Gefapixant gives a taste of what may work for unexplained chronic cough


By Michael Woodhead

4 Mar 2020

A novel drug may help relieve unexplained chronic cough – but at the expense of taste disorders, according to a study in The Lancet Respiratory Medicine.

Results from a phase 2b randomised controlled trial found that gefapixant, a P2X3 receptor antagonist, reduced cough frequency by up to 37% compared to placebo in patients with a one year history of refractory or unexplained chronic cough.

The 12-week trial involving 253 patients also showed that the drug had dose-related adverse effects on taste (dysgeusia) that affected half of people using the highest dose tested and led to discontinuation by 16% of patients.

The study conducted in centres in the US and UK, explored the effects of three doses of the drug that targets the purinergic receptor P2X3 thought to mediate hyperexcitability of sensory neural function that causes cough hypersensitivity syndrome.

Cough frequency was reduced with all the doses tested but only the highest dose of gefapixant (50mg) reduced cough frequency more than placebo. At 12 weeks, patients’ geometric mean awake cough frequency was 18·2 coughs per hour with placebo, 14·5 coughs per hour with 7·5 mg, 12·0 coughs per hour with 20 mg, and 11·3 coughs per hour with 50 mg gefapixant.

These corresponded to percentage reductions in cough of −22·0%, −22·2% and −37·0% with the 7.5mg, 20mg and 50mg doses respectively.

Dysgeusia occurred in three (5%) patients given placebo, six (10%) given 7·5 mg gefapixant, 21 (33%) given 20 mg gefapixant, and 30 (48%) given 50 mg gefapixant.

The study authors said that when followed up two weeks after stopping the drug the patients maintained reduced cough frequency and there was no evidence of a rebound effect.

Gefapixant showed promise as a novel therapy for chronic cough, and phase 3 studies to investigate longer-term antitussive benefit are underway, they added.

An accompanying commentary said an effective treatment for unexplained chronic cough would be welcome as an alternative to the current ‘off label’ trials of neuromodulator approaches with drugs such as gabapentin, pregabalin, amitriptyline and morphine.

But it was important for clinicians to avoid the common pitfalls in labelling chronic cough as unexplained without investigating the contributions of other conditions such as asthma, gastro-oesophageal reflux and rhinosinus conditions, they warned.

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