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The FDA on July 15, 2026 approved Lipfendra (enlicitide), Merck's once-daily 20 mg tablet, as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia.
Enlicitide is a macrocyclic peptide that binds PCSK9 directly. PCSK9 drives degradation of the hepatic LDL receptors that clear circulating LDL-C, so blocking it leaves more receptors in place. The biology is the same as the injectable antibodies'; the delivery is what changes.
Approval rests on CORALreef Lipids (NCT05952856), which randomized 2,904 patients 2:1 to enlicitide 20 mg once daily or placebo for 52 weeks. Participants were already on stable lipid-lowering therapy, 97% of them on a statin, with mean baseline LDL-C of 96 mg/dL and mean age 63. At Week 24 the placebo-adjusted reduction in LDL-C was 56%, with non-HDL-C down 53% and ApoB down 50%.
Diarrhea and dizziness were the most common adverse reactions in the HeFH cohort.
Merck describes it as the first and only once-daily oral PCSK9 inhibitor approved in the US.
Clinically, it adds an oral option alongside the injectable PCSK9 therapies, in the labeled population.
Sources: FDA prescribing information; Drugs@FDA, NDA 220848; Merck press release; CORALreef Lipids (NCT05952856); C&EN
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