Lipfendra, a once-daily pill, reduced LDL cholesterol by up to 59% in late-stage trials, rivaling existing injectable treatments
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Merck $MRK won U.S. Food and Drug Administration approval on Thursday for Lipfendra (enlicitide), making it the first oral PCSK9 inhibitor cleared by the agency to lower LDL cholesterol in adults with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia.
Lipfendra, taken once daily as a 20 mg tablet, works by blocking the PCSK9 protein, which plays a role in regulating cholesterol levels, the company said. Existing PCSK9 inhibitors — such as Amgen $AMGN's Repatha and Regeneron $REGN and Sanofi's Praluent — are administered by injection, according to CNBC.
The FDA based its approval on two Phase 3 trials from Merck's CORALreef clinical program. In the CORALreef Lipids trial, which enrolled 2,904 patients, Lipfendra reduced LDL cholesterol by 56% compared to placebo at week 24. In the CORALreef HeFH trial, which enrolled 303 patients with familial hypercholesterolemia, the drug reduced LDL cholesterol by 59% versus placebo at the same timepoint, the company said. Both trials also showed reductions in non-HDL cholesterol and apolipoprotein B, additional markers associated with cardiovascular disease risk.
The drug's safety profile in the CORALreef Lipids trial was similar to placebo, Merck said. In the HeFH trial, the most common adverse reactions occurring at higher rates than placebo were dizziness, at 9% for Lipfendra versus 4% for placebo, and diarrhea, at 7% versus 2%. In both trials, similar proportions of patients in the treatment and placebo groups stopped taking the drug due to adverse reactions.
"High LDL-C is a major risk factor for atherosclerotic cardiovascular disease, which is the leading cause of death globally," said Dr. Ann Marie Navar, a lead author of the CORALreef Lipids study and associate professor of medicine in the Division of Cardiology at UT Southwestern Medical Center, in a statement. About one in four adults in the U.S. have high LDL cholesterol, according to CNN.
An ongoing cardiovascular outcomes trial, CORALreef Outcomes, which has completed enrollment with more than 14,500 participants, is studying whether Lipfendra reduces cardiovascular morbidity and mortality, the company said. That question remains unanswered.
Lipfendra was granted the FDA commissioner's National Priority Voucher, a program that accelerates regulatory review for drugs deemed essential to public health, according to CNBC. The timing is significant for Merck, which faces a major revenue challenge as Keytruda, its flagship cancer immunotherapy, is set to encounter biosimilar competition after its patent protections begin expiring in 2028. Merck reported first-quarter Keytruda sales of $8.03 billion, up 12% year over year, as the drug continues to anchor the company's revenue.
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