RNA therapeutics
Pelacarsen, olpasiran and lepodisiran have shown Lp(a) reductions from -35% to -101% across phase 1/2 trials, review of the therapeutic pipeline finds (Curr Opin Lipidol 2025)
Original title: Therapeutic advances in the Lp(a) battle: what do we know and what are the most awaited novelties in the field?
This review by Jean-Gilles and Gencer surveys the latest advances in Lp(a) treatment, noting that conventional lipid-lowering therapies have no substantial effect on circulating Lp(a), leaving current guidelines focused on managing traditional risk factors instead. New antisense oligonucleotide and small interfering RNA therapies target LPA gene translation directly to reduce apo(a) synthesis and Lp(a) particle formation, with the most advanced candidates, pelacarsen, olpasiran and lepodisiran, showing Lp(a) reductions ranging from -35% to -101% across phase 1 and 2 trials. The authors identify these three RNA-based agents as the most advanced developments in the field, with phase 3 trials expected to conclude between 2025 and 2029, which will determine both their cardiovascular outcome efficacy and address safety concerns around extremely low Lp(a) levels.
Original abstract
Purpose Of Review: To review the latest advances in lipoprotein(a) [Lp(a)] treatment, focusing on the impact of currently available lipid-lowering therapies and highlighting the highly anticipated and most developed RNA-based therapies.
Recent Findings: Lp(a) is a key genetically determined cardiovascular risk modifier linked to myocardial infarction and calcific aortic stenosis development and progression. Conventional lipid-lowering therapies have no substantial effect on circulating Lp(a) levels, leading current guidelines to focus on managing traditional cardiovascular risk factors. New therapies, including antisense oligonucleotides and small interfering RNAs, target Lipoprotein(A) [LPA] gene translation to reduce apo(a) synthesis and Lp(a) particles formation. The most advanced candidates, pelacarsen, olpasiran, and lepodisiran, have shown promising Lp(a) reductions, ranging from -35% to -101% in Phase 1 and 2 trials. Phase 3 studies will clarify their effects on cardiovascular outcomes and address concerns about extremely low Lp(a) levels and safety.
Summary: The RNA-based agents pelacarsen, olpasiran, and lepodisiran represent the most advanced developments in this field. Ongoing Phase 3 trials, expected to be finalized between 2025 and 2029, will be crucial in determining their efficacy in improving cardiovascular outcomes and their safety profiles.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.