RNA therapeutics
Thanassoulis and Anchouche map the Lp(a)-lowering drug pipeline as pelacarsen and olpasiran near their first phase 3 readouts (Curr Atheroscler Rep 2024)
Original title: Lp(a): A Rapidly Evolving Therapeutic Landscape
This review surveys the rapidly developing pipeline of Lp(a)-lowering therapies, framed against Lp(a)'s established causal role in both atherosclerotic coronary disease and aortic stenosis and multiple societies' recommendation to screen every adult at least once, despite no currently approved Lp(a)-specific drug. Pelacarsen and olpasiran, both RNA-based injectable agents that degrade transcribed LPA mRNA to reduce apolipoprotein(a) production, are furthest along, with the earliest phase 3 outcome trial data expected in 2025. Other candidates in earlier-stage development discussed include lepodisiran, zerlasiran, and muvalaplin. The authors conclude that if these agents prove effective in randomised outcome trials, they will meaningfully expand the cardiovascular treatment toolkit by finally addressing a currently unmitigated, genetically determined risk factor.
Original abstract
Purpose Of Review: Elevated lipoprotein(a) (Lp[a]) is a genetically determined cardiovascular risk factor, causally linked to both atherosclerotic coronary artery disease and aortic stenosis. Elevated Lp(a) is widely prevalent, and several cardiovascular societies now recommend performing Lp(a) screening at least once in all adults. However, there are currently no approved drugs aimed specifically at lowering Lp(a). In this review, we describe several promising Lp(a)-lowering therapies in the drug development pipeline and outline what role these may have in future clinical practice.
Recent Findings: Pelacarsen and olpasiran are two novel RNA-based injectable therapies which are being studied in ongoing phase 3 clinical trials, with the earliest of these to be concluded in 2025. These drugs act by degrading transcribed LPA mRNA, which would normally yield the apolipoprotein(a) constituent of Lp(a). Other candidate drugs, such as Lepodisiran, Zerlasiran, and Muvalaplin, are also in early-stage development. While there are presently no Lp(a)-lowering drugs available for routine clinical use, several promising candidates are currently under investigation. If these prove to be effective in randomized clinical trials, they will expand the cardiovascular care armamentarium and will allow clinicians to treat a presently unmitigated cardiovascular risk factor.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.