{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:21:58Z","timestamp":1789741318148,"version":"4.0.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100014931","name":"Arrowhead Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014931","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Mixed hyperlipidaemia, characterized by elevated cholesterol and triglyceride (TG) levels, is associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). Angiopoietin-like protein 3 (ANGPTL3) regulates lipid metabolism through inhibition of lipoprotein and endothelial lipases. Loss-of-function variants in ANGPTL3 are associated with lower plasma TGs, cholesterol, and reduced ASCVD risk. Zodasiran, a hepatocyte-targeted small interfering RNA (siRNA) against ANGPTL3, demonstrated significant lipid lowering in the Phase 2b ARCHES-2 trial. This study aimed to evaluate the long-term safety and efficacy of zodasiran in adults with mixed hyperlipidaemia participating in the open-label extension (OLE) of ARCHES-2 (NCT04832971).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Adults with mixed hyperlipidaemia (fasting TGs: 1.7\u20135.6\u2005mmol\/L and LDL-C \u2265 1.8\u2005mmol\/L or non-HDL-C \u2265 2.59\u2005mmol\/L) who completed 9 months of randomized treatment with placebo or zodasiran [50, 100, or 200 mg subcutaneously every three months (Q3M)] were eligible for the OLE. The primary endpoint in the randomized double-blind study was percent change in median TGs from baseline to Month 6. Here, lipid parameters were assessed through 21 months of the OLE; with total follow-up of 24 months. Of 191 participants completing randomized treatment, 156 (82%) enrolled in the OLE. Over 24 months, zodasiran was generally well tolerated; five participants (3.2%) discontinued due to adverse events; one (0.6%) death, not considered treatment-related, occurred. Injection site reactions were mild. By Month 21, median TGs were reduced by \u221255% (95% confidence interval, \u221264, \u221243); remnant cholesterol by \u221257% [standard deviation (SD): 32]; LDL-C by \u22125% (SD: 40); and ApoB by \u221213% (SD: 21).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Zodasiran produced sustained reductions in TGs and atherogenic lipoproteins over 30 months and was well tolerated, supporting its potential as a long-term therapeutic option for mixed hyperlipidaemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwag376","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:39:22Z","timestamp":1784893162000},"source":"Crossref","is-referenced-by-count":1,"title":["Longer-term efficacy and safety of zodasiran in patients with mixed hyperlipidaemia"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5599-0633","authenticated-orcid":false,"given":"Robert S","family":"Rosenson","sequence":"first","affiliation":[{"name":"Lipids and Metabolism Program Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai , New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5185-3666","authenticated-orcid":false,"given":"Daniel","family":"Gaudet","sequence":"additional","affiliation":[{"name":"Department of Medicine, Universit\u00e9 de Montr\u00e9al, and ECOGENE 21, Montr\u00e9al, QC ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6432-1730","authenticated-orcid":false,"given":"Christie M","family":"Ballantyne","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine and the Texas Heart Institute , Houston, TX 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