GSK setback deepens P2X3 cough drug doubts
GSK has stopped developing camlipixant for refractory chronic cough after mixed Phase 3 results, adding another setback to a P2X3 drug class that has repeatedly struggled to turn biological promise into convincing clinical benefits.
Why it matters: P2X3 antagonists were expected to create a new treatment class for patients whose cough persists despite treating underlying conditions. Instead, programmes from GSK, Bayer and MSD have encountered limited efficacy, safety concerns or regulatory resistance.
How it works: P2X3 receptors sit on sensory nerves in the airways and help transmit signals that trigger coughing. Blocking them can dampen an oversensitive cough reflex, but developers have struggled to achieve a strong effect without interfering with related receptors involved in taste.
Zoom in: The higher 50 mg dose of camlipixant met the primary endpoint in the CALM-1 trial, significantly reducing 24-hour cough frequency compared with placebo after 12 weeks.
Yes, but: The same dose failed to reach statistical significance after 24 weeks in CALM-2. A lower 25 mg dose missed the primary endpoint in both trials, while key secondary measures also fell short.
- GSK said the combined results showed limited efficacy that was unlikely to transform patient care and ended development in chronic cough. A Phase 2b trial testing camlipixant in irritable bowel syndrome will continue.
Backstory: GSK gained camlipixant through its $2 billion (€1.7 billion) acquisition of Canadian biotech Bellus Health in 2023. It had forecast annual peak sales of more than £2.5 billion (€2.9 billion), partly because the drug was designed to avoid the taste disturbances associated with less selective P2X3 inhibitors.
The big picture: Camlipixant is not the first P2X3 programme to disappoint.
- Bayer discontinued eliapixant in 2022 after concluding that its overall benefits no longer outweighed its risks. The Phase 2b cough study had produced an efficacy signal, but a case of drug-induced liver injury contributed to the end of the wider development programme. Eliapixant stemmed from a collaboration between Bayer and fellow German biotech Evotec.
- MSD’s gefapixant reached the market in the EU as Lyfnua, but its benefit was modest and taste disturbances were common. The FDA rejected the drug twice after questioning whether the trials provided substantial evidence of clinically meaningful efficacy.
What’s next: The P2X3 class has not been completely abandoned yet, as China’s Humanwell Healthcare plans to test HW091077 in a Phase 2 trial in refractory or unexplained chronic cough.
The bottom line: P2X3 remains a validated biological target, but the increasingly difficult question is whether blocking it can deliver enough benefit for patients to justify a commercially successful medicine.
