Efficacy and Safety of Gefapixant for Refractory/Unexplained Chronic Cough

In phase 3 randomized clinical trials, gefapixant 45 mg twice daily was efficacious and had an acceptable safety profile over 52 weeks of treatment for refractory or unexplained chronic cough, according to a poster presentation for the CHEST 2021 Annual Meeting, held virtually October 17 to 20.

The investigators presented results from a pooled analysis of COUGH-1 and COUGH-2 (ClinicalTrials.gov Identifiers: NCT03449134 and NCT03449147, respectively).

COUGH-1 and COUGH-2 were randomized, double-blind, placebo-controlled studies that evaluated the efficacy of the P2X3 receptor antagonist gefapixant in reducing cough frequency in adult participants with refractory or unexplained chronic cough. Participants were randomized to receive placebo, gefapixant 15 mg twice daily, or gefapixant 45 mg twice daily for 52 weeks.

The primary endpoints for COUGH-1 and COUGH-2 were 24-hour cough frequency at 12 weeks and 24-hour cough frequency at 24 weeks, respectively. Secondary endpoints in both trials included several patient-reported outcomes measured using validated tools: the Leicester Cough Questionnaire (LCQ), the visual analog scale (VAS) for cough severity, and the Cough Severity Diary (CSD). Efficacy was evaluated through 52 weeks total. Adverse events (AEs) were monitored throughout the studies.

The investigators used logistic regression models to evaluate the change from baseline for the responders. Outcomes investigated included: an LCQ total score increase of at least 1.3 points; at least 30 mm reduction in mean weekly cough severity VAS score; and a reduction of at least 1.3 points and a reduction of at least 2.7 points in mean weekly CSD total score.

The pooled dataset included a total of 2044 participants. Odds ratios (OR) favored either dose of gefapixant over placebo for each responder endpoint. Outcomes for gefapixant 45 mg twice daily were as follows: for the LCQ, the OR (95% confidence interval) was 1.42 (1.11–1.83) at 12 weeks, 1.37 (1.06–1.77) at 24 weeks, and 1.72 (1.31–2.27) at 52 weeks; for the cough severity VAS, the OR (95% CI) was 1.53 (1.21–1.93) at 12 weeks, 1.70 (1.34–2.16) at 24 weeks, and 1.47 (1.15–1.89) at 52 weeks; for the CSD (≥1.3), the OR (95% CI) was 1.33 (1.05–1.67) at 12 weeks, 1.47 (1.14–1.90) at 24 weeks, and 1.62 (1.23–2.15) at 52 weeks; and for CSD (≥2.7), the OR (95% CI) was 1.49 (1.18–1.89) at 12 weeks, 1.70 (1.33–2.16) at 24 weeks, and 1.57 (1.21–2.03) at 52 weeks.

Adverse events related to taste were the most common AEs, and taste-related AEs contributed to dose-related treatment discontinuation rates. Among participants who received gefapixant 45 mg twice daily, 14% discontinued due to taste-related AEs. Serious AEs occurred at similar rates (both 6%) in the placebo and gefapixant 45 mg twice daily groups.

“Gefapixant 45 mg [twice daily] resulted in efficacy over 52 weeks of treatment as assessed by several validated [patient-reported outcome] measures,” concluded the authors. “These results provide meaningful patient-relevant evidence in support of the long-term efficacy of gefapixant 45mg [twice daily] for the treatment of patients with chronic cough.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Dicpinigaitis P, Birring S, Morice A, et al. Treatment of refractory or unexplained chronic cough with gefapixant, a P2X3 receptor antagonist, over 52 weeks in two phase III clinical trials. Presented at: CHEST 2021; October 17-20, 2021; Orlando, FL/Virtual. Abstract A2361-A2362.