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Emerging therapies to lower lipoprotein(a) and the current clinical trials landscape: RNA-therapeutics and beyond.

Created on 29 Jul 2026

Authors

Sawye Raygani, Michael J Wilkinson

Published in

Journal of clinical lipidology. Jul 03, 2026. Epub Jul 03, 2026.

Abstract

Lipoprotein(a) [Lp(a)] is a genetically determined, independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease. Currently, the only Food and Drug Administration-approved treatment for Lp(a) reduction is lipoprotein apheresis. Emerging targeted pharmacotherapies have shown significant reductions in Lp(a) levels in phase 2 trials. Phase 3 trials are currently underway to assess whether those significant Lp(a) reductions reduce the risk of major adverse cardiovascular events (MACE).
PubMed, ClinicalTrials.gov. ABSTRACT OF FINDINGS: Certain lipid-lowering pharmacotherapies, such as proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibodies and small-interfering RNA therapeutics, have shown modest reductions in Lp(a) in conjunction with their primary low-density lipoprotein cholesterol-lowering effect. Lp(a)-targeted pharmacotherapies, such as antisense oligonucleotides, small interfering RNA therapeutics, and small molecule inhibitors, significantly reduce Lp(a) levels in phase 2 clinical trials.
The Lp(a) clinical trials landscape now includes multiple therapies in development, including several in phase 3 CV outcomes trials. Results are highly anticipated and will reveal whether significant Lp(a) reduction prevents MACEs in various groups of patients with different forms of ASCVD or CV risk factors, different degrees of baseline Lp(a) elevation, and in the setting of different absolute and percentage reductions in Lp(a).

PMID:
42521529
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.

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