Assessing the clinical potential of plozasiran, an APOC3 siRNA therapy for severe hypertriglyceridemia
Abstract
1. Mild-to-moderate hypertriglyceridemia (HTG), defined as a fasting plasma triglyceride (TG) of 150-499 mg/dL (1.7-5.6 mmol/L), is a common clinical finding on biochemical laboratory testing. Epid...
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Compared with earlier antisense oligonucleotide approaches, siRNAs are associated with less frequent dosing.
“Compared with earlier antisense oligonucleotide approaches, siRNAs are associated with less frequent dosing and improved platelet safety (Tang et al., 2024).”
From Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis (2026) · cites this paper as Tang et al., 2024
Compared with earlier antisense oligonucleotide approaches, siRNAs are associated with improved platelet safety.
“Compared with earlier antisense oligonucleotide approaches, siRNAs are associated with less frequent dosing and improved platelet safety (Tang et al., 2024).”
From Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis (2026) · cites this paper as Tang et al., 2024
Cites
Loss-of-Function Mutations in <i>APOC3,</i> Triglycerides, and Coronary Disease
The TG and HDL Working Group of the Exome Sequencing Project, N. H. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1307095 · Cited by 1,071 · see citing works
Loss-of-Function Mutations in <i>APOC3</i> and Risk of Ischemic Vascular Disease
Jørgensen, A. B., Frikke-Schmidt, R., Nordestgaard, B. G., & Tybjærg-Hansen, A. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1308027 · Cited by 919 · see citing works
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Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia
Rosenson, R. S., Gaudet, D., Hegele, R. A., Ballantyne, C. M., Nicholls, S. J., Lucas, K. J., San Martin, J., Zhou, R., Muhsin, M., Chang, T., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2404147 · Cited by 213 · see citing works
Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia
Ballantyne, C. M., Vasas, S., Azizad, M., Clifton, P., Rosenson, R. S., Chang, T., Melquist, S., Zhou, R., Mushin, M., Leeper, N. J., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2404143 · Cited by 210 · see citing works
Tardif, J.-C., Karwatowska-Prokopczuk, E., Amour, E. S., Ballantyne, C. M., Shapiro, M. D., Moriarty, P. M., Baum, S. J., Hurh, E., Bartlett, V. J., Kingsbury, J., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehab820 · Cited by 210 · see citing works
The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans
Borén, J., Packard, C. J., & Taskinen, M.-R. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00474 · Cited by 196 · see citing works
Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia
Gaudet, D., Pall, D., Watts, G. F., Nicholls, S. J., Rosenson, R. S., Modesto, K., San Martin, J., Hellawell, J., & Ballantyne, C. M. (2024) · JAMA Cardiology · doi:10.1001/jamacardio.2024.0959 · Cited by 172 · cited 1× · see citing works
“SHASTA-2 (NCT04720534) was a placebo-controlled, double-blind, dose-ranging, phase IIb randomized clinical trial investigating the tolerability, efficacy, and safety of plozasiran in adults with severe HTG on stable lipid-lowering treatment [14].”
Rosenson, R. S., Gaudet, D., Ballantyne, C. M., Baum, S. J., Bergeron, J., Kershaw, E. E., Moriarty, P. M., Rubba, P., Whitcomb, D. C., Banerjee, P., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02222-w · Cited by 140 · see citing works
A Comprehensive Update on the Chylomicronemia Syndrome
Goldberg, R. B., & Chait, A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.593931 · Cited by 121 · see citing works
Volanesorsen to Prevent Acute Pancreatitis in Hypertriglyceridemia
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RNA Interference Therapy Targeting Apolipoprotein C-III in Hypertriglyceridemia
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Gao, Y., Bai, Y., Mu, X., & Pang, X. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1736821 · Cited by 4 · see citing works
“Compared with earlier antisense oligonucleotide approaches, siRNAs are associated with less frequent dosing and improved platelet safety (Tang et al., 2024).”
The Crosstalk Between Non-Coding RNAs and Lipid Metabolism in Chronic Disease Progression
Zayani, Z., Matinahmadi, A., Tavakolpournegari, A., Moosavi, S. S., & Bidooki, S. H. (2025) · Lipidology · doi:10.3390/lipidology2040019
Clinical identification of familial chylomicronemia syndrome and novel therapeutic options
Hang, S., & Hegele, R. A. (2026) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2026.2661212
Clinical Pharmacology of Plozasiran
Huston, J., Orey, D., Corona, K., Ashchi, A., Ashchi, A., Deeb, E., Deeb, A., Rouhbakhsh, R., Berner, J., Sutton, D., et al. (2026) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-026-00808-6
- Authors
- Tang, X. L., Hooper, A. J., & Burnett, J. R.
- Affiliations
- Royal Perth Hospital (AU)
- The University of Western Australia (AU)
- Corresponding author
- Burnett, John R.
- Venue
- Expert Opinion on Investigational Drugs
- Publisher
- Informa UK Limited
- Published
- 2024-10-09
- Volume
- 33
- Issue
- 11
- Pages
- 1099-1102
- ISSN
- 1354-3784 (ISSN-L)
- 1744-7658
- OpenAlex
- W4403156997
- Cited by
- 4
- References
- 15
- Citations by year
- 2026: 3 · 2025: 1
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Investigational Drugs (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- 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
- plozasiran, apolipoprotein C-III, siRNA therapeutics, severe hypertriglyceridemia, triglyceride-lowering therapy
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