Gefapixant significantly reduces Refractory Chronic cough frequency: Study

The results have been put forth in the Virtual European Respiratory Society (ERS) International Congress 2020.

Effective treatments for cough are a significant unmet clinical need, with no new therapies approved in >50 years. Chronic refractory cough (CRC) is defined as a cough that persists despite guideline-based treatment. It is seen in 20-46% of patients presenting to specialist cough clinics and it has a substantial impact on the quality of life and healthcare utilization.

Gefapixant is an investigational, orally-administered, selective P2X3 receptor antagonist, for the potential treatment of refractory or unexplained chronic cough.

Though a recent study evaluating gefapixant (MK-7264; formerly known as AF-219) in refractory chronic cough patients, revealed a 75% reduction in daytime cough frequency compared to placebo, accompanied by striking improvements in patient-reported outcomes, due to usage of a very high single dose of the drug, all patients had reported altered taste acuity.

Therefore, the current investigation by Jaclyn A Smith and the team, from the University of Manchester and Manchester Academic Health Science Centre, UK, explored the efficacy and tolerability of gefapixant for the treatment of chronic cough using a dose-escalation approach.

COUGH-1 and COUGH-2 are the first companion Phase 3 trials ever conducted in patients with refractory chronic cough, a cough that persists despite appropriate treatment of underlying conditions, or unexplained chronic cough, a cough where the underlying cause cannot be identified despite a thorough evaluation.

COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) are international Phase 3, randomized, double-blind, placebo-controlled, studies to evaluate the efficacy and safety of gefapixant in reducing cough frequency in adult participants with refractory or unexplained chronic cough.

A total of 2,044 participants (75% female, mean age 58 years, mean cough duration 11 years) were treated in COUGH-1 (n=730) and COUGH-2 (n=1,314). In both studies, patients were randomized to one of three groups: gefapixant 45 mg twice daily, gefapixant 15 mg twice daily, or placebo. Participants remained on their assigned treatment at randomization throughout both studies. The primary efficacy outcomes measure for COUGH-1 and COUGH-2 were 24-hour cough frequency at Week 12, and 24-hour cough frequency at week 24, respectively, measured using an ambulatory digital audio recording device. Secondary endpoints in both trials included awake coughs per hour and the percentage of participants with a greater than the 1.3-point increase from baseline.

On analysis, the following key facts emerged.

• In clinical studies, gefapixant doses ≥30mg produced maximal improvements in cough frequency compared with placebo (P<0.05); reported cough severity measures improved at similar doses.
• Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150mg.
• P2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated.

"The results of these studies both corroborate and expand upon those reported in the first study of gefapixant, now demonstrating that anti-tussive effects can be achieved at a fraction of the original 600mg BID dose tested. This study both highlights the importance of objective assessments of efficacy in the optimal development of cough therapies and suggest gefapixant shows promise as an efficacious novel therapy." said the team.

Primary source: European Respiratory Society

For the full article follow the link: 10.1183/13993003.01615-2019