On Jul. 16, 2026, Merck announced the U.S. Food and Drug Administration (FDA) has approved LIPFENDRA^® (enlicitide) tablets 20 mg 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 and is the first FDA-approved oral PCSK9 inhibitor shown to lower LDL-C, also known as bad cholesterol.

The approval is based on two Phase 3 trials from the CORALreef clinical program: CORALreef Lipids and CORALreef HeFH. In CORALreef Lipids, LIPFENDRA reduced LDL-C by 56% compared to placebo at week 24. A 60% decrease from baseline in LDL-C was observed with LIPFENDRA when biologically impossible baseline LDL-C values were removed according to revised data handling rules (post-hoc). In CORALreef HeFH, LIPFENDRA reduced LDL-C by 59% at week 24 compared to placebo. Results from these Phase 3 trials showed treatment with LIPFENDRA resulted in reductions across other atherogenic lipoproteins associated with atherosclerotic cardiovascular disease (ASCVD) risk including non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB).

The safety profile of LIPFENDRA in CORALreef Lipids was similar to placebo. In CORALreef HeFH, the most common adverse reactions in adults with HeFH treated with LIPFENDRA that occurred at higher frequencies compared to placebo were diarrhea (LIPFENDRA 7%, placebo 2%) and dizziness (LIPFENDRA 9%, placebo 4%). In both trials, similar proportions of LIPFENDRA-treated patients and placebo-treated patients discontinued treatment because of an adverse reaction.

An ongoing clinical trial is studying the effect of LIPFENDRA on cardiovascular morbidity and mortality. It is not yet known if LIPFENDRA can reduce the risk of cardiovascular morbidity and mortality.

LIPFENDRA is an oral proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor FDA-approved as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). Cardiovascular outcomes trials have demonstrated that reducing LDL-C lowers the risk for major adverse cardiovascular events (MACE) in adults at increased risk, when treated with statins or monoclonal antibody PCSK9 inhibitors as an add-on to statin therapy. LIPFENDRA is the first oral PCSK9 inhibitor approved to reduce LDL-C and is a novel macrocyclic peptide that inhibits the binding of PCSK9 to LDL receptors.