APOC3 siRNA and ASO therapy for dyslipidemia
Abstract
Purpose of review The aim of this review is to present the clinical indications of apolipoprotein C-III (apoC3) inhibition in the therapeutic arsenal for the treatment of lipid disorders and associated risks and to compare the most advanced modalities of apoC3 inhibition currently available or in development, specifically APOC3 antisense oligonucleotides (ASO) and small interfering RNA (siRNA). Recent findings ApoC3 inhibition significantly decreases triglyceride levels by mechanisms coupling both lipoprotein lipase (LPL) upregulation and LPL-independent mechanisms. The main apoC3 inhibitors in advanced clinical development are the GalNAc-ASO olezarsen and the GalNAc-siRNA plozasiran. Clinical studies conducted with volanesorsen, the olezarsen precursor, showed a favorable effect on hepatic steatosis (nonalcoholic fatty liver disease, NAFLD). Olezarsen does not appear to be associated with the main side effects attributed to volanesorsen including thrombocytopenia. Plozasiran is in advanced clinical development and requires subcutaneous injection every 3 months and present to-date an efficacy and safety profile comparable to that of the monthly ASO. Summary Inhibition of apoC3 is effective across all the spectrum of hypertriglyceridemia, might have a favorable effect on hepatic steatosis (NAFLD) and the effect of apoC3 inhibition on cardiovascular risk is not limited to its effect on plasma triglycerides. APOC3 GalNAc-conjugated ASO and siRNA are both effective in decreasing…
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Both Olezarsen and Plozasiran have demonstrated efficacy in reducing plasma apoC-III and triglyceride levels.
“Both have demonstrated efficacy in reducing plasma apoC-III and triglyceride levels [22].”
From Efficacy and safety of Olezarsen in treating hypertriglyceridemia: a systematic review and meta-analysis of randomized controlled trials (2025) · cites this paper as [22]
The primary apo C-III inhibitors in advanced clinical development are GalNAc-ASO Olezarsen and ARO-APOC3 Plozasiran.
“The primary apo C-III inhibitors in advanced clinical development are GalNAc-ASO Olezarsen and ARO-APOC3 Plozasiran.”
From Efficacy and safety of Olezarsen in treating hypertriglyceridemia: a systematic review and meta-analysis of randomized controlled trials (2025) · cites this paper as [22]
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“Both have demonstrated efficacy in reducing plasma apoC-III and triglyceride levels [22].”
- Authors
- Chebli, J., Larouche, M., & Gaudet, D.
- Affiliations
- Université de Montréal (CA)
- Corresponding author
- Gaudet, Daniel
- Venue
- Current Opinion in Endocrinology, Diabetes & Obesity
- Published
- 2024-02-09
- Volume
- 31
- Issue
- 2
- Pages
- 70-77
- ISSN
- 1752-296X (ISSN-L)
- 1752-2978
- OpenAlex
- W4391707159
- Cited by
- 35
- References
- 9
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 9
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Endocrinology Diabetes and Obesity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- apolipoprotein C-III, hypertriglyceridemia, dyslipidemia, antisense oligonucleotides, siRNA, olezarsen, plozasiran, volanesorsen, lipoprotein lipase, triglyceride lowering, non-alcoholic fatty liver disease, hepatic steatosis, thrombocytopenia, cardiovascular risk
- MeSH terms
- Humans, Triglycerides, Oligonucleotides, Antisense, RNA, Small Interfering, Dyslipidemias, Apolipoprotein C-III, Non-alcoholic Fatty Liver Disease
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