Merck, known as MSD outside the United States and Canada, has announced that the U.S. Food and Drug Administration (FDA) has approved LIPFENDRA (enlicitide) 20 mg tablets for adults with high cholesterol. The medicine is approved to be used along with a healthy diet and regular exercise to reduce low-density lipoprotein cholesterol (LDL-C), commonly known as “bad cholesterol,” in adults with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH).
The approval marks an important milestone in cholesterol treatment, as LIPFENDRA is the first FDA-approved oral PCSK9 inhibitor. Until now, PCSK9 inhibitors, which are highly effective at lowering LDL cholesterol, have only been available as injectable medicines. LIPFENDRA offers patients the convenience of a once-daily tablet.
LDL cholesterol is a major risk factor for atherosclerotic cardiovascular disease (ASCVD), a condition in which fatty deposits build up inside arteries. ASCVD can lead to serious health problems, including heart attacks and strokes, and remains the leading cause of death worldwide.
Dr. Dean Y. Li, President of Merck Research Laboratories, said the approval reflects the company’s work in developing a new treatment based on PCSK9 inhibition and macrocyclic peptide technology. He said LIPFENDRA was designed to significantly lower LDL cholesterol in the form of a convenient daily pill, providing patients with an important new treatment option.
The FDA’s decision was supported by results from two Phase 3 clinical trials in the CORALreef development program: CORALreef Lipids and CORALreef HeFH.
In the CORALreef Lipids study, patients treated with LIPFENDRA experienced a 56% reduction in LDL cholesterol after 24 weeks compared with placebo. A later analysis that excluded biologically impossible baseline LDL cholesterol values showed an even greater reduction of 60% from baseline.
The second Phase 3 study, CORALreef HeFH, focused on patients with heterozygous familial hypercholesterolemia, an inherited condition that causes very high cholesterol levels from birth. In this trial, LIPFENDRA reduced LDL cholesterol by 59% compared with placebo after 24 weeks.
Researchers also found that LIPFENDRA significantly reduced other harmful blood fats linked to cardiovascular disease. Patients receiving the treatment experienced meaningful reductions in non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB), both of which are important markers associated with heart disease risk.
Dr. Ann Marie Navar, Associate Professor of Medicine in the Division of Cardiology at UT Southwestern Medical Center and a lead author of the CORALreef Lipids study, said high LDL cholesterol remains one of the biggest risk factors for cardiovascular disease. She noted that the Phase 3 studies showed impressive reductions in LDL cholesterol and highlighted that patients now have access to the first oral PCSK9 inhibitor for cholesterol lowering.
The safety results were generally favorable. In the CORALreef Lipids trial, the safety profile of LIPFENDRA was similar to that of placebo. In the CORALreef HeFH study, the most commonly reported side effects were diarrhea, occurring in 7% of patients compared with 2% in the placebo group, and dizziness, reported in 9% of patients compared with 4% receiving placebo. Similar numbers of patients in both treatment and placebo groups stopped treatment because of side effects.
Merck also noted that an ongoing clinical trial is evaluating whether LIPFENDRA can reduce the risk of heart attacks, strokes, and other cardiovascular events. While the medicine has clearly demonstrated its ability to lower LDL cholesterol, it has not yet been proven to reduce cardiovascular illness or death.
Katherine Wilemon, Chief Executive Officer of the Family Heart Foundation, welcomed the approval, saying that early identification and effective treatment of high LDL cholesterol are essential to lowering the risk of cardiovascular disease. She added that the availability of a new oral PCSK9 inhibitor provides another valuable option for adults who need additional cholesterol reduction.
With the FDA approval of LIPFENDRA, healthcare providers now have a new once-daily oral treatment that could make advanced cholesterol-lowering therapy more accessible and convenient for many patients living with high LDL cholesterol.