Merck announced that the FDA has approved LIPFENDRA (enlicitide) 20 mg tablets as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). LIPFENDRA is a novel macrocyclic peptide that binds to PCSK9 and inhibits its interaction with LDL receptors, and is the first FDA-approved oral PCSK9 inhibitor for LDL-C lowering.
The approval is based on results from two Phase 3 studies in the CORALreef program: CORALreef Lipids and CORALreef HeFH. In CORALreef Lipids, LIPFENDRA achieved a placebo‑adjusted LDL-C reduction of 56% at week 24. When biologically implausible baseline LDL-C values were excluded in a post‑hoc analysis, a 60% decrease from baseline was observed. In CORALreef HeFH, LIPFENDRA reduced LDL-C by 59% compared with placebo at week 24.
Across both trials, treatment with LIPFENDRA also lowered other atherogenic lipoproteins associated with atherosclerotic cardiovascular disease risk, including non‑HDL cholesterol and apolipoprotein B. The safety profile in CORALreef Lipids was similar to placebo. In CORALreef HeFH, adverse reactions that occurred more frequently with LIPFENDRA than placebo included diarrhea (7% vs 2%) and dizziness (9% vs 4%), with similar discontinuation rates due to adverse events in both groups.
An ongoing clinical trial is evaluating the effect of LIPFENDRA on cardiovascular morbidity and mortality; it is not yet known whether use of LIPFENDRA reduces cardiovascular risk.
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