The FDA approved Lipfendra (enlicitide), the first oral inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (He FH). Previously, PCSK9 inhibitors were available only as injectable therapies. Lipfendra is administered as a once-daily oral tablet.

The efficacy and safety of Lipfendra were evaluated in two randomized, double-blind, placebo-controlled clinical trials involving 3,207 adults receiving maximally tolerated statin therapy. In the first trial, participants with established atherosclerotic cardiovascular disease or high risk had a mean baseline LDL-C of 96 mg/dL; treatment with Lipfendra resulted in an average 56% reduction at Week 24 compared with placebo. In the second trial enrolling adults with He FH (mean baseline LDL-C 119 mg/dL), Lipfendra achieved an average 59% reduction. Adverse reactions were generally similar to placebo, with diarrhea and dizziness more frequent in the He FH trial. Discontinuation rates due to adverse reactions were comparable between groups.

Michael Davis, M.D., Ph.D., Acting Director of the FDA's Center for Drug Evaluation and Research, stated that cardiovascular disease remains the leading cause of death in the United States and elevated LDL cholesterol is one of its most important modifiable risk factors. The approval reflects the FDA's commitment to supporting meaningful advances in patient access.

The approval was granted to Merck Sharp & Dohme LLC under Priority Review and the Commissioner's National Priority Voucher pilot program, intended to accelerate review of therapies addressing national public health priorities.