Merck’s Enlicitide Decanoate, an Investigational Oral PCSK9 Inhibitor, Significantly Reduced LDL-C in Adults with Heterozygous Familial Hypercholesterolemia (HeFH) in Phase 3 CORALreef HeFH Trial

Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the first presentation of results from the pivotal Phase 3 CORALreef HeFH trial demonstrating that treatment with enlicitide decanoate, an investigational, once-daily oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, resulted in a statistically significant and clinically meaningful reduction in low-density lipoprotein cholesterol (LDL-C) of 59.4% compared to placebo at week 24 (95% CI: -65.6, -53.2; p<0.001) in adults with heterozygous familial hypercholesterolemia (HeFH). The effect size and safety profile was comparable to that observed in the pivotal Phase 3 CORALreef Lipids study. These late-breaking data will be presented for the first time today at the American Heart Association (AHA) Scientific Sessions 2025 (Abstract #4391641) and published simultaneously in the Journal of the American Medical Association.

In CORALreef HeFH, enlicitide demonstrated statistically significant and clinically meaningful reductions in LDL-C at week 24 (primary endpoint) and statistically significant reductions in secondary endpoints including LDL-C at one year (week 52), and non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and lipoprotein(a) (Lp(a)) at week 24, in adults with HeFH receiving stable background lipid-lowering therapy including at least moderate or high intensity statin therapy. The overall safety profile was comparable to placebo. High adherence with study intervention (97%) and dosing instructions (96%) were observed across treatment groups.

“Data from CORALreef HeFH demonstrate the potential for enlicitide to help address critical unmet needs for adults with heterozygous familial hypercholesterolemia are at risk for premature atherosclerotic cardiovascular events yet a significant portion of patients do not achieve guideline-recommended LDL-C level despite available lipid-lowering therapies,” said Dr. Christie M. Ballantyne, a lead author of the CORALreef HeFH study and Professor of Medicine at Baylor College of Medicine. “As the potentially first approved oral PCSK9 inhibitor, enlicitide was designed to provide efficacy similar to anti-PCSK9 monoclonal antibodies and may be an important new treatment option to help adults with heterozygous familial hypercholesterolemia reach their guideline-recommended LDL-C goal. Lowering elevated LDL-C levels helps reduce the risk of atherosclerotic cardiovascular disease.”