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# FDA OKs Merck's Oral PCSK9 Inhibitor for Lowering Cholesterol
- URL: https://www.fdaweb.com/fda-oks-mercks-oral-pcsk9-inhibitor-for-lowering-cholesterol/
- Published: 2026-07-16T12:00:00.000Z
- Updated: 2026-09-14T13:43:04.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5161471

FDA has approved Merck's Lipfendra (enlicitide) 20 mg tablets as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including patients with heterozygous familial hypercholesterolemia (HeFH), marking the first approval of an oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor in the U.S. for lowering bad cholesterol. The once-daily tablet offers an alternative to injectable PCSK9 inhibitors that have become an important treatment option for patients who require additional LDL cholesterol lowering despite statin therapy.

Lipfendra is described as a novel macrocyclic peptide that lowers LDL cholesterol by binding to PCSK9, preventing the protein from degrading LDL receptors that remove cholesterol from the bloodstream.

The approval was supported by data from two pivotal Phase 3 trials in Merck's CORALreef clinical development program.

In the CORALreef Lipids trial, Merck says Lipfendra reduced LDL cholesterol by a placebo-adjusted 56% at 24 weeks, while patients receiving the drug experienced a 57% reduction from baseline compared with a 3% increase among placebo recipients. A post hoc analysis using revised data handling rules found a 60% reduction from baseline.

In the CORALreef HeFH trial, which enrolled patients with heterozygous familial hypercholesterolemia, the drug reduced LDL cholesterol by 59% versus placebo at 24 weeks, according to the company. Patients receiving LIPFENDRA achieved a 58% reduction from baseline, while LDL cholesterol increased 3% in the placebo group.

Both studies also demonstrated significant reductions in other atherogenic lipoproteins associated with cardiovascular risk, including non-high-density lipoprotein cholesterol and apolipoprotein B.

Although lowering LDL cholesterol is well established as reducing cardiovascular risk, Merck notes that it has not yet been determined whether Lipfendra reduces cardiovascular morbidity or mortality. That question is being evaluated in the ongoing CORALreef Outcomes cardiovascular outcomes trial, which has enrolled more than 14,500 participants.