{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:13:45Z","timestamp":1792592025090,"version":"4.5.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Lipids Health Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Olezarsen is a GalNAc<jats:sub>3<\/jats:sub>-conjugated, hepatic-targeted antisense oligonucleotide that lowers apolipoprotein C-III (apoC-III) and triglyceride levels. The efficacy and safety of olezarsen has not previously been studied in ethnically diverse American populations. The aim of this study is to assess the effect of olezarsen in healthy Japanese Americans.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A randomized, placebo-controlled, double-blind phase 1 study was performed in 28 healthy Japanese American participants treated with olezarsen in single-ascending doses (SAD; 30, 60, 90 mg) or multiple doses (MD; 60 mg every 4 weeks for 4 doses). The primary, secondary, and exploratory objectives were safety and tolerability, pharmacokinetics, and effects of olezarsen on fasting serum triglycerides and apoC-III, respectively.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>There were 20 participants (16 active:4 placebo) in the SAD part of the study, and 8 participants (6 active:2 placebo) in the MD part of the study. For the primary endpoint, no serious adverse events or clinically relevant laboratory abnormalities were reported. The majority of olezarsen plasma exposure occurred within 24 h post-dose. In the SAD cohorts at Day 15 the percentage reduction in apoC-III\/TG was\u2009\u2212\u200939.4%\/\u2009\u2212\u200917.8%,\u2009\u2212\u200960.8%\/\u2009\u2212\u200952.7%, and\u2009\u2212\u200968.1%\/\u2009\u2212\u200939.2% in the 30, 60 and 90 mg doses, respectively, vs 2.3%\/44.5% increases in placebo. In the MD cohort, at Day 92 the percentage reduction in apoC-III\/TG was\u2009\u2212\u200981.6\/\u2009\u2212\u200973.8% vs\u2009\u2212\u200917.2\/\u2009\u2212\u200940.8% reduction in placebo. Favorable changes were also present in VLDL-C, apoB and HDL-C.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Single- and multiple-dose administration of olezarsen was safe, was well tolerated, and significantly reduced apoC-III and triglyceride levels in healthy Japanese Americans.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12944-024-02297-5","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T04:01:47Z","timestamp":1727928107000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Efficacy and safety of olezarsen in lowering apolipoprotein C-III and triglycerides in healthy Japanese Americans"],"prefix":"10.1186","volume":"23","author":[{"given":"Ewa","family":"Karwatowska-Prokopczuk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Lesogor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-He","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Hoenlinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Margolskee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotirios","family":"Tsimikas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"key":"2297_CR1","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1097\/MOL.0b013e328352dc70","volume":"23","author":"Z Yao","year":"2012","unstructured":"Yao Z, Wang Y. 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All patients provided written informed consent before enrollment.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"N\/A.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare the following financial interests\/personal relationships which may be considered as potential competing interests. Ewa Karwatowska-Prokopczuk: Ionis Employee. Anastasia Lesogor: Novartis employee. Jing-He Yan: Novartis employee. Angelika Hoenlinger: Novartis employee. Alison Margolskee: Novartis employee. Lu Li: Ionis Employee. Sotirios Tsimikas: co-inventor and receives royalties from patents owned by University of California San Diego (UCSD) and is a co-founder and has an equity interest in Oxitope\u00a0and Kleanthi Diagnostics and has a dual appointment at UCSD and Ionis Pharmaceuticals. Although these relationships have been identified for conflict-of-interest management based on the overall scope of the project, the research findings included in this publication may not necessarily relate to the interests of the above companies. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"329"}}