Faisal A, Basit A, Iftikhar A, Saifullah M, Rehmaan MKU, Basil AM. Lepodisiran: From genetic targeting to cardiovascular promise: A detailed narrative review of the literature. World J Cardiol 2025; 17(8): 109657 [DOI: 10.4330/wjc.v17.i8.109657]
Corresponding Author of This Article
Abdul M Basil, MD, Doctor, Department of Medicine, Spinghar Medical University, 4th Alley, Char Rahe Qambar Kabul, Kabul 1001, Afghanistan. abdulmaboodbasil@outlook.com
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Cardiol. Aug 26, 2025; 17(8): 109657 Published online Aug 26, 2025. doi: 10.4330/wjc.v17.i8.109657
Lepodisiran: From genetic targeting to cardiovascular promise: A detailed narrative review of the literature
Affan Faisal, Abdul Basit, Abdullah Iftikhar, Muneeb Saifullah, M Khalil ur Rehmaan, Abdul M Basil
Affan Faisal, Abdul Basit, Abdullah Iftikhar, Muneeb Saifullah, Department of Medicine, King Edward Medical University, Lahore 54000, Punjab, Pakistan
M Khalil ur Rehmaan, Department of Medicine, Sialkot Medical College, Sialkot 51040, Punjab, Pakistan
Abdul M Basil, Department of Medicine, Spinghar Medical University, Kabul 1001, Afghanistan
Author contributions: Faisal A and Basit A gave study conception; Basit A, Faisal A, Iftikhar A, Saifullah M and Rehman MKU wrote the manuscript; Basil AM supervised the study; All the authors proofread the manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Abdul M Basil, MD, Doctor, Department of Medicine, Spinghar Medical University, 4th Alley, Char Rahe Qambar Kabul, Kabul 1001, Afghanistan. abdulmaboodbasil@outlook.com
Received: May 19, 2025 Revised: June 14, 2025 Accepted: August 4, 2025 Published online: August 26, 2025 Processing time: 96 Days and 8 Hours
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.
Core Tip: Lepodisiran is a novel N-acetylgalactosamine-conjugated small interfering RNA that durably reduces lipoprotein(a) [Lp(a)] levels by silencing hepatic LPA message RNA expression. It offers up to 94% sustained Lp(a) reduction with minimal side effects and extended dosing intervals (6-12 months). This therapeutic breakthrough addresses a key residual cardiovascular risk factor previously untreatable with conventional lipid-lowering agents.
