Merck announced the first results from the Phase 3 CORALreef HeFH trial, showing that its investigational drug enlicitide decanoate, a once-daily oral PCSK9 inhibitor, reduced LDL-C by 59.4% compared to placebo in adults with heterozygous familial hypercholesterolemia (HeFH) after 24 weeks.
This effect was similar to results from the Phase 3 CORALreef Lipids study. The findings will be presented at the 2025 AHA Scientific Sessions and published in the Journal of the American Medical Association.
In the CORALreef HeFH trial, enlicitide showed significant reductions in LDL-C (bad cholesterol) at 24 weeks, the main goal of the study. It also showed positive results for secondary measures, including LDL-C at 1 year (week 52), as well as non-HDL-C, apolipoprotein B (ApoB), and lipoprotein(a) (Lp(a)) at 24 weeks in adults with heterozygous familial hypercholesterolemia (HeFH), who were also on stable lipid-lowering therapy, including moderate or high-intensity statins.
The drug's safety was similar to that of a placebo, and patients had high adherence to the treatment and dosing instructions (97% and 96%, respectively).
Executive Statement
According to Dr. Christie M. Ballantyne, a lead author of the CORALreef HeFH study and Professor of Medicine at Baylor College of Medicine, 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. 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.