Lepodisiran — A Long-Duration Small Interfering RNA Targeting Lipoprotein(a)

Elevated lipoprotein(a) concentrations are associated with atherosclerotic cardiovascular disease. The safety and efficacy of lepodisiran, an extended-duration, small interfering RNA targeting hepatic synthesis of lipoprotein(a), are unknown.

We randomly assigned participants in a 1:2:2:2:2 ratio to receive lepodisiran at a dose of 16 mg, 96 mg, or 400 mg at baseline and again at day 180, lepodisiran at a dose of 400 mg at baseline and placebo at day 180, or placebo at baseline and at day 180, all administered by subcutaneous injection. Data from the two groups that received lepodisiran at a dose of 400 mg at baseline were pooled for the primary analysis. The primary end point was the time-averaged percent change from baseline in the serum lipoprotein(a) concentration (lepodisiran difference from placebo [i.e., placebo-adjusted]) during the period from day 60 to day 180.