MSD’s Oral PCSK9 Inhibitor Enlicitide Decanoate Shows Phase III Success

MSD’s oral PCSK9 inhibitor, enlicitide decanoate, has demonstrated robust results in its third Phase III trial for patients with hypercholesterolemia. In the CORALreef Lipids study (NCT05952856), once-daily enlicitide significantly lowered low-density lipoprotein cholesterol (LDL-C) compared to placebo after 24 weeks, meeting the primary endpoint. The therapy also achieved clinically meaningful reductions across key secondary measures, including non-HDL cholesterol, apolipoprotein B, and lipoprotein(a).

Earlier Phase III trials—CORALreef HeFH and CORALreef AddOn—similarly met all primary and secondary endpoints. Designed as a small molecule macrocyclic peptide, enlicitide inhibits PCSK9 interaction with LDL receptors, offering antibody-like efficacy in oral form. If approved, it would be the first oral PCSK9 inhibitor on the market, providing a convenient alternative to injectable therapies. MSD plans to share trial data with regulatory authorities and at upcoming scientific congresses. The oral PCSK9 market is projected to reach $23 billion by 2030, driven by current therapies like Novartis’ Leqvio and Amgen’s Repatha.

08-09-2025