Lp(a)-lowering therapies (olpasiran / pelacarsen / lepodisiran / zerlasiran / muvalaplin)

What this is

Until 2025 Lp(a) was a non-modifiable risk factor — the entire class is a major shift. Network meta-analyses (Wu Pharmacol Res 2026; Hu Front Cardiovasc Med 2026) confirm olpasiran most potent. Muvalaplin is uniquely oral and would be the first non-injectable in the class. Concomitant PCSK9i further enhances LDL reduction (synergy). For patients with elevated Lp(a) (>50 mg/dL or >125 nmol/L) — roughly 20% of the population — these will likely become standard of care once outcomes are confirmed. Biohacker-relevant: heritable Lp(a) is one of the most undertreated CV risks.

Mechanism

Class targeting LPA gene/apolipoprotein(a) production: siRNAs (olpasiran [Amgen], lepodisiran [Lilly], zerlasiran [Silence]) silence LPA mRNA in hepatocytes via N-acetylgalactosamine conjugation; antisense oligonucleotide pelacarsen (Novartis) blocks LPA mRNA translation; muvalaplin (Lilly) is the first oral small-molecule disrupter of apo(a)-apoB100 covalent bond formation

Dose & route

Olpasiran 75-225 mg SC every 12 weeks; pelacarsen 80 mg SC monthly; lepodisiran SC every 6 months; zerlasiran SC every 6 months; muvalaplin 60-240 mg PO daily

Citations

• https://doi.org/10.1016/j.phrs.2026.108178
• https://doi.org/10.3389/fcvm.2026.1758366
• https://doi.org/10.4070/kcj.2025.0380

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