Enlicitide chloride

Enlicitide demonstrated statistically significant and clinically meaningful reductions in LDL-C in both Phase 3 CORALreef HeFH and CORALreef AddOn trials Enlicitide, a novel macrocyclic peptide, has the potential to be the first approved oral PCSK9 inhibitor RAHWAY, NJ, USA I June 09, 2025 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced positive topline results from the first two of three Phase 3 clinical trials evaluating the safety and efficacy of enlicitide decanoate, an investigational, oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor being evaluated for the treatment of adults with hyperlipidemia on lipid-lowering therapies, including at least a statin. The CORALreef HeFH and CORALreef AddOn trials successfully met their primary and all key secondary endpoints, demonstrating statistically significant and clinically meaningful greater reductions in low-density lipoprotein cholesterol (LDL-C) for enlicitide compared to placebo (CORALreef HeFH) and compared to other oral non-statin therapies (CORALreef AddOn). There were no clinically meaningful differences in incidences of adverse events (AE) and serious adverse events (SAE) in either trial. Results from the three Phase 3 trials in the CORALreef clinical development program will be presented at a future scientific congress. Key takeaways from CORALreef HeFH and CORALreef AddOn studies: “We are thrilled to bring forward the first Phase 3 results from our clinical development program evaluating enlicitide, which, if approved, would be the first marketed oral PCSK9 inhibitor in the U.S.,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “Enlicitide is a novel macrocyclic peptide that has the potential to deliver antibody-like efficacy and specificity for the validated PCSK9 mechanism in the form of a daily oral pill. We are working with urgency to make this oral therapy available to patients worldwide.” “Atherosclerotic cardiovascular disease accounts for 85 percent of cardiovascular deaths. Despite available treatment options, cardiovascular-related deaths remain the leading cause of death worldwide and continue to rise,” said Dr. Christie M. Ballantyne, principal investigator of the CORALreef HeFH study and Professor of Medicine at Baylor College of Medicine. “LDL-C is a major modifiable risk driver for atherosclerosis and prioritization of LDL-C management should be a cornerstone of cardiovascular risk prevention. Early intervention and intensification of lipid treatment would allow more patients to achieve LDL-C goals.” The efficacy and safety of enlicitide are being evaluated through the comprehensive CORALreef Phase 3 clinical development program , which aims to enroll approximately 17,000 patients across several trials, including two large ongoing trials, CORALreef Lipids and CORALreef Outcomes. About CORALreef HeFH CORALreef HeFH ( NCT05952869 ) is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of enlicitide compared to placebo in adults with HeFH who have a history of or were at risk for a major ASCVD event and are treated with a moderate or high intensity statin with or without other lipid-lowering therapies. The primary endpoints were mean percent change from baseline in LDL-C at week 24, number of participants with one or more adverse events (AEs), and number of participants who discontinued study drug due to an AE. Secondary endpoints included mean percent change from baseline in LDL-C at week 52, mean percent change from baseline in non-HDL-C, ApoB and percent change in Lp(a) at week 24. About CORALreef AddOn CORALreef AddOn ( NCT06450366 ) is a Phase 3, randomized, double-blind, multicenter study designed to evaluate the efficacy and safety of enlicitide compared to ezetimibe, to bempedoic acid, and to ezetimibe and bempedoic acid, in patients with hypercholesterolemia who had a history of a major ASCVD event or were at risk for a major ASCVD event and are treated with a statin. The primary endpoint was the mean percent change from baseline in LDL-C at week 8. Secondary endpoints included mean percent change from baseline in non-HDL-C and ApoB. About enlicitide and PCSK9 Enlicitide is an investigational, potentially first oral PCSK9 inhibitor designed to lower LDL-C via the same biological mechanism as currently approved monoclonal antibody injectable PCSK9 inhibitors but in a daily pill form. Enlicitide is a novel oral macrocyclic peptide that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors. PCSK9 plays a key role in cholesterol homeostasis by regulating levels of the LDL receptor, which is responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 with enlicitide prevents the interaction of PCSK9 with LDL receptors. This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood. About hyperlipidemia Hyperlipidemia is a disorder characterized by an excess of lipids or fats in the blood, affecting approximately 86 million adults (aged 20 and older) in the U.S. Despite adjusting diet or other lifestyle factors, some individuals may not reach recommended lipid levels and will require medication to treat and manage hyperlipidemia.Hyperlipidemia is a major risk driver for the development of ASCVD events, such as heart attacks and strokes, which account for 85 percent of cardiovascular deaths. Merck’s focus on cardiovascular disease Merck has a long history of developing treatments for cardiovascular disease. More than 60 years ago, we introduced our first cardiovascular therapy—and our scientific efforts to understand and treat cardiovascular-related disorders have continued. Cardiovascular disease continues to be one of the most serious health challenges of the 21st century, and is the leading cause of death worldwide. Approximately 18 million people across the globe die from cardiovascular disease every year; in the United States, one person dies every 36 seconds from cardiovascular disease. Advancements in the treatment of cardiovascular disease can make a critical difference for patients and health systems around the world. At Merck, we strive for scientific excellence and innovation in all stages of research, from discovery through approval and life cycle management. We work with experts throughout the cardiovascular and pulmonary community to advance research that can help improve the lives of patients globally. Information for other currently enrolling cardiovascular studies can be found by visiting: https://www.merckclinicaltrials.com/cardiovascular . 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 X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . SOURCE: Merck

Two trials form part of Merck & Co.’s wider CORALreef development program, which includes the ongoing CORALreef Lipids and CORALreef Outcomes phase 3 studies.\n Merck & Co.’s ambition to get the first oral PCSK9 inhibitor to market came one step closer this morning as the pharma unveiled a pair of phase 3 wins for enlicitide decanoate in patients with high cholesterol.Merck evaluated the candidate in two studies, including the CORALreef HeFH trial of patients with heterozygous familial hypercholesterolemia who had suffered from, or had a risk of, atherosclerotic cardiovascular disease and were being treated with a statin. The trial hit its primary endpoint of showing a clinically meaningful reduction in baseline levels of low-density lipoprotein cholesterol (LDL-C) at Week 24 compared to placebo, Merck explained in a June 9 release.When it came to the CORALreef AddOn study of hypercholesterolemia patients, the study also hit its key endpoint of showing a reduction in LDL-C at Week 8 compared to the approved non-statin cholesterol medicines ezetimibe or bempedoic acid.Merck didn’t divulge any detailed data behind the wins, only noting that there were “no clinically meaningful differences in incidences of adverse events” in either trial. The two studies form part of the company’s wider CORALreef development program, which spans 17,000 patients in total and also includes the ongoing CORALreef Lipids and CORALreef Outcomes phase 3 trials.The hypercholesterolemia market is currently dominated by injectable PCSK9 inhibitors in the form of Amgen’s Repatha and Sanofi-Regeneron’s Praluent. Meanwhile, Novartis’ Leqvio uses small-interfering RNA technology to decrease PCSK9 production in the liver.Enlicitide uses the same mechanism as approved monoclonal antibody injectable PCSK9 inhibitors but would give patients an oral alternative, potentially making it more attractive in terms of administration.  Today’s double win keeps Merck ahead of its rival AstraZeneca when it comes to getting the first oral PCSK9 inhibitor to regulators. The British-based pharma’s option is AZD0780, which was shown to halve cholesterol in a phase 2 dyslipidemia study in March.“We are thrilled to bring forward the first phase 3 results from our clinical development program evaluating enlicitide, which, if approved, would be the first marketed oral PCSK9 inhibitor in the U.S.,” Dean Li, M.D., Ph.D., president of Merck Research Laboratories, said in the release.“Enlicitide is a novel macrocyclic peptide that has the potential to deliver antibody-like efficacy and specificity for the validated PCSK9 mechanism in the form of a daily oral pill,” Li added. “We are working with urgency to make this oral therapy available to patients worldwide.”Citi analysts described this morning’s data as “encouraging” ahead of an anticipated approval in 2027.“We believe enlicitide could be a key player in the hyperlipidemia space, where an oral administration along with a positive efficacy and safety profile could be differentiating,” the analysts wrote in a June 9 note.Merck was up 2% premarket Monday morning on the news.