Merck's Enlicitide Fails to Impress in Hypercholesterolemia Study

Merck has announced that its experimental drug, Enlicitide, met primary and secondary endpoints in a study for hypercholesterolemia. The drug aims to reduce levels of "bad" LDL cholesterol in the blood. Merck has been developing Enlicitide to treat high cholesterol, a major risk factor for heart disease.

Merck (NYSE: MRK) has announced positive topline results from the Phase 3 CORALreef Lipids trial, showcasing the efficacy of its investigational oral PCSK9 inhibitor, enlicitide decanoate, in reducing low-density lipoprotein cholesterol (LDL-C) levels in adults with hypercholesterolemia. The study, which enrolled over 1,000 participants, met all primary and key secondary endpoints, highlighting enlicitide's potential to address a significant unmet medical need.

Key Findings

The primary endpoint of the study, a statistically significant and clinically meaningful reduction in LDL-C compared to placebo at Week 24, was achieved. Enlicitide demonstrated statistically and clinically significant reductions in LDL-C, non-HDL-C, apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)] at Week 24 compared to placebo. The drug also showed a favorable safety profile, with comparable rates of adverse events and discontinuations due to adverse events between treatment groups.

Clinical Implications

Hypercholesterolemia, a major risk factor for atherosclerotic cardiovascular disease (ASCVD), affects approximately 86 million adults in the U.S. [1]. Enlicitide's ability to lower LDL-C levels could help more patients achieve guideline-recommended lipid goals, ultimately reducing ASCVD risk. Merck plans to share these results with regulatory authorities worldwide and present the data at a future scientific congress.

Market Potential

The global PCSK9 inhibitor market size was valued at USD 14.2 billion in 2020 and is expected to grow at a CAGR of 12.8% from 2021 to 2028 [2]. Enlicitide's oral formulation, if approved, could disrupt the market by offering a convenient, pill-based alternative to injectable PCSK9 inhibitors. This could expand the patient population eligible for treatment, as some patients may prefer oral medications over injections.

Regulatory and Commercial Outlook

Merck's focus on cardiovascular disease aligns with its long history of developing treatments for this condition. The company's commitment to advancing research in this area is evident in the comprehensive CORALreef Clinical Trial program, which includes the large cardiovascular outcomes trial, CORALreef Outcomes, with over 14,500 participants. The successful completion of the CORALreef Lipids trial positions enlicitide as a promising candidate for regulatory approval and commercialization.

Forward-Looking Statements

As with any investigational drug, there are risks and uncertainties associated with enlicitide's development and commercialization. Merck's forward-looking statements emphasize the potential risks and uncertainties, including regulatory approval, market competition, and the impact of pharmaceutical industry regulation and health care legislation [3].

References

[1] Merck. (2025). Merck's Investigational Oral PCSK9 Inhibitor Enlicitide Decanoate Meets Primary and Key Secondary Endpoints in Adults with Hypercholesterolemia in Pivotal CORALreef Lipids Study. Retrieved from https://www.merck.com/news/mercks-investigational-oral-pcsk9-inhibitor-enlicitide-decanoate-met-all-primary-and-key-secondary-endpoints-in-adults-with-hypercholesterolemia-in-pivotal-coralreef-lipids-study/
[2] MarketWatch. (2021). PCSK9 Inhibitor Market Size, Share & Trends Analysis Report By Product (Evolocumab, Alirocumab, Bococizumab), By Route of Administration (Subcutaneous, Intravenous), By End Use (Hospital, Ambulatory Surgical Center, Others), By Region, And Segment Forecasts, 2021 - 2028. Retrieved from https://www.marketwatch.com/press-release/pcsk9-inhibitor-market-size-share-trends-analysis-report-by-product-evolocumab-alirocumab-bococizumab-by-route-of-administration-subcutaneous-intravenous-by-end-use-hospital-ambulatory-surgical-center-others-by-region-and-segment-forecasts-2021-2028-2021-09-02
[3] Merck & Co., Inc. (2024). Annual Report on Form 10-K for the year ended December 31, 2024. Retrieved from https://www.sec.gov/Archives/edgar/data/93232/0000932324-24-000002-index.htm