Merck (MSD outside the US and Canada) reported positive topline results from its phase 3 CORALreef Lipids trial. The study evaluated enlicitide decanoate, a once-daily oral PCSK9 inhibitor, in adults with hypercholesterolemia already on moderate or high-intensity statins—or with documented statin intolerance.
Strong Phase 3 Results
- The trial met all primary and key secondary endpoints.
- LDL-C reduction was statistically significant and clinically meaningful at 24 weeks compared with placebo.
- Benefits extended to other atherogenic lipids:
- Non-HDL-C
- Apolipoprotein B (ApoB)
- Lipoprotein(a) [Lp(a)] - Safety profile: Adverse events, including serious ones, were similar between treatment and placebo groups. Few participants discontinued due to side effects.
Trial Design and Scale
- Largest completed phase 3 study for enlicitide in patients with high LDL-C and elevated cardiovascular risk despite statins.
- Enrolled adults with prior ASCVD events or increased risk for first events.
- Randomized, double-blind, placebo-controlled setup.
- Primary objective: LDL-C reduction at Week 24.
- Secondary endpoints: LDL-C at Week 52 and changes in ApoB, non-HDL-C, and Lp(a).
Expert Perspectives
Dr. Dean Y. Li, president of Merck Research Laboratories:
“Enlicitide is the first oral macrocyclic peptide PCSK9 inhibitor with statistically significant LDL-C lowering in phase 3 trials. If approved, it could redefine LDL management.”
Dr. Ann Marie Navar, UT Southwestern Medical Center:
“Enlicitide may help more patients meet guideline targets and reduce ASCVD risk, complementing current lipid-lowering strategies.”
The CORALreef Program
The CORALreef clinical trial program evaluates enlicitide across multiple settings:
- CORALreef HeFH and CORALreef AddOn already showed strong LDL-C reductions.
- CORALreef Outcomes, a cardiovascular outcomes study with over 14,500 participants, has completed enrollment.
Why It Matters
- PCSK9 inhibitors block the PCSK9 protein, increasing LDL receptor availability and boosting LDL clearance.
- Existing therapies are injectable. Enlicitide delivers similar efficacy in an oral pill.
- Hypercholesterolemia affects 86 million US adults and drives 85% of cardiovascular deaths.
- Nearly 70% of patients with ASCVD fail to reach LDL-C targets despite therapy.
Broader Impact
- Cardiovascular disease kills 18 million people globally each year.
- In the US, one person dies every 36 seconds from cardiovascular-related causes.
- Merck has a 60-year legacy in cardiovascular medicine and continues to advance lipid and ASCVD treatment through innovation.
Merck plans to share detailed CORALreef Lipids results with regulators worldwide and present them at an upcoming scientific congress.
