Novel Lipoprotein (a) Therapies: A Comprehensive Review.
U, E., O, U., R, S., & A, K. (2026). Novel Lipoprotein (a) Therapies: A Comprehensive Review.. Current atherosclerosis reports. https://doi.org/10.1007/s11883-026-01453-9
U E, O U, R S, A K. Novel Lipoprotein (a) Therapies: A Comprehensive Review.. Current atherosclerosis reports. 2026; doi: 10.1007/s11883-026-01453-9
U E, O U, R S, et al. Novel Lipoprotein (a) Therapies: A Comprehensive Review.[J]. Current atherosclerosis reports. 2026. DOI: 10.1007/s11883-026-01453-9.
@article{u2026,
author = {Ebubechukwu U and Ugoala O and Shahid R and Kulkarni A},
title = {Novel Lipoprotein (a) Therapies: A Comprehensive Review.},
journal = {Current atherosclerosis reports},
year = {2026},
doi = {10.1007/s11883-026-01453-9},
note = {PMID: 42593611},
}
TY - JOUR AU - Ebubechukwu U AU - Ugoala O AU - Shahid R AU - Kulkarni A TI - Novel Lipoprotein (a) Therapies: A Comprehensive Review. T2 - Current atherosclerosis reports PY - 2026 DO - 10.1007/s11883-026-01453-9 AN - PMID:42593611 ER -
PURPOSE OF REVIEW: Lipoprotein(a) [Lp(a)] is a genetically determined, independent risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Plasma Lp(a) levels are 70-90% heritable, largely unresponsive to lifestyle changes, and poorly controlled with typical lipid-lowering drugs such as statins and PCSK9 inhibitors. The development of powerful RNA-based therapies offers a new chance to specifically target and significantly lower Lp(a). We examined available phase 1-3 trial data, regulatory updates, and trial registries up to mid-2026 to provide an overview of the current pipeline, ongoing cardiovascular outcomes trials (CVOTs), and new mechanistic and genomic methods. RECENT FINDINGS: Five agents across three mechanisms have reached late-stage development. Pelacarsen, a GalNAc-conjugated antisense oligonucleotide (ASO), reduces Lp(a) by about 80% via hepatic apo(a) mRNA reduction and is the subject of the phase 3 Lp(a) HORIZON trial, with results due in late 2026. Three small interfering RNA (siRNA) drugs, olpasiran (> 95% reduction, OCEAN(a)-Outcomes), lepodisiran (93.9% reduction lasting over 12 months after one dose, ACCLAIM-Lp(a)), and zerlasiran (96.4% reduction), allow quarterly or possibly yearly dosing. Muvalaplin, the first oral small-molecule Lp(a) inhibitor, interferes with apo(a)-ApoB particle formation and reduces intact Lp(a) by up to 85.8% in phase 2 KRAKEN trials; its phase 3 CVOT (MOVE-Lp(a)) is underway. Additionally, CRISPR/Cas9-based liver gene editing targeting the LPA gene (CTX320) has entered phase 1 studies. All agents have shown good safety so far. The Lp(a) treatment landscape has moved from basic science to an active late-stage clinical pipeline. Positive outcomes from these CVOTs could lead to regulatory approvals and guideline updates affecting hundreds of millions of high-risk patients globally. Recent guidelines now recommend universal Lp(a) measurement, in anticipation of more effective therapies becoming available within the next 1 to 2 years.