There are no FDA-approved treatments for recurrent chronic cough, and a GSK drug from a $2 billion acquisition just lost its chance to become the first one.
The drug, camplipixant, was developed specifically for refractory chronic cough (RCC), defined as cough that lasts for more than eight weeks and does not respond to treatment. GSK has mixed results from two placebo-controlled Phase 3 tests, each testing a high dose and a low dose of the twice-daily pill.
GSK’s Friday announcement did not provide specific figures for the trial readouts. In one test, GSK said results show the high dose met the main goal of showing statistically significant reduction in cough frequency measured at week 12. But in the second study, the high dose did not reach the same endpoint measured at week 24. The low dose of camplipixant did not achieve statistically significant results in either study. GSK also said that on key secondary goals, the drug did not meet target thresholds in either study.
“Based on the aggregate data, the limited efficacy demonstrated is unlikely to transform patient care,” the company said in its announcement. “GSK has decided not to progress further development of camlipixant in RCC.”
Camlipixant is an oral small molecule designed to block P2X3, a receptor that’s associated with the cough mechanism. The drug was initially developed by Bellus Health. In 2023, GSK paid $2 billion to buy Laval, Quebec-based Bellus. At the time of the deal, camlipixant had already started both Phase 3 studies.
Blocking P2X3 has some validation from gefapixant, brand name Lyfnua. This Merck drug has approvals in Europe and Japan for chronic cough, though it has fallen short at the FDA. In clinical testing, one of the more common side effects reported for this Merck drug was a persistent unpleasant taste in the mouth. Camlipixant was designed to be more selective to P2X3 to reduce this side effect. GSK said nothing about patient reports of foul taste, but the drug’s failure to achieve statistically significant cough reduction makes that measure moot.
GSK did say that across both Phase 3 trials, results showed the adverse event profile was similar across the camlipixant and placebo arms. That’s important because GSK is still testing P2X3 inhibition as a way to treat irritable bowel syndrome (IBS) with diarrhea and irritable bowel syndrome mixed, in which the disease cycles between constipation and diarrhea. This Phase 2b test of camlipixant in IBS is ongoing.
Camlipixant’s failure leaves removes a competitor to Trevi Therapeutics, which is developing a reformulated opioid for two types of cough. The Trevi drug, Haduvio, is based on nalbuphine, a drug that targets kappa- and mu-opioid receptors that play a role in the cough mechanism. This decades-old opioid is typically administered as in injection or infusion. Haduvio is an oral extended-release formulation of nalbuphine.
Trevi is preparing for Phase 3 testing of Haduvio in chronic cough in idiopathic pulmonary fibrosis. A mid-stage study is ongoing in refractory chronic cough. Leerink Partners analyst Roanna Ruiz, who follows Trevi, said in a research note that termination GSK’s drug in chronic cough clears the way for Haduvio. She added that the GSK drug’s results underscore the challenges for addressing a peripheral mechanism of cough, such as P2X3 antagonism, versus the centrally acting approach of Trevi’s drug.
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