Enlicitide Lowers LDL-C Consistently Across PREVENT CVD Risk Categories

Enlicitide has produced consistent LDL-C lowering across all baseline PREVENT cardiovascular risk categories, according to an analysis of the CORALreef Lipids study.¹

These data were presented at the American Heart Association (AHA) Scientific Sessions 2026 in Chicago, Illinois, by Christie Ballantyne, MD, chief of cardiology and cardiovascular research and director for cardiometabolic disease prevention at Baylor College of Medicine.¹

“One of the exciting things about enlicitide and the CORALreef program has been the consistency of data in the trials,” Ballantyne told HCPLive in an exclusive interview. “One of the things we always like to see is when you’re doing different trials and different subsets, you have consistent data. And I think this is an instance where we take a pretty straightforward therapy – it’s only one dose, 20 mg – and you’re getting substantial LDL-C reductions.”

CORALreef Lipids was a multinational, double-blind, randomized, placebo-controlled trial evaluating enlicitide’s efficacy in patients with a history of a major atherosclerotic cardiovascular disease (ASCVD) event who had elevated LDL-C levels. Patients were eligible for inclusion if they had LDL-C ≥55 mg/dL and were being treated with a moderate- or high-intensity statin, among other criteria. Those with a history of homozygous familial hypercholesterolemia or heart failure, or those who were undergoing an LDL-C apheresis program within 3 months prior to first study visit, were excluded.^2,3

Patients were randomly assigned in a 2:1 ratio to either enlicitide 20 mg or placebo daily for 52 weeks. The primary endpoint was mean percent change in LDL-C from baseline to week 24. Key secondary endpoints included mean percent change in LDL-C at week 52,and the mean percent change in non-HDL-C, apolipoprotein B (ApoB), and lipoprotein(a) (Lp(a)) levels at week 24.³

A total of 2909 patients were enrolled in the trial, of whom 1935 were assigned to enlicitide and 969 to placebo. Mean age was 63 years, and mean LDL-C level at baseline was 96.1 mg/dL (+/- standard deviation [SD], 38.9 mg/dL). By week 24, mean LDL-C change was -57.1% (95% CI, -61.8 to -52.5) with enlicitide and 3% (95% CI, 0.9 to 5.1) with placebo. This represented an adjusted between-group difference of -55.8% (95% CI, -60.9 to -50.7; P <.001).³

In the present analysis, Ballantyne and colleagues included a total of 843 patients, 573 from the enlicitide arm and 270 from the placebo arm. Baseline PREVENT 10-year risk was categorized as low (<3%), borderline (3 to 5%), intermediate (5 to <10%), or high (≥10%) risk. Percent change from baseline in LDL-C was assessed across PREVENT risk categories, while additional analyses evaluated the percent changes in ApoB, Lp(a), and non-HDL-C.¹

Of the included patients, 8.2% were categorized as low-risk, 18.3% as borderline, 44% as intermediate, and 29.5% as high risk. Mean age increased with PREVENT risk, rising from 48.8 to 70.4 years. At week 24, placebo-corrected mean percent changes from baseline in LDL-C were -62.6% in low-risk patients, -57.6% in borderline risk, -57.1% in intermediate risk, and -58% in high-risk PREVENT strata. Ballantyne and colleagues also saw reductions in Lp(a), ApoB, and non-HDL-C across all strata.¹

Ultimately, Ballantyne and colleagues determined that enlicitide effectively and consistently reduced LDL-C across all baseline PREVENT cardiovascular risk categories, with corresponding reductions in other key markers of cholesterol. Ballantyne addressed the implications of these data for the safety and efficacy of enlicitide, particularly in advance of the ongoing outcomes trial.¹

“There’s a very large outcomes trial that’s fully enrolled – we haven’t heard anything from that, but I think we can have enough confidence in what we have now,” Ballantyne said. “If someone doesn’t want to take an injectable, we have another option which gives the same efficacy as that injectable: an easy once-a-day pill.”

Editors’ Note: Ballantyne reports disclosures with Abbott, Amgen, Arrowhead, AstraZeneca, Eli Lilly, Genentech, and others.

References

1. Navar A, Banka P, Wumesh K, et al. Efficacy of Enlicitide on LDL-C Reduction Across PREVENT Cardiovascular Risk Categories in the Phase 3 CORALreef Lipids Study. Presented at the American Heart Association (AHA) Scientific Sessions 2026, Chicago, IL. November 6-9, 2026.

2. Merck Sharp & Dohme. A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids. ClinicalTrials.gov Identifier: NCT05952856. Updated September 24, 2026. Accessed November 11, 2026. https://clinicaltrials.gov/study/NCT05952856

3. Navar AM, Mikhailova E, Catapano AL, et al. A placebo-controlled trial of the oral PCSK9 inhibitor enlicitide. New England Journal of Medicine. 2026;394(6):529-539. doi:10.1056/nejmoa2511002