Expert Opin Pharmacother. 2025 Dec 6. doi: 10.1080/14656566.2025.2601062. Online ahead of print.
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.
PMID:41351386 | DOI:10.1080/14656566.2025.2601062