The U.S. Food and Drug Administration (FDA) has approved Lipfendra (enlicitide), the first oral inhibitor of proprotein convertase subtilisin/kexin type 9, or PCSK9, to help lower low-density lipoprotein cholesterol, commonly known as "bad" cholesterol, in adults with hypercholesterolemia, according to a news release from the FDA.

The approval allows Lipfendra to be used as an adjunct to diet and exercise to reduce LDL-C in adults with high cholesterol, including those with heterozygous familial hypercholesterolemia, or HeFH, the agency said in the release.

Unlike existing PCSK9 inhibitors, which have only been available as injectable therapies, Lipfendra is taken as a once-daily oral tablet. The FDA said the drug provides an additional treatment option for adults who need further LDL-C reduction despite existing therapies and reflects ongoing advances in chronic cardiovascular disease management.

“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,” said Michael Davis, M.D., Ph.D., acting director of the FDA’s Center for Drug Evaluation and Research, in the release. “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.”

Hypercholesterolemia occurs when there is too much LDL-C in the blood. Excess LDL-C can build up in artery walls over time, contributing to plaque formation that narrows blood vessels and restricts blood flow. If a plaque ruptures, it can trigger a blood clot that increases the risk of heart attack or stroke.

Because high cholesterol typically causes no symptoms, many people are unaware they have the condition until routine blood testing detects it. Factors that can contribute to elevated cholesterol levels include diet, physical inactivity, excess body weight and inherited genetic conditions, the agency said.

Several classes of medications are currently used to lower LDL-C, including statins, ezetimibe and injectable PCSK9 inhibitors. Lipfendra becomes the first oral therapy in the PCSK9 inhibitor class.

The FDA evaluated the drug’s safety and effectiveness through two randomized, double-blind, placebo-controlled clinical trials involving 3,207 adults with hypercholesterolemia, including patients with and without HeFH. All participants were receiving maximally tolerated statin therapy. The primary endpoint in both studies measured the percent change in LDL-C from baseline to Week 24 compared with placebo, the release said.

In the first trial, which included adults with established atherosclerotic cardiovascular disease, or ASCVD, as well as those at high risk for ASCVD, participants had a mean baseline LDL-C level of 96 mg/dL. Patients treated with Lipfendra achieved an average 56% reduction in LDL-C at Week 24 compared with placebo.

In the second trial, which enrolled adults with HeFH, participants had a mean baseline LDL-C level of 119 mg/dL. Patients receiving Lipfendra experienced an average 59% reduction in LDL-C at Week 24 compared with placebo.

The FDA reported that adverse reaction rates in the first trial were similar between patients receiving Lipfendra and those receiving placebo. In the second trial, diarrhea and dizziness were the most common adverse reactions reported more frequently among Lipfendra-treated patients than those receiving placebo. Across both studies, discontinuation rates due to adverse reactions were comparable between the treatment and placebo groups.

Lipfendra received Priority Review for the indication. The application was also reviewed through the Commissioner’s National Priority Voucher pilot program, which is designed to help accelerate reviews of therapies that address national public health priorities.

The approval was granted to Merck Sharp & Dohme LLC, according to the release.