FDA Approves Enlicitide, the First Oral PCSK9 Inhibitor for High Cholesterol

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Merck announced today that the FDA has approved enlicitide (Lipfendra), marking a major breakthrough as the first-ever oral PCSK9 inhibitor for adults with hypercholesterolemia. The 20 mg once-daily tablet is indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C), commonly known as "bad" cholesterol, including in patients with heterozygous familial hypercholesterolemia (HeFH).

Until now, PCSK9 inhibitors were primarily available through injections. Dean Y. Li, MD, PhD, president of Merck Research Laboratories, described the approval as a "pivotal moment," noting that the drug utilizes novel macrocyclic peptide technology to provide a convenient oral alternative.

The FDA's decision was supported by 2 phase 3 trials in the CORALreef clinical program. In the CORALreef Lipids trial, enlicitide demonstrated a 56% placebo-adjusted reduction in LDL-C at week 24. Results were even higher in the CORALreef HeFH trial, showing a 59% reduction. Ann Marie Navar, MD, a lead author of the studies, highlighted that these "impressive reductions" offer a new pathway for managing a major risk factor for cardiovascular disease.

Enlicitide’s safety profile was generally similar to placebo, though some patients with HeFH reported side effects such as diarrhea (7%) and dizziness (9%). While its ability to lower cholesterol is established, an ongoing trial is currently investigating whether the drug also reduces cardiovascular morbidity and mortality.

REFERENCE

Merck’s Lipfendra (enlicitide) is the first and only once daily oral PCSK9 inhibitor approved by the US FDA to reduce LDL-C in adults with hypercholesterolemia. News release. Merck. July 16, 2026. Accessed July 16, 2026. https://www.merck.com/news/mercks-lipfendra-enlicitide-is-the-first-and-only-once-daily-oral-pcsk9-inhibitor-approved-by-the-u-s-fda-to-reduce-ldl-c-in-adults-with-hypercholesterolemia/