Inclisiran as a siRNA Inhibitor of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9); Past, Present, and Future
Abstract
Reducing low-density lipoprotein cholesterol (LDL-C) levels has been shown to reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Statins are the foundation of LDL-C lowering therapy with other non-statin agents used in circumstances where goal LDL-C levels are not reached or owing to intolerance to adverse effects of statins. In 2003, the discovery of the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) system in promoting elevated LDL-C levels led to new avenues of drug development to achieve target LDL-C. In 2021, inclisiran, a small interfering ribonucleic acid (siRNA) molecule targeting PCSK9 was approved by the Food and Drug Administration (FDA). Inclisiran has demonstrated effective reductions of LDL-C, such as in the large phase-3 ORION-9, ORION-10, and ORION-11 trials in which it achieved LDL-C reductions of 39.7%, 52.3%, and 49.9%, respectively. This review discusses the current clinical evidence and ongoing clinical studies of inclisiran as well as analyzes other areas of PCSK9 inhibition development.
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The dual aspects of PCSK9 suppression and twice-yearly treatment schedule make inclisiran effective while creating better conditions for patients to adhere to their treatments.
“The dual aspects of PCSK9 suppression and twice-yearly treatment schedule make Inclisiran effective while creating better conditions for patients to adhere to their treatments [47, 72].”
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References 58 · Cited by 12
- Authors
- Mansoor, T., Rao, B. H., Gupta, K., Parikh, S. S., Abramov, D., Mehta, A., Al Rifai, M., Virani, S. S., Nambi, V., Minhas, A. M. K., & Koshy, S. K. G.
- Affiliations
- Western Michigan University (US)
- Henry Ford Hospital (US)
- Loma Linda University (US)
- Virginia Commonwealth University (US)
- Aga Khan University (PK)
- Baylor College of Medicine (US)
- Corresponding author
- Mansoor, Taha
- ORCID
- Venue
- American Journal of Cardiovascular Drugs
- Published
- 2024-12-20
- Volume
- 25
- Issue
- 3
- Pages
- 293-306
- ISSN
- 1175-3277 (ISSN-L)
- 1179-187X
- OpenAlex
- W4405632020
- Cited by
- 12
- References
- 58
- Citations by year
- 2026: 5 · 2025: 7
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- American Journal of Cardiovascular Drugs (publishedVersion)
- PubMed (publishedVersion)
- eCommons - AKU (Aga Khan University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- inclisiran, PCSK9 inhibition, siRNA, LDL cholesterol lowering, atherosclerotic cardiovascular disease, statin intolerance, PCSK9 inhibitors, lipid-lowering therapy
- MeSH terms
- Proprotein Convertase 9, PCSK9 Inhibitors, Animals, Anticholesteremic Agents, Humans, Cholesterol, LDL, RNA, Small Interfering
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