RNA therapeutics
Pelacarsen, olpasiran and SLN360 headline a wave of recent Lp(a)-lowering RNA trials, with outcomes data the next frontier, a review (Curr Opin Lipidol 2022)
Original title: Recent lipoprotein(a) trials
This review summarises recent trials of RNA-based therapies specifically targeting Lp(a), a genetically determined, independent risk factor for cardiovascular disease and calcific aortic stenosis that is minimally affected by conventional lipid-lowering treatments. Antisense oligonucleotides and small interfering RNAs both target the LPA gene, which encodes apolipoprotein(a), the rate-limiting component of hepatic Lp(a) synthesis. Pelacarsen (an ASO) and olpasiran and SLN360 (both siRNAs) have each demonstrated efficacy in dramatically lowering Lp(a) with excellent safety profiles across recent trials. The authors identify cardiovascular outcomes data as the next frontier these trials must address.
Original abstract
Purpose Of Review: Lipoprotein(a) (Lp(a)) is a genetically determined independent risk factor for cardiovascular disease and calcific aortic stenosis; thus, serum levels are minimally affected by conventional treatments for hypercholesterolemia and hypertriglyceridemia. New RNA therapies directly targeting Lp(a) have demonstrated efficacy in decreasing serum levels. Several recent trials have demonstrated efficacy and safety of these RNA therapeutics.
Recent Findings: Single-stranded antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) are two classes of RNA-targeted therapeutics that specifically target the LPA gene, which encodes for apolipoprotein(a), a dominant and rate-limiting component in the hepatic synthesis of Lp(a) particle. Pelacarsen (ASO), olpasiran (siRNA) and SLN360 (siRNA) are novel drugs that have demonstrated efficacy in lowering Lp(a) levels and excellent safety profiles.
Summary: Lp(a) is an independent risk factor for cardiovascular disease. RNA-directed therapies, pelacarsen, olpasiran and SLN360, have shown efficacy in dramatically lowering serum Lp(a) levels. Outcomes data will be the next frontier of Lp(a) trials.
olpasiranpelacarsenRNA therapeutics
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.