Enlicitide

Merck announced positive Phase 3 CORALreef HeFH trial results for enlicitide, a once-daily oral PCSK9 inhibitor, at AHA 2025. The study demonstrated a significant 59.4% LDL-C reduction compared to placebo at week 24 in adults with HeFH. Enlicitide also showed improvements in other lipid parameters with a safety profile comparable to placebo. It is designed to deliver antibody-like efficacy, addressing unmet needs in HeFH patients and potentially becoming the first approved oral PCSK9 inhibitor. The results were published in the *Journal of the American Medical Association.*

Merck’s Phase 3 CORALreef Lipids trial revealed that enlicitide, an investigational oral PCSK9 inhibitor, significantly reduced LDL-C levels by 55.8% in adults with or at risk for ASCVD. The study demonstrated sustained reductions at one year and improvements in other lipid parameters. Enlicitide’s safety profile was comparable to placebo, with high treatment adherence. The oral formulation may address unmet needs in ASCVD management due to the availability of current injectable PCSK9 inhibitors. Merck plans to seek regulatory approval based on these findings and other CORALreef trials.