Use of Plozasiran Across a Spectrum of Hypertriglyceridemia: Long-Term Efficacy and Safety Data From the Open-Label Extension Period of Shasta-2 and Muir Trials

Authors

• Christie M Ballantyne
• Alexis Baass
• Robert S Rosenson
• Robert A Hegele
• Stephen J Nicholls
• Szilard Vasas
• Peter Clifton
• Kathryn J Lucas
• Denes Pall
• Rong Zhou
• Nicholas J Leeper
• Jennifer Hellawell
• Lalitha Aiyer
• Gerald F Watts
• Daniel Gaudet

Language

English

Publication Date

6-1-2026

Journal

American Journal of Preventive Cardiology

DOI

10.1016/j.ajpc.2026.101523

PMID

42291067

PMCID

PMC13261268

PubMedCentral® Posted Date

3-24-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Plozasiran, a hepatocyte-targeted siRNA against apolipoprotein C-III, has demonstrated substantial reductions in triglycerides (TGs) and related atherogenic lipoproteins across a spectrum of hypertriglyceridemia (HTG), leading to its approval for familial chylomicronemia syndrome in the United States, and subsequently in Canada and China. Long-term data suggest maintenance of these effects beyond the blinded treatment periods, supporting further evaluation of plozasiran across a broad spectrum of HTG.

Methods: Safety and efficacy were assessed in this open-label extension (OLE) of two phase 2b, randomized, double-blind trials, SHASTA-2 (n = 229) including patients with severe HTG (TG >500 mg/dL) and MUIR (n = 353) including patients with mixed hyperlipidemia (TG 150-499 mg/dL, LDL-C ≥ 70 mg/dL or non-HDL-C ≥ 100 mg/dL). Participants initially received plozasiran at the assigned dose level in the randomized study before eventually transitioning to a regimen of 25 mg Q3M. Treatment-emergent adverse events (TEAEs), change in fasting TGs, and atherogenic lipoproteins were measured over a two-year follow-up.

Results: Plozasiran produced sustained TG reductions relative to baseline, over 24 months in the OLE. In SHASTA-2, mean TG reductions from baseline were -77% and -79% at Months 12 and 24, respectively, compared with -71%, at Month 6 of the index study (25 mg). In MUIR, reductions were -62% and -63%, versus -56% at Month 6, compared to baseline. Favorable effects were also observed for other secondary endpoints including remnant cholesterol, non-HDL-C, ApoB, HDL-C, and LDL-C. Common TEAEs included diabetes, COVID-19, upper respiratory tract infection, and back pain, consistent with prior studies; HbA1c levels remained stable.

Conclusions: Long-term open-label treatment with plozasiran resulted in sustained TG reductions compared to baseline, across a broad range of HTG, with a safety profile consistent with earlier trials. (Funded by Arrowhead Pharmaceuticals, Inc.; ClinicalTrials.gov number NCT05413135).

Keywords

ARO-APOC3, Familial chylomicronemia syndrome, Hypertriglyceridemia, Long-term, Mixed hyperlipidemia, Open-label, Plozasiran

Published Open-Access

yes

Recommended Citation

Ballantyne, Christie M; Baass, Alexis; Rosenson, Robert S; et al., "Use of Plozasiran Across a Spectrum of Hypertriglyceridemia: Long-Term Efficacy and Safety Data From the Open-Label Extension Period of Shasta-2 and Muir Trials" (2026). Faculty, Staff and Students Publications. 6703.
https://digitalcommons.library.tmc.edu/baylor_docs/6703