The U.S. Food and Drug Administration on Thursday approved Lipfendra, the first once-daily pill designed to lower cholesterol through a mechanism that previously required injections, offering a potentially transformative option for millions of Americans with dangerously high cholesterol levels that remain uncontrolled despite statin therapy.
Manufactured by Merck, Lipfendra is known generically as enlicitide and represents a breakthrough in how doctors can address a leading risk factor for heart disease and stroke. The drug is intended for adults with hypercholesterolemia, including those with an inherited form of the disease called heterozygous familial hypercholesterolemia, a genetic condition that causes extremely elevated cholesterol levels from birth.
The medication works by blocking a protein called PCSK9 that limits the body’s ability to clear low-density lipoprotein, or LDL cholesterol, from the bloodstream. Until now, drugs targeting PCSK9 have only been available as injections, including Amgen’s Repatha and Regeneron and Sanofi’s Praluent, which cost roughly $500 to $600 per month.
Lipfendra is taken as a 20-milligram tablet once daily and priced at $315 for a 30-day supply, significantly lower than existing injectable alternatives. Merck said the drug should reach pharmacies within a few weeks.
The approval rested on two late-stage clinical trials from Merck’s CORALreef program, which together enrolled 3,207 adults already taking the highest tolerable dose of statins. In one trial involving patients with a history of atherosclerotic cardiovascular disease or at high risk for it, Lipfendra reduced LDL cholesterol by 56 percent from a baseline average of 96 milligrams per deciliter after 24 weeks, compared with placebo. In a second trial focused exclusively on patients with the inherited form of high cholesterol, the drug achieved a 59 percent reduction from a baseline average of 119 milligrams per deciliter.
Heart disease remains the nation’s leading cause of death, and elevated LDL cholesterol is a primary risk factor for heart attacks and strokes. Mainstream medical guidelines now recommend that people at above-average risk for cardiovascular events achieve LDL levels below 70, and those at high risk—such as heart attack survivors—should get their levels below 55.
The drug carries advantages beyond convenience and cost. Analyses indicated that Lipfendra has no contraindications or warnings for allergic reactions, unlike its injectable competitors. In trials of patients without inherited high cholesterol, the safety profile was similar to placebo. In the inherited cholesterol trial, the most frequently reported adverse effects were diarrhea and dizziness, conditions that occurred at slightly higher rates than with placebo, though similar proportions of patients in both treatment and placebo groups discontinued therapy due to side effects.
Dr. David Maron, a preventive cardiologist at Stanford University in California, said that the pricing advantage compared with injectable PCSK9 inhibitors “would make a big difference.” Despite a decade of approved injectable options, an estimated 70 percent or more of eligible high-risk cardiovascular disease patients remain undertreated, driven by injection aversion, insurance approval burdens, and limited access to specialists in primary care settings. Merck officials indicated they want lowering cholesterol with the drug to feel as routine as taking a statin and that primary care doctors, not just cardiologists, can prescribe it.
About one in four American adults have high LDL cholesterol according to the American Heart Association. While oral statins represent the first-line treatment for elevated cholesterol, they do not lower levels enough for many high-risk patients. Lipfendra offers an option for those whose cholesterol remains dangerously elevated despite maximum statin therapy.
Merck said that Lipfendra’s formal approval represents one aspect of the company’s broader efforts to diversify its pipeline beyond its blockbuster cancer drug Keytruda, which faces generic competition starting in 2028. The FDA’s approval also reflected the agency’s commitment to expedited review for promising medications serving significant public health needs. The approval positions Merck competitively within the cholesterol treatment landscape and signals potential expansion of PCSK9 inhibitor access among the large population of patients who could benefit from more aggressive cholesterol management.