P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study

In this small Phase II study, a first-in-class oral P2X3 antagonist reduced daytime cough frequency at 2 weeks versus placebo in patients with refractory chronic cough. Taste disturbances were reported by all patients taking active treatment and led to some withdrawals.

According to an accompanying comment article, preclinical studies suggest that P2X3 receptors are expressed by airway vagal afferent nerves and contribute to the hypersensitisation of sensory neurons. P2X3 antagonists have therefore been proposed as a possible treatment and AF-219 is the first-in-class. The mechanisms for the inhibitory activity of AF-219 observed in this study are not known, and whether AF-219 could be effective in chronic cough secondary to other disorders remains an open question.

The authors have suggested that the adverse effect of taste disturbance might be avoided at lower doses; further information from dose ranging and long-term safety and efficacy studies is required to address this.