Pelacarsen, olpasiran, lepodisiran and zerlasiran cut Lp(a) by 80 to almost 100%, with phase 3 outcomes readouts possible in 2026, pipeline review finds (Expert Opin Pharmacother 2025)

Original title: Lipoprotein(a) - treatments in development

Expert Opin Pharmacother · 1 December 2025 · 7

Tomlinson B, Law CF

This expert review surveys Lp(a)-lowering therapies in advanced development, identified through a PubMed search focused on the most clinically advanced agents. The GalNAc-conjugated antisense oligonucleotide pelacarsen and the small-interfering RNA agents olpasiran, lepodisiran and zerlasiran have each shown safe and effective Lp(a) reductions of between 80% and almost 100%, with pelacarsen, olpasiran and lepodisiran now being tested in phase 3 cardiovascular outcome studies whose first results may be available in 2026. Muvalaplin, an oral small molecule taken once daily, reduces Lp(a) by up to 65% and is also in a cardiovascular outcome study. The authors identify the open questions that will determine clinical impact: what baseline Lp(a) level warrants treatment, how much lowering is needed for cardiovascular benefit, and whether aggressive Lp(a) lowering carries any adverse effects.

Original abstract

Introduction: Lipoprotein(a) [Lp(a)] is established as an independent risk factor for atheromatous cardiovascular disease and aortic valve stenosis. Currently available lipid-lowering pharmacotherapies have limited effects on elevated levels of Lp(a), and several new therapies are in development to lower Lp(a).

Areas Covered: This article reviews the novel therapies in development to reduce Lp(a) in patients with elevated levels. These were identified by a PubMed search and mainly focus on the drugs that are at an advanced stage of development.

Expert Opinion: The N-acetylgalactosamine (GalNAc)-conjugated antisense oligonucleotide (ASO) pelacarsen and the small-interfering RNA (siRNA) agents olpasiran, lepodisiran, and zerlasiran have all been shown to be safe and effective in lowering Lp(a) levels between 80% and almost 100%. Pelacarsen, olpasiran, and lepodisiran are being tested in phase 3 cardiovascular outcome studies, and the first results may be available in 2026. Muvalaplin is a small molecule given orally once daily and reduces Lp(a) by up to 65%. It is also being assessed in a cardiovascular outcome study. It will be essential to identify what baseline level of Lp(a) is needed, and what degree of Lp(a) lowering is required to produce a cardiovascular benefit and whether aggressive lowering of Lp(a) has any adverse effects.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.