September 25, 2022

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The world first selective P2X3 receptor antagonist significantly reducing cough frequency!



 

The world first selective P2X3 receptor antagonist significantly reducing cough frequency!

Innovative drug for chronic cough! Merck’s Lyfnua (Gefapixant) approved in Japan: Lyfnua (Gefapixant) is the first drug to treat refractory chronic cough (RCC) or unexplained chronic cough (UCC).

 

Recently, Merck & Co’s new cough medicine Lyfnua (Gefapixant, MK-7264) 45mg tablet was approved in Japan: the drug is an oral, selective P2X3 receptor antagonists for the treatment of refractory chronic cough (RCC) or unexplained chronic cough (UCC) in adults . Lyfnua is also currently under review by the U.S. FDA for the treatment of RCC or UCC in adults.

 

RCC refers to cough that persists despite appropriate treatment for the underlying disease, and UCC refers to cough in which the underlying cause cannot be identified despite thorough evaluation. For medication, Lyfnua 45mg tablets are taken twice a day.

 

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 through P2X3 receptors present on airway vagal C fibers and reduces sensory nerve activation and cough.

 

It is estimated that 5%-10% of adults worldwide suffer from chronic cough. A subset of these patients, refractory chronic cough (RCC) and unexplained chronic cough (UCC), are more sensitive to triggers that do not normally cause cough in healthy subjects.

This includes daily activities (such as talking and laughing), temperature changes, exposure to aerosols or food smells. To date, treatment options for these patients have been extremely limited, and many often go years without remission.

 

The approval of Lyfnua will bring an innovative treatment option to patient populations battling the burden of this disease. In Japan, Lyfnua will be exclusively distributed by KYORIN Pharmaceutical, a subsidiary of KYORIN Holdings, under an exclusive distribution agreement with Merck & Co.

The world first selective P2X3 receptor antagonist significantly reducing cough frequency!

Chemical structure of Gefapixant

 

The efficacy and safety of Gefapixant have been demonstrated in 2 pivotal Phase 3 clinical trials (COUGH-1, COUGH-2). COUGH-1 and COUGH-2 are the first-ever parallel Phase 3 trials in adults with RCC and adults with UCC. Data from these two trials were presented at the online European Respiratory Society (ERS) International Congress in September 2020.

 

The results showed that the study met its primary endpoint: 24-hour cough frequency ( There was a statistically significant reduction in the number of coughs per hour objectively measured using 24-hour recordings . Notably, in 2 studies, the 15 mg twice-daily Gefapixant group did not meet the primary efficacy endpoint.

 

The specific data are:

(1) In the COUGH-1 study, in the 12th week of treatment, compared with the placebo group, the 24-hour cough frequency of the 45 mg twice-daily Gefapixant treatment group was significantly reduced by 18.45% (95% CI: -32.92 to -0.86; p=0.041);

(2) In the COUGH-2 study, at week 24 of treatment, the 24-hour cough frequency was significantly reduced by 14.64% (95% CI) in the 45 mg twice-daily Gefapixant group compared with the placebo group : -26.07 to -1.43; p=0.031).

On average, patients taking the 45 mg twice-daily dose of Gefapixant had a 62% reduction in cough frequency compared to baseline in the COUGH-1 trial and a 63% reduction in cough frequency compared with baseline in the COUGH-2 trial.

 

The world first selective P2X3 receptor antagonist significantly reducing cough frequency!

Lyfnua (Gefapixant) pivotal Phase 3 clinical trial (COUGH-1, COUGH-2) results

 

Secondary endpoints supported the primary observation of the study.

The morning cough frequency results were generally similar to the 24-hour cough frequency results, reaching statistical significance in the COUGH-2 study with the 45 mg twice daily dose (estimated relative reduction 15.79%, 95% CI: -27.27 to -2.50; p=0.022) , trended toward 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 45 mg twice daily dose group had a significant improvement in cough-related quality of life compared with the placebo group (HR=1.41, p=0.042).

Among patients in the 45 mg dose group, 77.1% experienced a clinically important improvement in cough-related quality of life (as measured by LCQ).

 

In both studies, the safety and tolerability of Gefapixant was consistent with previous reports. Serious adverse event rates were similar across groups (<4%).

The 45 mg group had a higher frequency of discontinuation due to adverse events and a higher rate of taste-related adverse events. Most taste-related adverse events were mild to moderate.

 

 

 

Reference:

MSD KK receives manufacturing and marketing approval of LYFNUA® Tablets, world’s first selective P2X3 receptor antagonist for the treatment of chronic cough

The world first selective P2X3 receptor antagonist significantly reducing cough frequency!

(source:internet, reference only)


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