Merck Announces Positive Topline Results from Two Pivotal Phase 3 Trials of Enlicitide Decanoate, the First Oral Macrocyclic Peptide PCSK9 Inhibitor

On June 9, MSD announced positive topline results from the first two of three Phase 3 clinical trials, which evaluatedEstimatedenlicitide decanoateTheSafety and effectiveness,enlicitideIs an investigational oral PCSK9 inhibitor being evaluated for lipid-lowering therapy in adults with hyperlipidemia, including those on at least one statin. Compared with placebo (CORALreef HeFH) and other oral non-statin therapies (CORALreef AddOn),enlicitideLDL-C was statistically significantly reduced with clinical significance. In the two trials, the incidence of adverse events (AE) and serious adverse events (SAE) showed no clinically meaningful differences.Enlicide is a novel oral macrocyclic peptide that binds to PCSK9 and inhibits the interaction between PCSK9 and the LDL receptor.

Results from three Phase 3 trials in the CORALreef clinical development program will be presented at future scientific conferences.

Key Points of the CORALreef HeFH and CORALreek AddOn Studies:

CORALreef HeFH: In heterozygous familial hypercholesterolemia (HeFH) adults with a history of or at risk for atherosclerotic cardiovascular disease (ASCVD),enlicitideCompared with placebo, the reduction in LDL-C was statistically and clinically significant in patients treated with statins.

CORALreef AddOn: In adults with hyperlipidemia who have a history of ASCVD or are at risk of ASCVD and are receiving statin therapy,enlicitideEzetimibe, Bempedoic Acid, and EzetimibeClothAndBempedoic AcidIn comparison, the reduction in LDL-C is statistically significant and clinically meaningful.

Dr. Dean Y. Li, President of Merck & Co., Inc. Research Laboratories, said:"We are pleased to announce the first Phase 3 results from our clinical development program evaluating enlicide, which, if approved, would be the first oral PCSK9 inhibitor to be launched in the United States.enlicideBempedoic AcidIt is a novel macrocyclic peptide that has the potential to deliver antibody-like efficacy and specificity for the proven PCSK9 mechanism in the form of a daily oral pill. We are urgently working to make this oral therapy available to patients worldwide."

Christie M. Ballantyne, MD, Chief Investigator of the CORALreef HeFH Study and Professor of Medicine at Baylor College of Medicine, said:"Atherosclerotic cardiovascular disease accounts for 85% of cardiovascular deaths. Despite available treatment options, cardiovascular-related mortality remains a leading cause of death worldwide and continues to rise. LDL-C is the primary modifiable risk driver of atherosclerosis, and prioritizing LDL-C management should be the cornerstone of cardiovascular risk prevention. Early intervention and enhanced lipid therapy will enable more patients to achieve LDL-C goals."

EnlicideThe efficacy and safety are being evaluated through the comprehensive CORALreef Phase 3 clinical development program, which aims to recruit approximately 17,000 patients across multiple trials, including two ongoing large-scale trials, CORALreef Lipids and CORALreef Outcomes.