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Cited by 215Lipid metabolism and disordersLipoproteins and Cardiovascular HealthRNA Interference and Gene Delivery

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia

Ballantyne, Christie M., Vasas, Szilard, Azizad, Masoud, Clifton, Peter, Rosenson, Robert S., Chang, Ting, Melquist, Stacey, Zhou, Rong, Mushin, Ma’an, Leeper, Nicholas J., Hellawell, Jennifer, Gaudet, Daniel·2024·New England Journal of Medicine
DOI 10.1056/nejmoa2404143
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Abstract

BACKGROUND: Persons with mixed hyperlipidemia are at risk for atherosclerotic cardiovascular disease due to an elevated non-high-density lipoprotein (HDL) cholesterol level, which is driven by remnant cholesterol in triglyceride-rich lipoproteins. The metabolism and clearance of triglyceride-rich lipoproteins are down-regulated through apolipoprotein C3 (APOC3)-mediated inhibition of lipoprotein lipase. METHODS: We carried out a 48-week, phase 2b, double-blind, randomized, placebo-controlled trial evaluating the safety and efficacy of plozasiran, a hepatocyte-targeted APOC3 small interfering RNA, in patients with mixed hyperlipidemia (i.e., a triglyceride level of 150 to 499 mg per deciliter and either a low-density lipoprotein [LDL] cholesterol level of ≥70 mg per deciliter or a non-HDL cholesterol level of ≥100 mg per deciliter). The participants were assigned in a 3:1 ratio to receive plozasiran or placebo within each of four cohorts. In the first three cohorts, the participants received a subcutaneous injection of plozasiran (10 mg, 25 mg, or 50 mg) or placebo on day 1 and at week 12 (quarterly doses). In the fourth cohort, participants received 50 mg of plozasiran or placebo on day 1 and at week 24 (half-yearly dose). The data from the participants who received placebo were pooled. The primary end point was the percent change in fasting triglyceride level at week 24. RESULTS: A total of 353 participants underwent randomization. At week 24, significant reductions in the fasting triglyceride level were observed with plozasiran, with differences, as compared with placebo, in the least-squares mean percent change from baseline of -49.8 percentage points (95% confidence interval [CI], -59.0 to -40.6) with the 10-mg-quarterly dose, -56.0 percentage points (95% CI, -65.1 to -46.8) with the 25-mg-quarterly dose, -62.4 percentage points (95% CI, -71.5 to -53.2) with the 50-mg-quarterly dose, and -44.2 percentage points (95% CI, -53.4 to -35.0) with the 50-mg-half-yearly dose (P<0.001 for all comparisons). Worsening glycemic control was observed in 10% of the participants receiving placebo, 12% of those receiving the 10-mg-quarterly dose, 7% of those receiving the 25-mg-quarterly dose, 20% of those receiving the 50-mg-quarterly dose, and 21% of those receiving the 50-mg-half-yearly dose. CONCLUSIONS: In this randomized, controlled trial involving participants with mixed hyperlipidemia, plozasiran, as compared with placebo, significantly reduced triglyceride levels at 24 weeks. A clinical outcomes trial is warranted. (Funded by Arrowhead Pharmaceuticals; MUIR ClinicalTrials.gov number NCT04998201.).

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Crossref · 10.1056/nejmoa2404143

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  1. Jacobsen A Duffy E Blumenthal RS Martin SS. Clinical review on triglycerides. Washington DC: American College of Cardiology March 4 2020 (https://www.acc.org/Latest-in-Cardiology/Articles/2020/03/03/15/08/Clinical-Review-on-Triglycerides).

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Metadata

Authors
Ballantyne, C. M., Vasas, S., Azizad, M., Clifton, P., Rosenson, R. S., Chang, T., Melquist, S., Zhou, R., Mushin, M., Leeper, N. J., Hellawell, J., & Gaudet, D.
Affiliations
  • Royal Adelaide Hospital (AU)
  • From the Baylor College of Medicine and the Texas Heart Institute, Houston (C.M.B.); Borbánya Praxis, Nyíregyháza, Hungary (S.V.); Valley Clinical Trials, Northridge (M.A.), Arrowhead Pharmaceuticals, Pasadena (T.C., S.M., R.Z., M.M., J.H.), and the Stanford School of Medicine, Stanford (N.J.L.) — all in California; the Royal Adelaide Hospital, Adelaide, SA, Australia (P.C.); the Icahn School of Medicine at Mount Sinai, New York (R.S.R.); and the Department of Medicine, Université de Montréal and Ecogene-21, Quebec, QC, Canada (D.G.).
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2024-09-12
Volume
391
Issue
10
Pages
899-912
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa2404143
OpenAlex
W4399087766
Semantic Scholar
c67a77a19492dfb8d4608c1ccc2c06e5e7c68abe
Cited by
210
References
44
Citations by year
2026: 73 · 2025: 106 · 2024: 30
FWCI
55.75
Type
journal article
Language
en
Open access
closed
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
Arrowhead Pharmaceuticals
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
plozasiran, apolipoprotein C-III, siRNA, mixed dyslipidemia, triglyceride-rich lipoproteins, remnant cholesterol, non-HDL cholesterol, lipoprotein lipase inhibition, triglyceride lowering, atherosclerotic cardiovascular disease, dose comparison, safety and tolerability, subcutaneous injection
MeSH terms
RNAi Therapeutics, Adult, Aged, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Hyperlipidemias, Cholesterol, LDL, Male, Middle Aged, Triglycerides, RNA, Small Interfering, Apolipoprotein C-III

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