Key Takeaways
- First oral PCSK9 success: Enlicitide becomes the first oral PCSK9 inhibitor to achieve statistically significant and clinically meaningful LDL-C reduction in Phase 3.
- Positive Phase 3 CORALreef Lipids results: Trial met all primary and key secondary endpoints, showing robust improvements across LDL-C, ApoB, non-HDL-C, and Lp(a).
- Patient-friendly innovation: Oral formulation could shift treatment away from injectables, expanding patient access and adherence.
- Global regulatory plans: Merck intends to file worldwide, with a large cardiovascular outcomes trial already underway.
Breakthrough in Cardiovascular Innovation
Merck announced positive topline Phase 3 results for enlicitide decanoate, its investigational oral PCSK9 inhibitor, in the pivotal CORALreef Lipids study. Enlicitide significantly reduced LDL-C and other atherogenic lipids in patients with hypercholesterolemia on statins—or with statin intolerance—compared to placebo. Importantly, the therapy demonstrated a favorable safety profile with discontinuation rates similar to placebo.
Redefining the PCSK9 Landscape
Current PCSK9 inhibitors are effective but require injection, limiting widespread adoption despite strong clinical benefits. By offering a once-daily oral pill with antibody-like efficacy, enlicitide could overcome one of the biggest barriers to PCSK9 use—patient convenience and adherence—potentially expanding access to millions at risk of atherosclerotic cardiovascular disease (ASCVD).
A Comprehensive Development Program
Enlicitide is being studied in the CORALreef clinical program, which includes the CORALreef Outcomes trial (over 14,500 patients enrolled) to determine its impact on reducing major cardiovascular events such as heart attacks and strokes. Results from CORALreef Lipids add to prior positive Phase 3 trials (CORALreef HeFH and CORALreef AddOn), strengthening Merck’s cardiovascular innovation portfolio.
Merck’s Strategic Perspective
For Merck, enlicitide represents a potential first-in-class oral therapy in a blockbuster category historically dominated by injectable biologics. If approved, enlicitide could redefine cholesterol management, extend PCSK9 therapy beyond specialty settings, and reinforce Merck’s leadership in cardiovascular disease, an area of high unmet global need.
About Enlicitide
Enlicitide is an investigational macrocyclic peptide that inhibits PCSK9 from binding LDL receptors, thereby enhancing clearance of LDL cholesterol from the bloodstream. Unlike currently approved PCSK9 monoclonal antibodies and siRNA therapies, enlicitide is formulated as a daily oral treatment.
About Merck
Merck & Co., Inc., known as MSD outside the U.S. and Canada, is a global biopharmaceutical leader with more than 130 years of advancing science and innovation. With a strong portfolio across oncology, vaccines, infectious diseases, and cardiovascular medicine, Merck is committed to using cutting-edge science to save and improve lives worldwide.
By