P2X3 receptor antagonists pass Phase 3 trials for cough – potential also in pain?

P2X3 receptor channels are attractive therapeutic targets as they are expressed in sensory neurons, activated by extracellular ATP and serve important roles sensory hypersensitization including pain.

Merck has been leading the field in this area after they gained gefapixant, also known as MK-7264, in the 2016 takeover of Afferent Pharmaceuticals, with a therapeutic focus on chronic cough.

Just this week (WB 16th March 2020) there have been a number of significant advancements announced.

Positive Phase III data from Merck

Merck has publicised that gefapixant produced statistically significant improvements in chronic cough patients in two phase III trials. Across the two trials, Merck enrolled around 2,000 patients and randomized them to receive one of two doses of gefapixant or placebo. One trial looked at the average hourly number of coughs after 12 weeks of treatment, while the other, larger study performed the same assessment after 24 weeks. The efficacy is seen at the top dose of the compound which is also asscoaited with taste-related events, which led to some discontinuations.

Merck press release: https://www.businesswire.com/news/home/20200317005183/en/Merck-Announces-Top-Line-Results-Phase-3-Trials

Although no actual data is released for the phase III studies the Phase IIb data for Gefapixant were recently published in the Lancet.

Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial

Prof Jaclyn A Smith et al., https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30471-0/fulltext

Bellus Health complete Phase II

At the same time BELLUS Health announces completion of enrolment in Phase 2 RELIEF Trial of its P2X3 antagonist BLU-5937 for the treatment of refractory chronic cough.

Details from press release: https://finance.yahoo.com/news/bellus-health-announces-completion-enrollment-110000216.html

Good news for pain patients too…

This could be good news for pain patients too. There is much preclinical data to suggested a significant role for P2X3 mediating pain in hypersensitivity disorders and the company Nocion was recently established working on cough mechanisms to provide a new way to find pain medicines.

https://www.statnews.com/2019/04/17/how-one-company-thinks-unraveling-cough-can-provide-a-new-way-to-treat-pain/

However, it should be noted though that chronic cough doesn’t seem to be a more efficient clinical path to approach compared to pain, as Merck enrolled around 2000 patients in their phase III clinical trials alone, which is similar or even more than one would need for pain drug development.