Recent trials of a new cholesterol-lowering medication have shown encouraging results for individuals dealing with heterozygous familial hypercholesterolemia (HeFH), a genetic condition that causes elevated levels of LDL cholesterol.
HeFH is relatively common, impacting about 1 in every 250 people. It arises from a mutation in a gene that hinders the body’s ability to eliminate low-density lipoprotein (LDL) cholesterol from the blood. This genetic condition heightens the risk of premature atherosclerotic cardiovascular disease (ASCVD), characterized by a buildup of fatty substances in arteries, which can narrow them and restrict blood flow to essential organs.
The medication, named Enlicitide and produced by Merck, is a novel type of PCSK9 inhibitor. It functions by attaching to PCSK9, a protein in the blood that typically breaks down the liver receptors responsible for clearing LDL cholesterol. By blocking PCSK9, Enlicitide safeguards these receptors, enhancing the liver’s capability to remove LDL cholesterol from the blood, thus potentially lowering heart disease risk.
These findings have been published in the journal JAMA.
Year-long trial
The study was a phase 3, 52-week trial involving 303 adults from 17 countries with HeFH who were already on statins or other cholesterol-lowering treatments. Participants were divided randomly into two groups. One group received a daily dose of 20 mg Enlicitide, while the other took a placebo. Neither the participants nor the medical staff knew who was in which group.
After 24 weeks, those taking Enlicitide experienced an average LDL cholesterol reduction of 58.2%, whereas the placebo group saw almost no change. By the end of the trial at the 52-week mark, Enlicitide users had an average decrease of 55.3% in their LDL cholesterol, while those on the placebo experienced an increase of 8.7% in their levels.
The drug also lowered other cholesterol particles associated with ASCVD risk. Levels of Apolipoprotein B dropped by 48.2%, and Lipoprotein (a) levels went down by 24.7%.
Drug safety
Enlicitide was generally well tolerated, with minimal side effects. The percentage of participants reporting at least one adverse effect was similar in both groups: 77.7% for Enlicitide and 76.2% for the placebo. Additionally, the dropout rate due to side effects was alike, with 2% for Enlicitide and 3% for the placebo.
The researchers concluded, “In adults with heterozygous familial hypercholesterolemia, Enlicitide is an effective and well-tolerated treatment for lowering low-density lipoprotein cholesterol.”
Ongoing studies are investigating whether the significant reduction in cholesterol from Enlicitide translates to a decrease in heart attacks and strokes. The researchers also aim to evaluate this medication in a broader group of high-risk patients beyond those with HeFH.
