Merck's Lyfnua (Gefapixant) Approved in Japan as the World’s First Selective P2X3 Receptor Antagonist for Refractory and Unexplained Chronic Cough

Chronic cough (Image source: quickanddirtytips.com）

News on January 24, 2022 /BioValleyBIOON/ -- Recently, MSD's (Merck & Co.) new cough medicine Lyfnua (gefapixant, MK-7264) 45mg tablets have been approved in Japan: This drug is aAn oral, selective P2X3 receptor antagonist for the treatment of refractory chronic cough (RCC) or unexplained chronic cough (UCC) in adults.. At present, Lyfnua is also being accepted in the United StatesFDAThe review, used for adult treatment of RCC or UCC.

RCC refers to a cough that persists despite appropriate treatment for the underlying disease, and UCC refers to a cough for which no underlying cause can be identified despite comprehensive evaluation. In terms of medication, Lyfnua 45mg tablets are taken twice daily.

It is worth mentioning that,Lyfnua is the world's first approved selective P2X3 receptor antagonist and the first drug specifically for the treatment of RCC and UCC. Lyfnua inhibits extracellular ATP signaling by targeting P2X3 receptors located on vagal C-fibers in the airways, reducing sensory nerve activation and cough.

It is estimated that 5%-10% of adults worldwide suffer from chronic cough. A subset of these patients have refractory chronic cough (RCC) and unexplained chronic cough (UCC), which are more sensitive to various triggers that normally do not cause coughing in healthy individuals. This includes daily activities (such as talking and laughing), temperature changes, exposure to aerosols, or food odors. To date, treatment options for these patients are extremely limited, and many have often gone years without relief.

The approval and market launch of Lyfnua will bring an innovative treatment option to the patient population struggling with the burden of this disease. According to the exclusive distribution agreement signed with MSD, in Japan, Lyfnua will be exclusively distributed by KYORIN Pharmaceutical, a subsidiary of KYORIN Holdings.

Gefapixant Chemical Structure (Source: medchemexpress.com)

The efficacy and safety of gefapixant in two pivotal Phase 3Clinical Trial(COUGH-1, COUGH-2) have been confirmed. COUGH-1 and COUGH-2 are the first-ever parallel Phase 3 trials conducted in adult patients with RCC and UCC. Data from these two trials were presented at the virtual European Respiratory Society (ERS) International Congress held in September 2020.

The results showed that the study met the primary endpoint:Compared with the placebo group, the gefapixant 45mg twice-daily treatment group showed a statistically significant reduction in 24-hour cough frequency (objectively measured by 24-hour audio recording to count coughs per hour) at Week 12 (COUGH-1 study) and Week 24 (COUGH-2 study).Notably, in two studies, the treatment group receiving 15 mg of gefapixant twice daily did not meet the primary efficacy endpoint.

The specific data are as follows: (1) In the COUGH-1 study, at week 12 of treatment, the 24-hour cough frequency in the group treated with gefapixant at a dose of 45 mg twice daily was significantly reduced by 18.45% (95% CI: -32.92 to -0.86; p=0.041) compared to the placebo group; (2) In the COUGH-2 study, at week 24 of treatment, the 24-hour cough frequency in the group treated with gefapixant at a dose of 45 mg twice daily was significantly reduced by 14.64% (95% CI: -26.07 to -1.43; p=0.031) compared to the placebo group. On average, patients taking gefapixant at a dose of 45 mg twice daily experienced a 62% reduction in cough frequency from baseline in the COUGH-1 trial and a 63% reduction in cough frequency from baseline in the COUGH-2 trial.

The secondary endpoints supported the primary observations of the study. The results for early morning cough frequency were generally similar to those for 24-hour cough frequency. The twice-daily 45mg dose group achieved statistical significance in the COUGH-2 study (estimated relative reduction of 15.79%, 95% CI: -27.27 to -2.50; p=0.022) and showed a trend towards significance in the COUGH-1 study (estimated relative reduction of 17.68%, 95% CI: -32.5 to 0.50; p=0.056). At week 24, the twice-daily 45mg dose group demonstrated a significant improvement in cough-related quality of life compared to the placebo group (HR=1.41, p=0.042). Among patients in the 45mg dose group, 77.1% experienced clinically meaningful improvements in cough-related quality of life (as measured by LCQ).

In two studies, the safety and tolerability of gefapixant were consistent with previous research reports. The incidence of serious adverse events was similar across groups (<4%). The 45mg group had a higher frequency of discontinuation due to adverse events and a higher incidence of taste-related adverse events. Most taste-related adverse events were mild to moderate. (Bioon.com)