with gefapixant in chronic cough: a pooled analysis of two phase 3 randomized, controlled clinical trials (COUGH-1 and COUGH-2). Presented at: the American Thoracic Society (ATS) 2021 International Conference; May 14-19, 2021. Abstract A2353.