Merck’s chronic cough drug gefapixant clears phase 3 test

Merck & Co/MSD’s experimental drug gefapixant has improved the frequency of coughing in a pair of phase 3 trials, potentially setting up regulatory filings this year.

At the moment there are no approved therapies for suppressing chronic cough – defined as lasting for eight weeks or more – and oral P2X3 purinergic receptor inhibitor gefapixant is at the head of a pack of new drugs vying to bring that situation to an end.

It has been estimated that chronic cough affects up to 10% of the US population, with one in five of them getting no benefit from current treatments such as opioids and corticosteroids.

Merck has previously said it thinks gefapixant is one of the top prospects in its pipeline as it tries to reduce its reliance on $11 billion cancer blockbuster Keytruda (pembrolizumab).

The two trials (COUGH 1 and 2) involved around 2,000 people with chronic cough due to unknown causes who were treated with one of two doses of gefapixant or placebo.

At the higher 45mg dose the drug met its primary objective of a statistically significant decrease in coughs per hour over 24 hours compared to placebo. The lower 15mg dose didn’t meet that endpoint.

The data keeps Merck in the lead among P2X3 antagonist developers, a group that also includes Bellus Health, whose BLU-5937 candidate is in phase 2 with results due in mid-2020, as well as Bayer. Shares in Bellus rose almost 11% after Merck released the op-line data.

P2X3 receptors are found on sensory nerve cells and appear to get more numerous after nerve injury or inflammation, with a number of pathological consequences. They are thought to become over-activated in chronic cough, playing a role in the hyper-sensitisation of neurons in airways that trigger the cough reflex. Other potential indications include endometriosis and chronic pain.

One potential weakness for Merck’s drug is that it seems to have an effect on taste sensation at higher doses, so the failure of the lower 15mg dose in COUGH 1 and 2 is a disappointment.

That could provide an opportunity for rivals like BLU-5937, unless the change in taste is found to be a class effect. So far, Bellus says it hasn’t seen an impact on taste with its drug.

Merck added gefapixant to its stable in 2016 when it bought Afferent Pharma in a $1.25 billion deal, including $500 million upfront and $750 million in development and commercial milestones. Afferent picked up the P2X3 programme from Roche more than a decade ago.