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Lp(a): A Rapidly Evolving Therapeutic Landscape

Khalil Anchouche1,2, George Thanassoulis3,4

  • 1McGill University Health Centre and Research Institute, Montréal, Québec, Canada.

Current Atherosclerosis Reports
|November 22, 2024
PubMed

Insights

Novel therapies targeting elevated lipoprotein(a) (Lp[a]) are in development. These promising treatments aim to lower Lp[a] levels, addressing a significant, unmitigated cardiovascular risk factor.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Genetics

Background:

  • Elevated lipoprotein(a) (Lp[a]) is a genetically determined risk factor for atherosclerotic coronary artery disease and aortic stenosis.
  • Lp[a] is prevalent, prompting recommendations for universal adult screening.
  • Currently, no specific Lp[a]-lowering drugs are approved for clinical use.

Purpose of the Study:

  • To review emerging Lp[a]-lowering therapies in the drug development pipeline.
  • To discuss the potential future clinical applications of these novel treatments.

Main Methods:

  • Review of ongoing phase 3 clinical trials for novel Lp[a]-lowering therapies.
  • Description of RNA-based therapies targeting LPA mRNA degradation.
  • Overview of early-stage drug development candidates.

Main Results:

  • Pelacarsen and olpasiran are RNA-based therapies in phase 3 trials, degrading LPA mRNA.
  • Other candidates like Lepodisiran, Zerlasiran, and Muvalaplin are in early development.
  • No Lp[a]-lowering drugs are currently approved, but promising candidates are under investigation.

Conclusions:

  • Novel RNA-based therapies show promise for lowering lipoprotein(a).
  • Successful clinical trials could provide the first treatments for this cardiovascular risk factor.
  • These therapies may significantly expand cardiovascular care options.
Abstract

Keywords:
Antisense oligonucleotides (ASO)Aortic stenosis (AS)Coronary artery disease (CAD)Lipoprotein(a) (Lp[a])Small interfering RNA (siRNA)

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