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| Other names | MK-0616 |
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| Formula | C92H129FN14O17 |
| Molar mass | 1722.123 g·mol−1 |
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Enlicitide decanoate (previously known as MK-0616 [1] ) is an orally available macrocyclic peptide investigational drug that is being evaluated for the treatment of hypercholesterolaemia. It is a PCSK9 inhibitor. [2] [3] A 2025 review paper of cholesterol-lowering drugs with PCSK9 and other biomolecules as a target, states that "[enlicitide] promises to be a blockbuster cholesterol-lowering drug as it exhibits a high degree of efficiency in clinical trials and of potential for applications in individuals where statins and dietary adjustments are not sufficient." [4] The drug is being developed by Merck, which expects to apply for FDA approval in early 2026. [5]
Enlicitide decanoate interacts with the LDL receptor binding domain of PCSK9 and inhibits its interaction with the receptor with an IC50 of 2.5 ±0.1 nM. [6]
A double-blind, placebo-controlled Phase I clinical trial demonstrated that oral administration of the drug in 60 healthy males at doses of 10, 35, 100, 200, and 300 mg reduced free plasma levels of PCSK9 by more than 93%. [6] In a separate Phase I study with statin-treated participants, daily doses of 10 and 20 mg reduced LDL levels at 14 days by 58.2 and 60.5%, respectively. [6]
A Phase IIB study of eight weeks evaluated efficacy and safety in patients with hypercholesterolemia. Daily oral doses of 6, 12, 18, or 30 mg reduced LDL by 41.2, 55.7, 59.1, and 60.9% at the end point. Essentially complete efficacy was reached after two weeks. Adverse events were comparable to placebo at all doses throughout the study period. [6]
On 10 August 2023 Merck launched the Phase III CORALreef Lipids clinical trial to evaluate the efficacy and safety of MK-0616 in adults with hypercholesterolemia. [7] [8] The study included 2,912 participants and was completed on 28 July 2025 with results announced on 2 September 2025. [9] [5]
