Merck announced positive topline results from the pivotal Phase 3 CORALreef Lipids trial evaluating enlicitide decanoate, an investigational, once-daily oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for adults with hypercholesterolemia. The trial enrolled participants on moderate or high-intensity statins, as well as those with documented statin intolerance. 

Enlicitide achieved all primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful reductions in low-density lipoprotein cholesterol (LDL-C) compared to placebo at Week 24. Notably, significant improvements were also observed in other atherogenic lipids, including non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)]. The safety profile of enlicitide was favorable, with adverse events, serious adverse events, and discontinuation rates comparable between treatment groups. 

CORALreef Lipids is the largest Phase 3 study of enlicitide to date, involving a broad population with elevated LDL-C and either a history of or increased risk for major atherosclerotic cardiovascular disease events despite statin therapy. Merck plans to share these results with regulatory authorities globally and present the data at a forthcoming scientific congress. 

“This is the third Phase 3 trial to demonstrate clinically meaningful and statistically significant LDL-C lowering for enlicitide,” said Dr. Dean Y. Li, President of Merck Research Laboratories. “Injectable PCSK9 inhibitors have already transformed cholesterol management, and enlicitide, as the first oral macrocyclic peptide PCSK9 inhibitor, offers antibody-like efficacy in an oral form. If approved, it could redefine how patients manage LDL levels, providing a convenient new option to achieve their treatment goals.” 

Dr. Ann Marie Navar, a lead investigator of the study and Associate Professor of Medicine at UT Southwestern Medical Center, added, “These results strengthen the growing evidence supporting enlicitide’s ability to lower LDL cholesterol and other key atherogenic lipids. Enlicitide has the potential to help more patients reach guideline-recommended lipid targets and reduce their long-term cardiovascular risk, which is currently being further evaluated in ongoing cardiovascular outcomes trials.”