The U.S. Food and Drug Administration approved Lipfendra (enlicitide) on July 17, 2026, as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C), or “bad” cholesterol, in adults with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH). Lipfendra is the first oral inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9).

PCSK9 inhibitors had previously been available only as injectable therapies. Lipfendra is administered as a once-daily oral tablet and provides an additional treatment option for adults who require further LDL-C reduction despite existing therapies. Other medication classes used to lower LDL-C include statins, ezetimibe and injectable PCSK9 inhibitors.

“This approval provides an additional treatment option for adults with hypercholesterolemia and reflects the FDA’s broader commitment to supporting meaningful advances in patient access and tackling chronic diseases.”

The efficacy and safety of Lipfendra were evaluated in two randomized, double-blind, placebo-controlled clinical trials involving 3,207 adults with hypercholesterolemia, including patients with and without HeFH, who were receiving maximally tolerated statin therapy. In both studies, the primary endpoint was the percent change in LDL-C from baseline to Week 24 compared with placebo.

  • In the first trial, involving adults with established atherosclerotic cardiovascular disease or those at high risk for it, Lipfendra produced an average 56% reduction in LDL-C at Week 24 compared with placebo. Participants had a mean baseline LDL-C of 96 mg/dL.
  • In the second trial, involving adults with HeFH, Lipfendra produced an average 59% reduction in LDL-C at Week 24 compared with placebo. Participants had a mean baseline LDL-C of 119 mg/dL.

In the first trial, adverse reactions occurred at similar frequencies among patients treated with Lipfendra and those receiving placebo. In the second trial, diarrhea and dizziness were the most common adverse reactions occurring more frequently with Lipfendra than placebo. Across both trials, discontinuation rates due to adverse reactions were comparable between the Lipfendra-treated and placebo-recipient groups.

Lipfendra received Priority Review for this indication. The application was also reviewed under the Commissioner’s National Priority Voucher (CNPV) pilot program, which is intended to help accelerate the review of therapies that address national public health priorities. The approval was granted to Merck Sharp & Dohme LLC.