Effect on Lipoprotein(a) Oxidized Phospholipids of Lepodisiran, an Extended-Duration siRNA Targeting Lipoprotein(a)

The authors aimed to evaluate the effects of lepodisiran, an extended-duration siRNA targeting lipoprotein(a) [Lp(a)], on levels of oxidized phospholipids (OxPL) associated with apolipoprotein(a) [apo(a)] and apolipoprotein B (apoB) in a phase 2 trial. The study found that lepodisiran significantly reduced OxPL-apo(a) and OxPL-apoB levels, with reductions correlating closely with the decrease in Lp(a), suggesting a potential biological mechanism for its cardiovascular effects. However, the authors caution that these findings do not confirm clinical benefits and highlight the need for further investigation in ongoing trials.