Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of gefapixant, an investigational, non-narcotic, oral selective P2X3 receptor antagonist, developed for the treatment for adults with refractory or unexplained chronic cough. The CHMP’s recommendation will now be reviewed by the European Commission (EC) for marketing authorization in the European Union (EU) and a final decision is expected later this year.

“Today’s positive CHMP opinion is the next step for gefapixant to become the first treatment approved in the European Union for adults with refractory or unexplained chronic cough,” said Dr. Joerg Koglin, senior vice president, global clinical development, Merck Research Laboratories. “Refractory or unexplained chronic cough as a condition with often disruptive, uncontrolled coughing associated with major physical, social and emotional consequences represents a large unmet clinical need.”

The CHMP’s positive opinion is based on results from the COUGH-1 and COUGH-2 clinical trials, which are the first companion Phase 3 studies ever completed in patients with refractory or unexplained chronic cough, a cough that persists despite appropriate treatment of underlying conditions or for which the underlying cause cannot be identified despite a thorough evaluation. Both studies met the primary endpoint, demonstrating a statistically significant reduction in 24-hour cough frequency in adults treated with gefapixant 45 mg twice daily versus placebo at 12 weeks (COUGH-1) and 24 weeks (COUGH-2).

About the COUGH-1 and COUGH-2 trials

COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) are Phase 3 multinational, randomized, double-blind, placebo-controlled studies that evaluated the efficacy and safety of gefapixant in reducing cough frequency in adult participants with refractory chronic cough (RCC) or unexplained chronic cough (UCC). A total of 2,044 participants were treated in COUGH-1 (n=730) and COUGH-2 (n=1,314). In both studies, patients were randomly selected to receive one of the following: gefapixant 45 mg twice daily, gefapixant 15 mg twice daily, or placebo. The primary efficacy outcomes for COUGH-1 and COUGH-2 were 24-hour cough frequency at week 12 and 24-hour cough frequency at week 24, respectively, measured using an ambulatory digital audio recording device. Secondary endpoints included awake cough frequency and percentage of participants with a greater than 1.3-point increase from baseline in the Leicester Cough Questionnaire (LCQ) total score. COUGH-1 had a 12-week treatment period and a 40-week safety-extension period, while COUGH-2 had a 24-week treatment period and a 28-week safety-extension period.

In these studies, adults treated with gefapixant 45 mg twice daily demonstrated a statistically significant reduction in 24-hour cough frequency (measured objectively, as coughs per hour, using 24-hour sound recordings) versus placebo at 12 weeks (COUGH-1) (18.45% reduction relative to placebo, 95% CI [-32.92, -0.9; p=0.041]) and 24 weeks (COUGH-2) (14.64% reduction relative to placebo, 95% CI [-26.01, -1.4; p=0.031]). The gefapixant 15 mg twice daily treatment arms did not meet the primary efficacy endpoint in either Phase 3 study. The Phase 3 study results were published in The Lancet.

In 2022, Merck announced that additional analyses were underway to address questions received from regulatory authorities. The questions were primarily related to the cough counting system used in generating the Phase 3 data, on which the marketing authorization application for gefapixant was based. The results of the additional analyses were generally consistent with the published Phase 3 results from COUGH-1 and COUGH-2.

About gefapixant

Gefapixant is an investigational, orally administered, selective P2X3 receptor antagonist, for the potential treatment of refractory or unexplained chronic cough. P2X3 receptors are one of the receptor types found on sensory nerve fibers, predominantly C fibers, in the airway lining. Chemical stimuli, including adenosine triphosphate (ATP), can be released from airway lining cells due to airway inflammation, irritation, and mechanical stress/injury. Binding of extracellular ATP to P2X3 receptors on C fibers in the airway can be sensed as a signal of potential damage, creating an action potential, which may initiate coughing. The inhibition of binding of extracellular ATP to P2X3 receptors is thought to reduce sensory nerve activation and, subsequently, cough.

In 2022, gefapixant under the brand name LYFNUA^®, was approved in Japan and Switzerland for treatment of adults with refractory or unexplained chronic cough.

About chronic cough

The prevalence of chronic cough (a cough lasting more than 8 weeks) is estimated to be approximately 5 to 10% of adults globally. In a subset of these cases, patients either do not respond to treatment of underlying conditions (such as asthma or gastroesophageal reflux), known as refractory chronic cough (RCC), or they have no identifiable underlying condition despite a thorough evaluation, known as unexplained chronic cough (UCC). In the EU, there are currently no approved therapies for the treatment of RCC or UCC.

About Merck

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

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