FDA Approves Merck’s Once-Daily Oral PCSK9 Inhibitor for LDL Reduction

The Food and Drug Administration approved Lipfendra on July 16 for use with diet and exercise to lower LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia. Manufactured by Merck, the drug is the first oral tablet that inhibits the PCSK9 protein, replacing the injections required by earlier drugs in the class that were given every two weeks or monthly.

Two randomized, double-blind, placebo-controlled trials that enrolled 3,207 adults supported the decision.

Participants already received maximally tolerated statin therapy. In one study of patients with atherosclerotic cardiovascular disease or high risk, mean baseline LDL-C of 96 mg/dL fell 56 percent at week 24. In the second study of patients with heterozygous familial hypercholesterolemia, mean baseline LDL-C of 119 mg/dL fell 59 percent at the same point.

The drug also lowered Lp(a) by roughly one quarter. Lipfendra carries a list price of about $300 per month, Reuters reported. Comparable injectable PCSK9 inhibitors list for roughly $500 per month. The American Heart Association estimates that one in four U.S.

Adults has high LDL cholesterol. The drug is intended as an add-on for patients already taking statins who have not reached target LDL levels and is expected to reach pharmacies in the coming weeks, Reuters reported. Side effects occurred at rates similar to placebo across both trials, though diarrhea and dizziness appeared more often with Lipfendra in one study.

Discontinuation rates due to adverse reactions remained comparable between treatment and placebo groups. "Lowering LDL is one of the most effective tools we have in preventive cardiology because it directly targets a major driver of heart disease," said Dr. Jeffrey Berger, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart.

"The oral format could broaden adoption because many patients and physicians are more comfortable with pills than injections," said Dr. William Soliman, founder and CEO of the Accreditation Council for Medical Affairs. Final patient cost will depend on insurance coverage.