Inclisiran-will it fulfill its promise?
Seyed Saeed Tamehri Zadeh1, Federica Fogacci2, Farzad Hadaegh1
1Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Summary
Inclisiran, a novel siRNA therapy, effectively lowers low-density lipoprotein cholesterol (LDL-C) by inhibiting PCSK9 synthesis. This treatment shows promise as an adjunct therapy for atherosclerotic cardiovascular disease (ASCVD) prevention.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Genetics
Background:
- Elevated low-density lipoprotein cholesterol (LDL-C) is a primary risk factor for atherosclerotic cardiovascular disease (ASCVD).
- Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) offers an effective lipid-lowering strategy.
- Inclisiran is a small interfering RNA (siRNA) therapy targeting hepatic PCSK9 synthesis.
Purpose of the Study:
- To review the efficacy and safety of inclisiran.
- To assess inclisiran's role in primary and secondary ASCVD prevention.
- To evaluate inclisiran in familial hypercholesterolaemia (HeFH and HoFH).
Main Methods:
- Review of randomized clinical trials.
- Analysis of inclisiran's effect on LDL-C and PCSK9 levels.
- Evaluation of long-term safety and tolerability data.
Main Results:
- Inclisiran demonstrates robust and sustained LDL-C reduction across diverse patient groups.
- A twice-yearly dosing regimen may enhance treatment adherence.
- Long-term data (up to 6 years) show a favorable safety profile without dose adjustments for renal or hepatic impairment.
Conclusions:
- Inclisiran is a promising adjunct or alternative to existing lipid-lowering therapies.
- It is particularly beneficial for patients needing further LDL-C reduction.
- Ongoing outcome trials will further clarify its impact on ASCVD events.
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