Lilly Reports Promising Phase 2 Results for Lepodisiran in Reducing Inherited Cardiovascular Risk Factor

Eli Lilly has announced that its investigational siRNA therapy, lepodisiran, significantly reduced levels of lipoprotein(a), a genetically inherited cardiovascular risk factor, in a Phase 2 study known as ALPACA. Presented at the 2025 American College of Cardiology Scientific Sessions and published in the New England Journal of Medicine, the study showed an average 93.9% reduction in Lp(a) from baseline in adults who received the highest tested dose of 400 mg. Some patients maintained reduced levels for up to 1.5 years.

Lepodisiran was administered in one or two doses, depending on the group, and achieved sustained reductions across all timepoints and doses. Participants receiving two 400 mg doses saw a 94.8% average Lp(a) reduction over the 30 to 360-day period, with levels still 74.2% below baseline at day 540.

The treatment also showed modest reductions in apolipoprotein B levels and was generally well tolerated, with low rates of drug-related adverse events. There were no serious adverse events tied to the drug.

About 20% of Americans have elevated Lp(a), which significantly raises their risk for heart attacks, strokes, and aortic valve disease. Lepodisiran targets the production of apolipoprotein(a), a key component of Lp(a), using RNA interference technology.

The ongoing Phase 3 ACCLAIM-Lp(a) trial will evaluate lepodisiran’s impact on cardiovascular events in adults with elevated Lp(a). Lilly emphasized that the findings address a critical unmet need and reaffirm the company's commitment to advancing genetic medicine.