Merck’s enlicitide shows promise in lowering LDL-C

Published 09/06/2025, 11:50
Merck’s enlicitide shows promise in lowering LDL-C

RAHWAY, N.J. - Merck & Co., Inc. (NYSE: MRK) today shared positive results from two Phase 3 clinical trials for enlicitide, an investigational oral cholesterol-lowering medication. The trials, named CORALreef HeFH and CORALreef AddOn, have met their primary and key secondary endpoints, showing significant reductions in low-density lipoprotein cholesterol (LDL-C) compared to placebo and other oral non-statin therapies.

Enlicitide, a novel macrocyclic peptide, is poised to be the first oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor if it receives regulatory approval. PCSK9 inhibitors work by increasing the number of LDL receptors on cell surfaces, thereby enhancing the removal of LDL cholesterol from the bloodstream.

The CORALreef HeFH trial focused on patients with heterozygous familial hypercholesterolemia (HeFH), a genetic condition that leads to high LDL-C levels. Participants in this trial were already on statin therapy, and enlicitide demonstrated significant LDL-C reductions versus placebo. The CORALreef AddOn study compared enlicitide to other oral therapies like ezetimibe and bempedoic acid in adults with hyperlipidemia, also yielding favorable results for enlicitide.

There were no clinically meaningful differences in the incidence of adverse events or serious adverse events between enlicitide and the control groups in either study. Dr. Dean Y. Li, president of Merck Research Laboratories, expressed enthusiasm about bringing enlicitide to market as a daily oral pill that could offer antibody-like efficacy for managing cholesterol.

The importance of managing LDL-C levels to prevent atherosclerotic cardiovascular disease, which accounts for a majority of cardiovascular deaths, was underscored by Dr. Christie M. Ballantyne, principal investigator of the CORALreef HeFH study. Merck’s extensive history in cardiovascular therapies, combined with its strong financial health score of "GREAT" from InvestingPro and 55-year track record of consistent dividend payments, adds context to the potential significance of enlicitide in the treatment landscape.

The comprehensive CORALreef Phase 3 clinical development program is ongoing and aims to enroll approximately 17,000 patients across several trials. These include the CORALreef Lipids and CORALreef Outcomes trials, which continue to investigate enlicitide’s efficacy and safety.

As cardiovascular disease remains the leading cause of death worldwide, advancements in treatment, such as enlicitide, could have a substantial impact on patient health and healthcare systems globally. The results from the CORALreef trials are expected to be presented at a future scientific congress. This announcement is based on a press release statement from Merck & Co., Inc.

In other recent news, Merck has reported promising results from its Phase 1 KANDLELIT-001 study, evaluating the investigational cancer drug MK-1084. The drug showed positive safety and efficacy in patients with KRAS G12C-mutant solid tumors, including colorectal and non-small cell lung cancers. Additionally, Merck announced encouraging outcomes from a clinical trial for zilovertamab vedotin, a treatment for diffuse large B-cell lymphoma, with a 56.3% objective response rate when combined with standard care. Meanwhile, Merck is reportedly in talks to acquire MoonLake Immunotherapeutics for over $3 billion, aiming to strengthen its drug pipeline. Although the initial offer was turned down, discussions may resume, highlighting Merck’s strategy to enhance its portfolio through acquisitions.

Goldman Sachs has maintained a Buy rating on Merck, citing the company’s expansive oncology strategy, which includes over 60 registrational trials. Analysts noted that Merck’s antibody-drug conjugate programs could present significant commercial opportunities by the mid-2030s. BMO Capital also reiterated its Market Perform rating for Merck, acknowledging the company’s robust development pipeline but noting potential short-term challenges. The subcutaneous form of Keytruda is expected to receive FDA approval soon, although its conversion from the intravenous formulation might face hurdles. Merck’s management has expressed a commitment to exploring new therapeutic areas and advancing its oncology pipeline.

This article was generated with the support of AI and reviewed by an editor. For more information see our T&C.

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