Merck Presents Positive Phase 3 Data for Oral PCSK9 Inhibitor Enlicitide at ACC.26
核心洞察
Merck (搜索) announced positive results from the Phase 3 CORALreef AddOn trial evaluating enlicitide decanoate, an investigational once-daily oral PCSK9 inhibitor, compared to ezetimibe, bempedoic acid, and combination therapy in statin-treated adults with hypercholesterolemia (搜索).
Enlicitide has the potential to be the first approved oral PCSK9 inhibitor, designed to lower LDL-C via the same biological mechanism as currently approved injectable PCSK9 inhibitors but in daily pill form.
The comprehensive CORALreef Clinical Trial program is evaluating over 19,000 participants with hypercholesterolemia (搜索), with enlicitide demonstrating statistically significant and clinically meaningful LDL-C reductions in three pivotal Phase 3 studies.
Merck (搜索) announced positive results from the Phase 3 CORALreef AddOn trial evaluating enlicitide decanoate, an investigational once-daily oral PCSK9 inhibitor, at the American College of Cardiology's Annual Scientific Session and Expo (ACC.26) in New Orleans from March 28-30, 2026. The trial compared enlicitide's efficacy and safety versus ezetimibe, bempedoic acid, and combination therapy with ezetimibe and bempedoic acid in adults with hypercholesterolemia (搜索) who are treated with a statin.
"The data planned for presentation at ACC will underscore the strength and momentum of Merck (搜索)'s cardio-pulmonary pipeline as we work to advance research that helps address the CV epidemic impacting millions with atherosclerosis," said Dr. Joerg Koglin, senior vice president, head of general and specialty medicine, global clinical development, Merck Research Laboratories.
Enlicitide: Potential First-in-Class Oral PCSK9 Inhibitor
Enlicitide has the potential to be the first approved oral PCSK9 inhibitor, designed to lower LDL-C via the same biological mechanism as currently approved monoclonal antibody, injectable PCSK9 inhibitors but in a daily pill form. The investigational novel macrocyclic peptide binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors.
PCSK9 plays a key role in cholesterol homeostasis by regulating levels of the LDL receptor (搜索), which is responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 prevents the interaction of PCSK9 with LDL receptors, resulting in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood.
Comprehensive CORALreef Clinical Program
The efficacy and safety profile of enlicitide is being evaluated through the comprehensive CORALreef Clinical Trial program evaluating over 19,000 participants who have hypercholesterolemia (搜索). Enlicitide demonstrated statistically significant and clinically meaningful reductions in LDL-C in three pivotal Phase 3 studies: CORALreef Lipids (NCT05952856), CORALreef HeFH (NCT05952869) and CORALreef AddOn (NCT06450366).
Enlicitide is continuing to be evaluated in the large cardiovascular outcomes trial, CORALreef Outcomes (NCT06008756), which has completed enrollment with over 14,500 participants. Additional CORALreef clinical trials include CORALreef Extension (NCT06492291), CORALreef Pediatric (NCT07058077) and CORALreef Combination (NCT07216482).
Addressing Unmet Medical Need in Hypercholesterolemia
Hypercholesterolemia (搜索), a type of hyperlipidemia, is a disorder in which there are elevated LDL-C levels in the blood. It affects approximately 86 million adults in the U.S. and is a major risk factor for atherosclerotic cardiovascular disease (搜索) (ASCVD). Nearly 70% of people with ASCVD who are treated with lipid lowering therapies do not reach target LDL cholesterol levels.
The silent CV epidemic is the leading cause of deaths globally, contributing to the majority of heart attacks and strokes, and deaths related to CV continue to rise. ASCVD accounts for 85% of CV deaths and is caused by the buildup of plaque within the arteries, leading to narrowed or blocked blood vessels that can result in serious CV events such as heart attacks and strokes as well as coronary artery disease, peripheral artery disease and cerebrovascular disease.
WINREVAIR Data in Pulmonary Hypertension
Merck (搜索) also presented positive results from the Phase 2 CADENCE trial evaluating WINREVAIR (sotatercept-csrk (搜索)) in adults with combined post- and precapillary pulmonary hypertension and heart failure with preserved ejection fraction (搜索) (CpcPH-HFpEF). WINREVAIR is FDA-approved for the treatment of adults with pulmonary arterial hypertension (搜索) (PAH) and is the first activin signaling inhibitor therapy approved to treat PAH.
CpcPH-HFpEF is a distinct, identifiable and well-characterized condition that develops in people with long-term or advanced heart failure. Different from Group 1 pulmonary arterial hypertension (搜索) (PAH), CpcPH-HFpEF is caused by two interrelated components: pulmonary vascular disease and cardiac disease. The condition is thought to be uncommon and underdiagnosed, typically impacting people who are older and have other comorbid conditions. It is associated with a worse prognosis and higher mortality rate compared to HFpEF alone, and there are no treatments specifically approved for CpcPH-HFpEF.