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March 6, 2026Cardiology in Review0 citations

Lepodisiran: An Updated Review on a Novel and Emerging Lipoprotein (a) Lowering Agent

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MUManuel Urina-JassirKTKevin TongASAlexander Stanisic

Key Points

  • To review the therapeutic effects of lepodisiran on lipoprotein (a) and its implications for cardiovascular health.
  • Conducted safety assessments in Phase 1 and 2 randomized control trials.
  • Evaluated efficacy in Phase 2 RCT, ALPACA Trial.
  • Described the ongoing Phase 3 RCT, ACCLAIM-Lp(a), focusing on major cardiovascular events.
  • Lepodisiran demonstrated significant lipoprotein (a) lowering in early trials.
  • Ongoing Phase 3 trial aims to further assess cardiovascular outcomes in high-risk populations.

Abstract

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.

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Urina-Jassir et al. (2026) studied this question.

synapsesocial.com/papers/69aa701a531e4c4a9ff5988fhttps://doi.org/10.1097/crd.0000000000001228
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