Merck's New Cholesterol Drug Shows Promising Results in CORALreef Trial

Merck & Co. (MRK) reported positive results from the CORALreef trial, testing a new cholesterol-lowering medicine called enlicitide decanoate. The study showed the drug effectively lowered LDL cholesterol and other blood fats without causing more side effects than a placebo. Merck plans to present these results to global health authorities and discuss them at future meetings as part of the CORALreef program to help individuals with uncontrolled cholesterol.

Merck & Co. (MRK) has announced positive topline results from the Phase 3 CORALreef Lipids trial, demonstrating the efficacy of enlicitide decanoate in reducing LDL cholesterol and other key atherogenic lipids. The study, conducted in adults with hypercholesterolemia, showed statistically significant and clinically meaningful reductions in LDL-C compared to placebo at Week 24. Enlicitide also demonstrated significant reductions in non-HDL-C, apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)] [1].

The trial, which enrolled over 1,000 participants, met all primary and key secondary endpoints. Merck plans to share these results with regulatory authorities worldwide and will present the data at a future scientific congress. Enlicitide, an investigational oral PCSK9 inhibitor, is designed to lower LDL-C via the same biological mechanism as currently approved monoclonal antibody, injectable PCSK9 inhibitors but in a daily pill form [1].

The study's primary objective was to assess whether enlicitide decanoate was superior to placebo in reducing LDL-C, as measured by mean percent change from baseline at Week 24. Key secondary efficacy endpoints included changes from baseline in LDL-C at week 52 and changes from baseline in other key atherogenic lipids at week 24 [1].

Enlicitide has shown promising results in previous Phase 3 trials, including CORALreef HeFH and CORALreef AddOn, which also demonstrated significant LDL-C lowering. The CORALreef program reflects Merck’s commitment to advancing research to help address the global burden of atherosclerotic cardiovascular disease [1].

Hypercholesterolemia, a major risk factor for ASCVD, affects approximately 86 million adults in the U.S. and is a leading cause of cardiovascular deaths. The trial results suggest that enlicitide decanoate could provide a new oral option for patients struggling to meet their cholesterol goals with current treatments [1].

Merck continues to focus on cardiovascular disease, with a long history of developing treatments for this condition. The company’s commitment to scientific excellence and innovation is evident in the CORALreef Clinical Trial program, which includes the large cardiovascular outcomes trial, CORALreef Outcomes, with over 14,500 participants [1].

References:
[1] Merck. (September 2, 2025). Merck reports positive topline results from CORALreef Lipids trial evaluating enlicitide decanoate. Retrieved from https://www.merck.com/news/mercks-investigational-oral-pcsk9-inhibitor-enlicitide-decanoate-met-all-primary-and-key-secondary-endpoints-in-adults-with-hypercholesterolemia-in-pivotal-coralreef-lipids-study/