Gefapixant and cough

Gefapixant is a P2X3 receptor antagonist that can be used to treat refractory or unexplained chronic cough (1,2,3)

• P2X3 antagonists
  • these agents bind to the P2X3 receptor, an adenosine triphosphate–gated ion channel on chemically sensitive airway C-fibers
  • blocking this receptor prevents adenosine triphosphate from opening the channel, thereby reducing activation of C-fibers that transmit action potentials to the brainstem and somatosensory cortex that control cough
• gefapixant significantly reduced cough frequency in patients with refractory chronic cough or unexplained chronic cough after 12 weeks of treatment compared with placebo (1)
• gefapixant showed efficacy in phase 3 clinical trials for refractory chronic cough or unexplained chronic cough (2)
  • the most common adverse events were related to taste disturbance
• in a dose-response meta-analysis that included 9 randomized clinical trials and 2980 patients, compared with placebo, use of gefapixant (45 mg orally twice daily) reduced cough frequency by 17.6%, decreased cough severity by 6.2 mm on the 100-mm visual analog scale, and improved cough quality of life by 1 point on the Leicester Cough Questionnaire (score range, 3-21) (3)
  • patients treated with gefapixant (45 mg orally twice daily) had a 32% increase in taste-related adverse events compared with placebo

Reference:

1. Smith JA et al; Protocol 012 Investigators. Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Lancet Respir Med. 2020 Aug;8(8):775-785.
2. McGarvey LP et al; COUGH-1 and COUGH-2 Investigators. Efficacy and safety of gefapixant, a P2X₃ receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. Lancet. 2022 Mar 5;399(10328):909-923.
3. Kum E et al. Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough: A Systematic Review and Dose-Response Meta-Analysis. JAMA. 2023 Oct 10;330(14):1359-1369.