Merck's Oral PCSK9 Inhibitor Significantly Lowers LDL-C

Enlicitide decanoate demonstrated greater reductions compared to other non-statin therapies in Phase 3 trial.

Mar. 31, 2026 at 3:22am

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Merck announced positive results from a Phase 3 trial evaluating its investigational oral PCSK9 inhibitor, enlicitide decanoate, which showed statistically significant and clinically meaningful reductions in low-density lipoprotein cholesterol (LDL-C) compared to other oral non-statin therapies when added to background statin treatment.

Why it matters

Enlicitide has the potential to be the first approved oral PCSK9 inhibitor, which could help address the ongoing cardiovascular disease epidemic by enabling robust LDL-C lowering among high-risk patients not at goal on statin therapy.

The details

In the CORALreef AddOn trial, enlicitide reduced LDL-C by 64.6% from baseline at 8 weeks, significantly more than bempedoic acid (56.7% reduction), ezetimibe (36.0% reduction), and bempedoic acid plus ezetimibe (28.1% reduction). Enlicitide also demonstrated greater reductions in secondary endpoints like apolipoprotein B and non-HDL cholesterol.

  • The Phase 3 CORALreef AddOn trial was conducted in 2025.
  • Merck presented the late-breaking data at the American College of Cardiology's Annual Scientific Session and Expo on March 31, 2026.

The players

Merck

A major pharmaceutical company developing enlicitide, an investigational oral PCSK9 inhibitor.

Alberico Catapano

A lead author of the study and professor of pharmacology at the University of Milan.

Dr. Joerg Koglin

Senior vice president and head of general and specialty medicine at Merck Research Laboratories.

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What they’re saying

“Results from CORALreef AddOn demonstrate that enlicitide can significantly reduce LDL-C compared to established oral non-statin treatment options, reinforcing the practice-changing potential of an oral PCSK9 inhibitor.”

— Alberico Catapano, Lead author of the study, professor of pharmacology, University of Milan

“As part of Merck's commitment to help address the CV epidemic, enlicitide was designed to deliver antibody-like LDL-C reduction with a placebo-like safety profile and has the potential to be the first approved oral PCSK9 inhibitor.”

— Dr. Joerg Koglin, Senior vice president, Merck Research Laboratories

What’s next

Merck is continuing to evaluate enlicitide in the large cardiovascular outcomes trial, CORALreef Outcomes, which has completed enrollment with over 14,500 participants.

The takeaway

The consistent positive results from the CORALreef clinical trial program demonstrate the potential for enlicitide, an investigational oral PCSK9 inhibitor, to help address critical unmet needs for patients with hypercholesterolemia and the ongoing cardiovascular disease epidemic.