Lepodisiran: From genetic targeting to cardiovascular promise: A detailed narrative review of the literature

  • World J Cardiol. 2025 Aug 26;17(8):109657. doi: 10.4330/wjc.v17.i8.109657.
Affan Faisal  1 ,  Abdul Basit  1 ,  Abdullah Iftikhar  1 ,  Muneeb Saifullah  1 ,  M Khalil Ur Rehmaan  2 ,  Abdul M Basil  3
Affiliations
  • 1. Department of Medicine, King Edward Medical University, Lahore 54000, Punjab, Pakistan.
  • 2. Department of Medicine, Sialkot Medical College, Sialkot 51040, Punjab, Pakistan.
  • 3. Department of Medicine, Spinghar Medical University, Kabul 1001, Afghanistan. [email protected].
PMID: 40949934 DOI: 10.4330/wjc.v17.i8.109657
Abstract

Elevated lipoprotein(a) [Lp(a)] is a major independent risk factor for atherosclerotic Cardiovascular Disease (ASCVD), with limited response to traditional lipid-lowering therapies. Lepodisiran, a novel N-acetylgalactosamine-conjugated small interfering RNA, targets hepatic LPA message RNA to reduce Apolipoprotein(a) production. Early-phase trials demonstrated > 90% sustained Lp(a) reduction with excellent safety and tolerability. The phase 2 ALPACA trial confirmed durable effects lasting up to one year after biannual dosing. Compared to Other therapies, lepodisiran offers longer duration, high efficacy, and minimal side effects. Ongoing phase 3 studies aim to determine its impact on cardiovascular outcomes, potentially establishing a new standard in precise ASCVD risk management.

Keywords
Atherosclerotic cardiovascular disease; Cardiovascular medicine; Gene targeting; Lepodisiran; Lipid lowering agents.
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