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Updated: Jun 5, 2025
10:56
A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
Published on: September 15, 2018
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Inclisiran for the treatment of hypercholesterolaemia
Joel C Marrs1, Sarah L Anderson2
1College of Pharmacy, Department of Clinical Pharmacy & Translational Science, The University of Tennessee Health Science Center, Nashville, TN, USA.
Drugs in Context
|December 6, 2024
Summary
Inclisiran, a small interfering RNA (siRNA), effectively lowers LDL cholesterol by reducing PCSK9 production. This novel therapy offers a safe and consistent option for managing hyperlipidaemia.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- RNA Therapeutics
Background:
- Hyperlipidaemia, characterized by elevated LDL cholesterol, is a major risk factor for cardiovascular disease.
- Proprotein convertase subtilisin/kexin 9 (PCSK9) plays a crucial role in regulating LDL cholesterol levels.
- Current treatments often require lifelong adherence and may have limitations.
Purpose of the Study:
- To evaluate the efficacy and safety of inclisiran, a novel siRNA-based therapy, for lowering LDL cholesterol.
- To assess inclisiran's role as an adjunct to diet and statin therapy in adults with hyperlipidaemia.
Main Methods:
- Inclisiran utilizes small interfering RNA (siRNA) technology to silence PCSK9 mRNA translation in hepatocytes.
- This mechanism leads to reduced PCSK9 synthesis, decreased LDL receptor degradation, and enhanced LDL-C clearance.
- Clinical trials have assessed its efficacy and safety profile compared to placebo.
Main Results:
- Inclisiran demonstrated consistent LDL-C reduction ranging from 44-54%.
- The therapy was found to be safe, with no significant increase in serious adverse events compared to placebo.
- Approved by FDA (2021) and EMA (2020), inclisiran is indicated for primary hyperlipidaemia and heterozygous familial hypercholesterolaemia.
Conclusions:
- Inclisiran offers a potent and safe therapeutic option for lowering LDL cholesterol in patients with hyperlipidaemia.
- Its infrequent dosing regimen (initially, then every 6 months) may improve treatment adherence.
- Inclisiran is recognized as a valuable non-statin therapy option for high-risk cardiovascular patients.
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