GSK will discontinue camlipixant for refractory chronic cough after mixed Phase III CALM trial results. CALM-1 met its endpoint, while CALM-2 failed.
Written By: Anamika Koshti, PharmD
Reviewed By: Pharmacally Editorial Team
On July 17, 2026, GSK plc announced results from its Phase III CALM clinical programme evaluating camlipixant, a selective P2X3 receptor antagonist, in adults with refractory chronic cough (RCC). While the CALM-1 study met its primary endpoint, the companion CALM-2 trial did not achieve statistical significance for the same endpoint. Based on the aggregate findings from both studies, GSK concluded that the overall efficacy observed is unlikely to transform patient care and has decided not to advance camlipixant further for RCC. The company plans to present and publish the full dataset to support future research in this disease area.
What Is Refractory Chronic Cough?
Refractory chronic cough is a complex, under-recognised condition in which persistent coughing continues despite appropriate treatment of identifiable underlying causes. The disease can substantially impair quality of life, affecting sleep, work, and daily activities, while treatment options remain limited.
How Camlipixant Works
Camlipixant (BLU-5937) is a selective P2X3 receptor antagonist designed to reduce cough hypersensitivity. P2X3 receptors are ATP-gated ion channels located on sensory nerves within the airways and are believed to contribute to the exaggerated cough reflex seen in RCC. By selectively blocking P2X3 homotrimeric receptors while largely sparing P2X2/3 heterotrimeric receptors, camlipixant was designed to minimise the taste disturbances observed with earlier P2X3 antagonists.
CALM-1 and CALM-2 Trial Design
CALM-1 (NCT05599191) and CALM-2 (NCT05600777) were Phase III, randomised, double-blind, placebo-controlled studies evaluating camlipixant 25 mg and 50 mg, each administered twice daily, in adults with RCC. CALM-1 assessed the primary endpoint at Week 12, whereas CALM-2 evaluated the same endpoint at Week 24. The primary objective in both studies was reduction in 24-hour cough frequency compared with placebo. Key secondary endpoints included patient-reported outcomes measured using the Chronic Cough Diary (CCD).
Phase III Results
CALM-1 met its primary endpoint, with camlipixant 50 mg twice daily demonstrating a statistically significant reduction in 24-hour cough frequency versus placebo at Week 12. However, CALM-2 did not achieve statistical significance for the same primary endpoint at Week 24. The 25 mg twice-daily dose failed to reach statistical significance in either trial. In addition, key secondary endpoints, including CCD outcomes, did not meet predefined target thresholds in either study.
Across both trials, the incidence and severity of treatment-related adverse events were comparable between the camlipixant and placebo groups, indicating a safety profile broadly similar to placebo.
GSK Discontinues Development in RCC
Following review of the combined Phase III data, GSK determined that the overall efficacy demonstrated across the CALM programme was unlikely to meaningfully transform patient care in RCC and has decided not to continue developing camlipixant for this indication. The company also confirmed that results from the CALM programme will be submitted for future scientific presentation and publication to contribute to the understanding of refractory chronic cough.
Development of camlipixant in other indications remains unchanged. The ongoing Phase IIb BALANCE trial (NCT07519395) continues to investigate the drug in adults with irritable bowel syndrome with diarrhoea (IBS-D) and irritable bowel syndrome with mixed bowel habits (IBS-M).
What the Results Mean
The outcome of the CALM programme represents a setback for patients with refractory chronic cough, a condition for which effective treatment options remain limited. Camlipixant’s selective P2X3 inhibition had generated interest because of its potential to reduce cough hypersensitivity while limiting taste-related adverse effects associated with earlier agents in the class. Although the programme did not demonstrate sufficient overall efficacy to support further development in RCC, publication of the complete Phase III findings may provide valuable insights into the role of P2X3 receptor antagonism and help guide future therapeutic research for chronic cough.
Reference
About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.