Merck (NYSE: MRK) announced that the U.S. Food and Drug Administration has approved Lipfendra (enlicitide) tablets 20 mg to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH), as an adjunct to diet and exercise.

Lipfendra is a macrocyclic peptide that inhibits the binding of PCSK9 to LDL receptors. According to Merck, it is the first oral PCSK9 inhibitor approved by the FDA to lower LDL-C. Prior approved PCSK9 inhibitors are administered by injection.

The FDA approval is based on two Phase 3 trials. In the CORALreef Lipids trial, which enrolled 2,904 patients, Lipfendra reduced LDL-C by 56% compared to placebo at week 24. In the CORALreef HeFH trial, which enrolled 303 patients with HeFH, Lipfendra reduced LDL-C by 59% compared to placebo at week 24. Both trials used a 2:1 randomization ratio with a once-daily 20 mg oral dose over 52 weeks.

In the CORALreef Lipids trial, adverse reaction frequencies were similar between the Lipfendra and placebo groups. In CORALreef HeFH, the most common adverse reactions occurring at higher rates than placebo were dizziness (9% vs. 4%) and diarrhea (7% vs. 2%). In both trials, similar proportions of patients in each group discontinued treatment due to adverse reactions.

An ongoing cardiovascular outcomes trial, CORALreef Outcomes, has completed enrollment with more than 14,500 participants. Merck stated it is not yet known whether Lipfendra reduces the risk of cardiovascular morbidity and mortality.

According to a statement from the press release, Dr. Dean Y. Li, president of Merck Research Laboratories, said: "This is a pivotal moment as we bring the first U.S. FDA-approved oral PCSK9 inhibitor to adults with high LDL-C, offering patients an important new option."