RNA therapeutics
Pelacarsen, olpasiran and SLN360 lower Lp(a) by up to 90%, with pelacarsen phase 3 outcome trial due in 2024, a review (Curr Atheroscler Rep 2022)
Original title: Lp(a): a New Pathway to Target?
This review by Nurmohamed, Kraaijenhof and Stroes summarises genetic and observational evidence positioning Lp(a) as an independent risk factor for atherosclerotic cardiovascular disease and aortic valve stenosis, unaffected by lifestyle intervention and not meaningfully lowered by current lipid-lowering therapies even as LDL cholesterol is now effectively controlled in most patients. Three LPA mRNA-targeted drugs, pelacarsen, olpasiran and SLN360, have shown Lp(a) reductions of up to 90% in clinical development. Pelacarsen is in a phase 3 cardiovascular outcomes trial expected to report in 2024, olpasiran is advancing to phase 3, and SLN360 phase 1 results have recently been published. The authors conclude that, if these trials prove efficacious, Lp(a) will become the next major pathway targeted in cardiovascular risk management.
Original abstract
Purpose Of Review: Over the past decades, genetic and observational evidence has positioned lipoprotein(a) as novel important and independent risk factor for cardiovascular disease (ASCVD) and aortic valve stenosis.
Recent Findings: As Lp(a) levels are determined genetically, lifestyle interventions have no effect on Lp(a)-mediated ASCVD risk. While traditional low-density lipoprotein cholesterol (LDL-C) can now be effectively lowered in the vast majority of patients, current lipid lowering therapies have no clinically relevant Lp(a) lowering effect. There are multiple Lp(a)-directed therapies in clinical development targeting LPA mRNA that have shown to lower Lp(a) plasma levels for up to 90%: pelacarsen, olpasiran, and SLN360. Pelacarsen is currently investigated in a phase 3 cardiovascular outcome trial expected to finish in 2024, while olpasiran is about to proceed to phase 3 and SLN360's phase 1 outcomes were recently published. If proven efficacious, Lp(a) will soon become the next pathway to target in ASCVD risk management.
Dutch researcholpasiranpelacarsenphase 3RNA therapeutics
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.