Current agents reduce Lp(a) by up to 100% in cardiovascular outcome studies, suggesting potential therapies may improve heart health.
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.
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Tomlinson et al. (2025) studied this question.
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