Heterozygous familial hypercholesterolemia is a genetic disorder affecting approximately 1 in 250 people and increasing the risk of premature cardiovascular disease. This disorder results from a gene mutation that reduces the body's ability to remove LDL cholesterol from the blood, leading to a buildup of fatty deposits in the arteries and increasing the risk of atherosclerotic heart disease (ASCVD).
Enlicitide belongs to the PCSK9 inhibitor class of drugs. It works by blocking the PCSK9 protein, which normally breaks down liver receptors responsible for removing LDL cholesterol. By protecting these receptors, Enlicitide enhances the liver's ability to eliminate harmful cholesterol, thus reducing the risk of heart disease.
A randomized, phase 3 trial lasting 52 weeks was conducted, involving 303 adults from 17 countries, all of whom were already receiving cholesterol-lowering treatments such as statins. Participants were divided into two groups: one received Enlicitide at a dose of 20 mg daily, while the other received a placebo. Neither the patients nor the physicians knew which group received which medication.
The results showed that after 24 weeks, LDL levels decreased by an average of 58.2% in Enlicitide users, while placebo users experienced little to no change.
At the end of the trial, Enlicitide patients achieved an average reduction of 55.3% in LDL levels, while LDL levels in the placebo group increased by 8.7%.
The drug also helped lower other cholesterol molecules associated with the risk of coronary artery disease, with levels of lipoprotein B decreasing by 48.2% and levels of lipoprotein A decreasing by 24.7%.
The drug was well-tolerated with few side effects, and the percentage of participants reporting a side effect was similar in both groups: 77.7% for Enlicitide and 76.2% for placebo. The percentage of those who discontinued the drug due to side effects was also low and similar, at 2% for Enlicitide and 3% for placebo.
Clinical trials continue to gather data on whether the cholesterol reduction caused by the drug translates into a reduction in heart attacks and strokes.
The results were published in the journal JAMA.
