Merck has announced that the US Food and Drug Administration (FDA) has approved LIPFENDRA® (enlicitide) 20 mg, making it the first and only once-daily oral PCSK9 inhibitor for lowering low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH). The approval marks the first oral alternative to injectable PCSK9 inhibitors.
LIPFENDRA is approved as an adjunct to diet, exercise and maximally tolerated lipid-lowering therapy for adults who require additional LDL-C reduction. Until now, PCSK9 inhibitors were available only as injectable therapies, creating a new oral treatment option for patients needing intensive cholesterol lowering.
The approval is based on results from the Phase III CORALreef Lipids and CORALreef HeFH trials involving 3,207 adults with severe hypercholesterolemia. At 24 weeks, patients receiving LIPFENDRA achieved placebo-adjusted reductions in LDL cholesterol of 56% in patients with established or high-risk atherosclerotic cardiovascular disease and 59% in patients with heterozygous familial hypercholesterolemia.
LIPFENDRA (enlicitide) is a novel macrocyclic peptide that blocks the PCSK9 protein, allowing more LDL receptors to remain active and remove "bad" cholesterol from the bloodstream. The medicine is taken as a 20 mg tablet once daily.
Clinical studies showed that the overall safety profile of LIPFENDRA was similar to placebo. The most commonly reported adverse events in patients with HeFH were diarrhea and dizziness, while treatment discontinuation due to adverse events was low and comparable between treatment groups.
While the approval was based on its proven ability to significantly reduce LDL cholesterol, Merck is continuing the CORALreef Outcomes study to evaluate whether LIPFENDRA also lowers the risk of major cardiovascular events such as heart attack and stroke.
The approval provides physicians and patients with the first oral option in the PCSK9 inhibitor class, potentially improving treatment convenience and adherence for individuals who require additional LDL cholesterol reduction beyond standard therapies.
