Merck announces results from CORALreef AddOn study of enlicitide decanoate

Merck (MRK) announced detailed results from CORALreef AddOn, an active comparator study designed to evaluate the efficacy and safety of enlicitide decanoate compared to other oral non-statin therapies when added to background statins in adults with hypercholesterolemia who have a history of or are at risk for atherosclerotic cardiovascular disease. This is the third positive Phase 3 study of enlicitide decanoate, an investigational, once-daily oral proprotein convertase subtilisin/kexin type 9 inhibitor. In the study, treatment with enlicitide resulted in statistically significant and clinically meaningful reductions in low-density lipoprotein cholesterol compared to bempedoic acid, ezetimibe or bempedoic acid with ezetimibe at eight weeks of treatment. The observed LDL-C reduction resulted in greater LDL-C goal attainment with enlicitide than the comparators. These late-breaking data were presented today at the American College of Cardiology’s Annual Scientific Session and Expo and published simultaneously in JACC. Results from CORALreef AddOn showed that at eight weeks, enlicitide reduced LDL-C by 64.6% from baseline when added to background treatment with a statin. Additionally, enlicitide reduced LDL-C by 56.7% versus bempedoic acid, 36.0% versus ezetimibe and 28.1% versus bempedoic acid with ezetimibe. The overall safety profile was consistent with that observed in the Phase 3 CORALreef Lipids and CORALreef HeFH clinical trials. High adherence with study intervention and dosing instructions were observed across treatment groups. Enlicitide also demonstrated statistically significant reductions at eight weeks across key secondary endpoints. Enlicitide significantly reduced apolipoprotein B by 54.6% compared to baseline versus a 5.4% reduction from baseline with bempedoic acid, a 20.2% reduction from baseline with ezetimibe and a 27.7% reduction from baseline with bempedoic acid with ezetimibe. Additionally, treatment with enlicitide significantly reduced non-high-density lipoprotein cholesterol by 58.0% compared to baseline versus a 5.2% reduction from baseline with bempedoic acid, a 25.1% reduction from baseline with ezetimibe and a 31.8% reduction from baseline with bempedoic acid with ezetimibe. Reduction and goal attainment were also included in the study across a number of measures at eight weeks. Treatment with enlicitide resulted in reductions in lipoprotein of 26.2% compared to baseline versus an increase of 8.1% from baseline with bempedoic acid, no change from baseline with ezetimibe and an increase of 10.4% from baseline with bempedoic acid with ezetimibe. The study also showed that 78.2% of patients treated with enlicitide achieved the prespecified goal of at least 50% reduction in LDL-C along with an LDL-C less than55 mg/dL compared to 2.0% with bempedoic acid, 8.0% with ezetimibe and 20.0% with bempedoic acid with ezetimibe. The safety profile of enlicitide was consistent with that observed in the Phase 3 CORALreef Lipids and CORALreef HeFH trials, with no clinically meaningful differences in incidences of adverse events across the treatment groups. There were no serious AEs, discontinuations due to drug-related AEs or discontinuations due to drug-related SAEs for those treated with enlicitide. In December 2025, the U.S. Food and Drug Administration selected enlicitide to receive the Commissioner’s National Priority Voucher. Merck looks forward to the possibility of bringing enlicitide, which has the potential to be the first approved oral PCSK9 inhibitor, to patients with hypercholesterolemia as quickly as possible.