Gefapixant may relieve chronic cough, but it’s not to everyone’s taste


By Mardi Chapman

8 Mar 2022

Gefapixant is the first treatment to show efficacy with an acceptable safety profile in phase 3 clinical trials for refractory or unexplained chronic cough.

The oral P2X3 receptor antagonist was trialed in two international RCTs which together comprised more than 2,000 patients.

In the COUGH-1 trial, gefapixant 45 mg twice per day reduced the objective 24 hr cough frequency over 12 weeks by 18·5% compared to placebo.

The results, published in The Lancet, were supported by similar findings in the larger COUGH-2 trial which found a relative reduction in 24 ­hr cough frequency over 24 weeks of 14·6% with gefapixant versus placebo.

Cough frequency reduction was evident by week 4 and increased through week 12 for COUGH-1 and week 24 for COUGH-­2.

“Importantly, the clinical relevance of the significant reductions in cough frequency was supported by the patient­-reported key secondary efficacy outcome that showed that gefapixant 45 mg twice per day resulted in a greater proportion of participants achieving a clinically meaningful improvement in cough-­specific quality of life as measured by a 1·3 ­point increase or more in the Leicester Cough Questionnaire,” the researchers said.

Gefapixant at a lower dose of 15 mg twice per day did not lead to a significant reduction in cough frequency versus placebo in either trial.

Taste-­related adverse events especially dysgeusia were the most common adverse events – mostly mild to moderate in intensity and reversed on discontinuation of therapy.

The study concluded that gefapixant 45 mg twice per day was an effective therapeutic option to address the current absence of licensed treatments for refractory and unexplained chronic cough.

An accompanying Comment article in The Lancet said clinicians often relied on off-label treatments including morphine, amitriptyline, gabapentin and pregabalin to manage chronic cough.

Authors Dr Dennis Thomas and Professor Peter Gibson, from the Priority Research Centre for Healthy Lungs at the University of Newcastle, said the side effects of alteration or loss of taste leading to early discontinuation of therapy could limit the drug’s usefulness.

“A clear trade-off exists between efficacy (cough suppression) and safety (side-effects), and further investigation of patients’ priorities should be considered,” they said.

“Developing more selective P2X3 receptor antagonists might provide similar or better antitussive efficacy with fewer side-effects.”

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