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The National Institute for Health and Care Excellence (NICE) has terminated its appraisal of gefapixant (Lyfnua; Merck Sharp & Dohme) for the treatment of refractory or unexplained chronic cough in adults.
On 30 April 2024, NICE announced that the committee was unable to make a recommendation, following confirmation from manufacturer Merck Sharp & Dohme that it does “not intend to make an evidence submission for the appraisal”.
The manufacturer came to the decision owing to “a lack of evidence on healthcare resource use” during diagnosis and treatment of refractory or unexplained chronic cough, NICE said.
Results from two clinical trials, published in The Lancet in March 2022, showed that for patients taking gefapixant — an oral P2X3 receptor antagonist — their frequency of cough reduced by 18.5% and 14.6%, compared to placebo, at 12 and 24 weeks, respectively.
Researchers also found that more than half of participants taking gefapixant experienced taste disturbance side effects, possibly because of its additional affinity for blocking P2X2 receptors, which are located on taste buds.
The Medicines and Healthcare products Regulatory Agency approved gefapixant in December 2023 and it has been available in several countries, including Switzerland and Japan, since 2023.
However, the drug was rejected by the US Food and Drug Administration (FDA) owing to uncertainties around its clinical benefit. The FDA reported that re-analysis of trial data found that gefapixant use differed from placebo by only one to two coughs per hour.
Commenting on the termination of NICE’s appraisal, Darush Attar-Zadeh, clinical fellow respiratory pharmacist at North West London Integrated Care Board, and co-chair of the Taskforce for Lung Health’s Medicines Optimisation Working Group, said: “I’m not surprised of NICE’s termination decision, given that the manufacturer of gefapixant hasn’t provided an evidence submission.
“There are other drugs in the pipeline that work in similar ways that may provide some more of the answers we need in a carefully selected (homegeneous) group of patients,” he added.
“For now, as clinicians it’s important we take a careful stepwise history of the potential causes of a person’s chronic cough, treat/manage where we can (pharmacologically and non-pharmacologically) and identify any potential red flags for referral,” said Attar-Zadeh.
Chronic cough is usually dry or minimally productive, lasts for at least eight weeks (often much longer) and predominantly affects middle-aged females. It is estimated to affect between 5% and 15% of people in the UK.
As of May 2018, almost £500m is spent annually on over-the-counter (OTC) products for cough and cold relief. Despite these figures, several specialists have questioned their effectiveness.
In its announcement, NICE said that further review of gefapixant will be conducted “if the manufacturer decides to make an evidence submission”.
