Researchers have found that Enlisted reduces low-density lipoprotein (LDL) “bad cholesterol” by up to 60% in people who have had a previous heart attack or stroke, or who are at high risk of having one.
The new drug may provide an effective alternative to injections of BCSK9 inhibitors to lower harmful cholesterol, according to a preliminary scientific presentation at the 2025 American Heart Association Scientific Sessions, which were held between November 7 and 10, in New Orleans.
The study included 2,912 adults (average age 63 years, 39% of whom were women) who had previously had a heart attack or stroke, or were diagnosed as being at moderate or high risk of having a heart attack or stroke within the next ten years. All participants had LDL levels above recommended levels, despite being on a stable lipid-lowering treatment program for 30 days or more, including moderate- or high-intensity statin therapy (or having a history of statin intolerance).
“This oral medication is poised to be another powerful addition to the treatments we currently have to lower LDL cholesterol and prevent cardiovascular events,” said Dr. Anne-Marie Navarre, MD, Fellow of the American Cardiology Association, associate professor of cardiology at University of Texas Southwestern Medical Center in Dallas, and lead author of the study.
Many patients have difficulty reaching guideline-recommended cholesterol levels, despite currently available treatments, putting them at risk of stroke and/or heart attack.
In the past decade, a new type of drug approved by the US Food and Drug Administration (FDA) has become available to lower harmful cholesterol in people who do not reach recommended levels, despite lifestyle changes and maximum treatment with statin drugs.
These drugs are known as BCSK9 inhibitors, and they contain antibodies that prevent the BCSK9 protein from binding to LDL receptors, in addition to small interfering RNA, which reduces the production of BCSK9.
Inhibiting BCSK9 helps increase the number of LDL receptors available to help remove “bad” cholesterol from the bloodstream. Both types of BCSK9 inhibitors are given by subcutaneous injection only.
Enlisted
In 2021, studies found that enlisted, an oral small-molecule macrocyclic peptide, can also block BCSK9 from binding to LDL receptors, reducing LDL levels in the blood when taken daily.
This study, “Efficacy and Safety of Enlisted, an Oral BCSK-9 Inhibitor, for Lowering Low-Density Lipoprotein Cholesterol in Adults with or at Risk for Coronary Artery Disease: The Phase III CORALRev Lipid Trial,” is a phase III trial in adults to evaluate the safety of enlisted and its ability to lower low-density lipoprotein cholesterol. After 24 weeks of daily treatment, the analysis found that compared to those who took a placebo, participants who took enlisted experienced the following:
Up to a 60% reduction in low-density lipoprotein (LDL) cholesterol, with reductions sustained for 52 weeks, and a 53% reduction in non-high-density lipoprotein (LDL) cholesterol, which is a combination of all types of cholesterol except HLD (good cholesterol).
A 50% reduction in ApoB, a protein that helps transport fats and different types of “bad” cholesterol throughout the body.
A 28% reduction in Lp(a), a different type of lipoprotein structurally similar to LDL, determined by genetics and a risk factor for heart disease, and a similar rate of serious side effects (10% in Enlisted versus 12% in placebo).
“In addition to these significant improvements, compared to placebo, daily administration of Enlisted resulted in nearly similar changes in LDL, low-density lipoprotein, non-HDL, and APOB levels,” Navarre said.