The US Food and Drug Administration has approved enlicitide (LIPFENDRA) as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia, according to a press release from Merck.
The company said enlicitide is the first FDA-approved oral proprotein convertase subtilisin/kexin type 9 inhibitor. The 20-mg tablet is taken once daily. Enlicitide is a macrocyclic peptide that binds PCSK9 and inhibits its interaction with LDL receptors.
The approval was supported by the randomized, double-blind, placebo-controlled phase 3 CORALreef Lipids and CORALreef HeFH trials. Both evaluated enlicitide in adults who required additional LDL-C reduction despite stable lipid-lowering treatment.
In CORALreef Lipids, Merck reported that enlicitide produced a 56% placebo-adjusted reduction in LDL-C at week 24. The trial also found reductions in non–high-density lipoprotein cholesterol and apolipoprotein B compared with placebo.
In a post hoc analysis that removed LDL-C values of 0 or less under revised data-handling rules, the company reported a 60% reduction from baseline with enlicitide. This analysis was separate from the trial’s primary efficacy result.
In CORALreef HeFH, enlicitide produced a 59% placebo-adjusted reduction in LDL-C at week 24, according to the release. Reductions in non–high-density lipoprotein cholesterol and apolipoprotein B were also reported.
Merck said adverse-reaction frequencies in CORALreef Lipids were similar between the enlicitide and placebo groups, as were discontinuations resulting from adverse reactions. In CORALreef HeFH, diarrhea occurred in 7% of enlicitide-treated patients and 2% of placebo-treated patients, while dizziness occurred in 9% and 4%, respectively. Discontinuation rates resulting from adverse reactions were similar between groups.
An ongoing cardiovascular outcomes trial is evaluating the effect of enlicitide on cardiovascular morbidity and mortality. Merck stated that it is not yet known whether the treatment reduces the risk of cardiovascular morbidity or mortality.
Source: Merck