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 trial
In two Phase III studies, gefapixant 45mg BD reduced 24-hour cough frequency versus placebo in adults with refractory chronic cough (18.5% [95% CI 32.9–0.9]; p=0.041 at week 12) or unexplained chronic cough (14.6% [26.1–1.4]; p=0.031 at week 24) with an acceptable safety profile.
Source:
The Lancet
SPS commentary:
A related Comment notes that the recent greater awareness of the underlying pathobiology of chronic cough has shed light on a new range of treatment targets, including purinergic receptors. P2X3 purinergic receptors are found on sensory nerve fibres in the airway lining and respond to ATP that is released in response to airway inflammation, irritation, and mechanical stress or injury. Several P2X3 receptor antagonists are under development.
They note that the substantial reduction in cough frequency observed in these Phase III trials was attenuated by a large placebo effect (common in cough studies), leading to a diminished relative reduction that just reached statistical significance. The main adverse effects included taste-related adverse events (59.3% in COUGH-1 and 68.9% in COUGH-2) and 16.9% and 20%, respectively, discontinued treatment due to side-effects in the 45mg BD arm. They comment that a ‘clear trade-off exists between efficacy (cough suppression) and safety (side-effects) and further investigation of patient priorities should be considered.’