The FDA has approved Merck’s Lipfendra (enlicitide), an oral PCSK9 inhibitor, as an adjunct to diet and exercise to reduce LDL cholesterol in adults with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH), according to a news release.
The once-daily pill is the first and only oral PCSK9 inhibitor the FDA has approved to lower LDL-C, also known as bad cholesterol.
Enlicitide is a novel macrocyclic peptide that binds to PCSK9 and blocks its interaction with LDL receptors.
Dean Y. Li, M.D., president of Merck Research Laboratories, said in a news release that by harnessing the innovative science of PCSK9 inhibitors and novel macrocyclic peptide technology, Lipfendra was designed to significantly lower LDL-C in the form of a convenient once-daily pill.
Merck brings the first U.S. FDA-approved oral PCSK9 inhibitor to adults with high LDL-C, offering patients an important new option, Dean Y. Li, M.D. noted.
The approval is based on two Phase 3 trials in Merck’s CORALreef program.
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CORALreef Lipids enrolled 2,904 patients with hypercholesterolemia and a history of, or increased risk for, a major atherosclerotic cardiovascular disease (ASCVD) event.
At week 24, Lipfendra reduced LDL-C by 56% compared with placebo, a reduction from baseline of 57% versus a 3% increase for placebo.
In CORALreef HeFH, 303 patients with the inherited condition were randomized 2:1 to Lipfendra or placebo for 52 weeks, and at week 24, Lipfendra reduced LDL-C by 59% versus placebo.
Safety in CORALreef Lipids was similar to placebo, they found.
In CORALreef HeFH, diarrhea and dizziness occurred more often with Lipfendra, but similar proportions of patients in each arm discontinued treatment because of an adverse reaction.
Ann Marie Navar, M.D., a lead author of the CORALreef Lipids study and an associate professor of medicine in the Division of Cardiology at UT Southwestern Medical Center, said high LDL-C is a major risk factor for atherosclerotic cardiovascular disease, which is the leading cause of death globally.
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Lipfendra led to impressive reductions in LDL-C in two Phase 3 trials.
An ongoing trial, CORALreef Outcomes, is evaluating Lipfendra’s effect on cardiovascular morbidity and mortality.
Katherine Wilemon, CEO of the Family Heart Foundation, said timely identification and treatment of risk factors such as LDL-C remains one of the greatest opportunities to manage ASCVD risk.
The broader CORALreef program has enrolled more than 19,000 people with hypercholesterolemia and includes additional studies.
It includes CORALreef Extension, CORALreef Pediatric, and CORALreef Combination studies.
