The U.S. Food and Drug Administration has approved Lipfendra (enlicitide), a once-daily tablet intended to help lower low-density lipoprotein cholesterol, commonly called LDL or “bad” cholesterol.
According to the FDA, Lipfendra is approved for adults with high cholesterol, including adults with heterozygous familial hypercholesterolemia, an inherited condition often abbreviated as HeFH. The medicine is intended to be used alongside diet and exercise.
What makes the approval different
Lipfendra is the first FDA-approved medicine taken by mouth that blocks PCSK9. Other PCSK9 inhibitors have been available, but the FDA described this approval as the first oral option in the class.
PCSK9 is involved in regulating receptors that help remove LDL cholesterol from the bloodstream. Blocking PCSK9 can allow more of those receptors to remain available, helping the body clear additional LDL cholesterol.
The new drug does not replace every existing cholesterol treatment. The FDA noted that available treatment options also include statins and ezetimibe. Decisions about which medicine or combination is appropriate depend on a patient’s diagnosis, cholesterol levels, cardiovascular risk, other medical conditions and tolerance of existing therapy.
Why lowering LDL cholesterol matters
High LDL cholesterol can contribute to fatty plaque accumulating inside artery walls. Over time, that buildup can narrow arteries and restrict blood flow. A plaque rupture may also produce a blood clot, potentially contributing to a heart attack or stroke.
High cholesterol frequently causes no early symptoms. A blood test known as a lipid panel is generally needed to measure cholesterol levels. Diet, physical activity, body weight and genetics can all influence an individual’s cholesterol.
Evidence reviewed by the FDA
The FDA said Lipfendra’s effectiveness and safety were evaluated in two randomized, double-blind, placebo-controlled trials involving a combined 3,207 adults with severe high cholesterol. Participants included people with and without HeFH, and they were already receiving the maximum statin dose they could tolerate.
Both studies measured the percentage change in LDL cholesterol from the beginning of the trial through week 24, compared with placebo.
- In the first trial, participants had a history of atherosclerotic cardiovascular disease or were considered at high risk for it. Their average LDL cholesterol at the start was 96 milligrams per deciliter. The FDA reported an average change of minus 56% in the Lipfendra group compared with placebo.
- The second trial enrolled adults with HeFH. Their average starting LDL cholesterol was 119 milligrams per deciliter. The FDA reported an average change of minus 59% in the Lipfendra group compared with placebo.
These results describe the drug’s effect on LDL cholesterol during the trials. The FDA announcement did not report that these studies were designed to establish whether Lipfendra reduces heart attacks, strokes or cardiovascular deaths.
Safety information reported by the FDA
In the first trial, the overall frequency of adverse reactions was similar in the Lipfendra and placebo groups. In the trial involving adults with HeFH, diarrhea and dizziness occurred more frequently among people receiving Lipfendra than among those receiving placebo.
Across both studies, similar proportions of participants in the treatment and placebo groups stopped treatment because of adverse reactions.
What patients should know
Lipfendra is taken by mouth once each day. Its approval does not mean it is appropriate for every person with high cholesterol, and patients should not start, stop or change cholesterol medication without consulting a qualified health professional.
The FDA granted the application Priority Review and approved the drug for Merck Sharp & Dohme LLC.
Primary source: FDA approval announcement, current as of July 16, 2026.
Medical information notice: This article provides general news and educational information. It is not medical advice and is not a substitute for advice from a physician, pharmacist or other qualified health professional.