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Related Experiment Video

Updated: Jan 9, 2026

Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
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Lipoprotein(a) - treatments in development.

Brian Tomlinson1, Chak Fun Law1

  • 1Faculty of Medicine, Macau University of Science & Technology, Macau, China.

Expert Opinion on Pharmacotherapy
|December 6, 2025
PubMed
Summary

Novel therapies like pelacarsen and siRNA agents significantly lower lipoprotein(a) [Lp(a)], a key cardiovascular risk factor. Ongoing trials will determine the clinical benefit of reducing Lp(a) levels.

Keywords:
Pelacarsenlepodisiranmuvalaplinolpasiranzerlasiran

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Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Genetics

Background:

  • Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular diseases, including atheromatous cardiovascular disease and aortic valve stenosis.
  • Current lipid-lowering drugs have minimal impact on elevated Lp(a) levels, necessitating new therapeutic strategies.

Purpose of the Study:

  • To review novel therapies under development for reducing elevated Lp(a) levels.
  • To focus on drugs in advanced stages of clinical development.

Main Methods:

  • PubMed search to identify novel Lp(a)-lowering therapies.
  • Review of drugs in advanced development phases, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and small molecules.

Main Results:

  • N-acetylgalactosamine (GalNAc)-conjugated ASO pelacarsen and siRNA agents (olpasiran, lepodisiran, zerlasiran) demonstrate high safety and efficacy, reducing Lp(a) by 80-100%.
  • Oral small molecule muvalaplin shows up to 65% Lp(a) reduction.
  • Pelacarsen, olpasiran, and lepodisiran are in Phase 3 cardiovascular outcome studies, with results anticipated in 2026. Muvalaplin is also undergoing cardiovascular outcome assessment.

Conclusions:

  • Several novel therapies show significant potential for lowering Lp(a) and may offer cardiovascular benefits.
  • Further research is crucial to establish optimal baseline Lp(a) levels and target reduction percentages for clinical benefit, and to assess potential adverse effects of aggressive Lp(a) lowering.