After years of research into how to treat patients with unexplained or refractory chronic cough, it seemed that companies and scientists were close to an answer with P2X3 antagonists. GSK, Merck and Bayer were advancing drug candidates belonging to the same class, as P2X3 is a validated biological target implicated in cough reflex hypersensitization.
But a new setback from GSK has deepened doubts over the class following Bayer's discontinuation and a complete response letter for Merck's candidate. The question now is what's next for patients who have long been shunted to the sidelines.
'Unlikely To Transform Patient Care'
GSK said on July 17 that it would stop testing camlipixant, the refractory chronic cough drug it acquired with Bellus Health for $2bn in 2023, for the indication after reporting mixed Phase III data.
The P2X3 receptor antagonist, once deemed a potential blockbuster by analysts, met the primary endpoint of the CALM-1 trial, showing statistically significant reductions in 24-hour cough frequency after 12 weeks versus placebo at a 50mg dose.
However, the drug failed the same endpoint in the CALM-2 study at week 24 and did not meet secondary endpoints in either study. A lower 25mg dose did not reach statistical significance for the primary endpoint in either study.
"Based on the aggregate data, the limited efficacy demonstrated is unlikely to transform patient care," GSK said. The company will drop the drug's development in refractory chronic cough but will continue testing it in the Phase IIb BALANCE trial for irritable bowel syndrome, it added.