A new cholesterol-lowering pill has shown strong results for people with an inherited form of high cholesterol, according to findings from a phase 3 clinical trial.
The study followed adults with familial hypercholesterolemia, a genetic disorder that causes dangerously high levels of LDL, or “bad,” cholesterol. Participants took the oral drug enlicitide once a day for 52 weeks. By week 24, their LDL levels had fallen by an average of 58 percent, researchers reported on November 9 at the American Heart Association meeting in New Orleans and in the Journal of the American Medical Association. In contrast, those taking a placebo saw LDL levels rise slightly — by nearly 3 percent. After a full year, patients on enlicitide maintained an average 55 percent reduction, while LDL levels in the placebo group had increased by about 9 percent.
Enlicitide works by blocking PCSK9, a protein that breaks down LDL receptors in the liver. When PCSK9 is inhibited, more receptors remain active, allowing the liver to remove greater amounts of LDL cholesterol from the bloodstream. Injectable PCSK9 inhibitors already exist and are highly effective, but their uptake has been limited by high costs and access challenges. A pill with the same mechanism could dramatically expand treatment options.
For people with familial hypercholesterolemia, LDL levels are elevated from infancy because their bodies cannot properly clear cholesterol. This leads to a sharply increased risk of heart disease, and even with statins and other treatments, many patients struggle to reach recommended cholesterol targets.
The phase 3 trial focused on the more common form of the condition, inherited from one parent and affecting roughly 1 in 250 people. About 300 adults, all on guideline-recommended statin therapy, participated.
Two additional trials of enlicitide are underway. One will test whether the medication reduces heart attacks and other major cardiovascular events. The other is evaluating whether its cholesterol-lowering effects extend to people without familial hypercholesterolemia. Early results from that study — presented November 8 at the same cardiology meeting — show that enlicitide also significantly lowered LDL levels in people who had experienced, or were at high risk for, a heart attack or stroke.
