Lp(a)-lowering therapies (olpasiran / pelacarsen / lepodisiran / zerlasiran / muvalaplin)
Metabolic Health · RNA-targeted or small-molecule Lp(a) lowering
Tier A
Bottom line
Read Off Label grades Lp(a)-lowering therapies (olpasiran / pelacarsen / lepodisiran / zerlasiran / muvalaplin) as A (7.9/10) based on strong evidence, very high for lp benefit magnitude, and a low-med-risk safety profile.
Until 2025 Lp(a) was a non-modifiable risk factor — the entire class is a major shift.
Typical use: Olpasiran 75-225 mg SC every 12 weeks; pelacarsen 80 mg SC monthly; lepodisiran SC every 6 months; zerlasiran SC every… — Investigational (pelacarsen Lp(a)HORIZON CVOT readout expected 2026; olpasiran OCEAN(a) Outcomes ongoing).
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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Common questions
- Does Lp(a)-lowering therapies (olpasiran / pelacarsen / lepodisiran / zerlasiran / muvalaplin) work?
- Read Off Label rates the evidence for Lp(a)-lowering therapies (olpasiran / pelacarsen / lepodisiran / zerlasiran / muvalaplin) as Strong and the benefit magnitude as very high for lp, producing an overall grade of A (7.9/10). Until 2025 Lp(a) was a non-modifiable risk factor — the entire class is a major shift.
- Is Lp(a)-lowering therapies (olpasiran / pelacarsen / lepodisiran / zerlasiran / muvalaplin) safe?
- Lp(a)-lowering therapies (olpasiran / pelacarsen / lepodisiran / zerlasiran / muvalaplin) has a low-med risk profile in published human data. Legal status: Investigational (pelacarsen Lp(a)HORIZON CVOT readout expected 2026; olpasiran OCEAN(a) Outcomes ongoing). This is not medical advice — see the disclaimer.
- What is the typical dose for Lp(a)-lowering therapies (olpasiran / pelacarsen / lepodisiran / zerlasiran / muvalaplin)?
- 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
- How does Lp(a)-lowering therapies (olpasiran / pelacarsen / lepodisiran / zerlasiran / muvalaplin) work?
- 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
This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.