A new cholesterol-lowering drug has delivered promising results in clinical trials for people with heterozygous familial hypercholesterolemia (HeFH)—a common genetic disorder that causes persistently high LDL cholesterol levels.
Understanding HeFH and Its Cardiovascular Risks
HeFH affects approximately 1 in 250 individuals and arises from a gene mutation that weakens the body’s ability to remove LDL cholesterol from the blood. As a result, HeFH patients face a significantly higher risk of premature atherosclerotic cardiovascular disease (ASCVD), where fatty deposits narrow the arteries and restrict blood flow to vital organs.
Enlicitide: A New Generation PCSK9 Inhibitor
As reported by medicalxpress, the investigational drug, Enlicitide, developed by Merck, represents a novel class of PCSK9 inhibitors. It works by binding to PCSK9—an enzyme that usually breaks down liver receptors responsible for clearing LDL cholesterol. By blocking PCSK9, Enlicitide preserves these receptors, enabling the liver to eliminate more LDL cholesterol and ultimately reducing the risk of heart disease.
The findings were published in the journal JAMA.
A Year-Long Global Trial Demonstrates Significant LDL Reduction
Researchers conducted a phase 3, 52-week randomized trial involving 303 adults across 17 countries. All participants had HeFH and were already receiving statins or other lipid-lowering medications. They were randomly assigned to receive either a 20 mg Enlicitide pill once daily or a placebo, with neither doctors nor patients knowing the group assignments.
At 24 weeks, LDL cholesterol levels fell by 58.2% in those taking Enlicitide, while the placebo group showed almost no change. By the end of the 52-week trial, patients on Enlicitide maintained a 55.3% reduction. In contrast, LDL levels in the placebo group increased by 8.7%.
Furthermore, Enlicitide lowered other harmful cholesterol particles:
- Apolipoprotein B decreased by 48.2%
- Lipoprotein (a) fell by 24.7%
Strong Safety Profile and Good Tolerability
The drug demonstrated a favorable safety profile. Adverse effects occurred at similar rates in both groups: 77.7% for Enlicitide and 76.2% for placebo. Discontinuation due to side effects remained low—2% for Enlicitide and 3% for placebo.
“In adults with heterozygous familial hypercholesterolemia, Enlicitide is an effective and well-tolerated treatment for lowering LDL cholesterol,” the researchers wrote.
Next Steps: Broader Trials and Outcome Studies
Ongoing trials aim to determine whether Enlicitide’s powerful cholesterol reductions translate into fewer heart attacks and strokes. Researchers also plan to test the drug in a broader population of high-risk patients beyond those with HeFH.