Lepodisiran advances to phase 3 ACCLAIM-Lp(a) outcomes trial, updated review (Cardiol Rev 2026)

An elevated lipoprotein (a) concentration has been established as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). There is a high prevalence of elevated lipoprotein (a) in the general population, and given the significant burden of ASCVD, researchers have developed novel therapeutic drugs with a direct lipoprotein (a) reducing effect that are currently under investigation. One of these medications is lepodisiran, a small interfering RNA targeting lipoprotein (a). This drug has undergone safety assessment (in Phase 1 and 2 randomized control trials [RCTs]) as well as efficacy assessment (Phase 2 RCT, ALPACA Trial). A phase 3 RCT, ACCLAIM-Lp(a), is currently ongoing with the main purpose of assessing the effect on major cardiovascular events in patients with established ASCVD or at high cardiovascular risk. Herein, we present an updated review on this lipoprotein (a) lowering agent, including the results of the published clinical trials and the design of the ongoing phase 3 clinical trial.