Lepodisiran sustained over 90% Lp(a) reduction and durable effects through a year of biannual dosing in the phase 2 ALPACA trial, narrative review finds (World J Cardiol 2025)

This narrative review covers lepodisiran, an N-acetylgalactosamine-conjugated small interfering RNA that targets hepatic LPA messenger RNA to reduce apolipoprotein(a) production, for elevated lipoprotein(a), a risk factor with limited response to traditional lipid-lowering therapies. Early-phase trials demonstrated sustained Lp(a) reductions above 90% with excellent safety and tolerability, and the phase 2 ALPACA trial confirmed durable effects lasting up to one year with biannual dosing. The authors position lepodisiran favourably against other Lp(a)-lowering agents for its combination of longer dosing intervals, high efficacy and minimal side effects, and note that ongoing phase 3 studies will determine whether these biochemical effects translate into improved cardiovascular outcomes, potentially establishing a new standard in precision ASCVD risk management.