{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:28:06Z","timestamp":1787311686913,"version":"build-2736575974"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Am J Cardiovasc Drugs"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1007\/s40256-026-00808-6","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:42:23Z","timestamp":1782283343000},"page":"513-522","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Pharmacology of Plozasiran"],"prefix":"10.1007","volume":"26","author":[{"given":"Jessica","family":"Huston","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dontia","family":"Orey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelli","family":"Corona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Ashchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Ashchi","family":"Lachapelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Deeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Deeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rambod","family":"Rouhbakhsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Berner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sutton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasim","family":"Deeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majdi","family":"Ashchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Azarbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6401-4888","authenticated-orcid":false,"given":"Rebecca F.","family":"Goldfaden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"issue":"4","key":"808_CR1","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/joim.13016","volume":"287","author":"A Baass","year":"2020","unstructured":"Baass A, Paquette M, Bernard S, Hegele RA. Familial chylomicronemia syndrome: an under-recognized cause of severe hypertriglyceridaemia. J Intern Med. 2020;287(4):340\u20138. https:\/\/doi.org\/10.1111\/joim.13016.","journal-title":"J Intern Med"},{"issue":"10","key":"808_CR2","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1016\/j.jacc.2018.06.042","volume":"72","author":"NP Shah","year":"2018","unstructured":"Shah NP, Cho L, Ahmed HM. Familial chylomicronemia syndrome. J Am Coll Cardiol. 2018;72(10):1177\u20139. https:\/\/doi.org\/10.1016\/j.jacc.2018.06.042.","journal-title":"J Am Coll Cardiol"},{"key":"808_CR3","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-5451391\/v1","author":"MC Izquierdo","year":"2024","unstructured":"Izquierdo MC, Cabodevilla AG, Basu D, et al. Hyperchylomicronemia causes endothelial cell inflammation and increases atherosclerosis. Preprint Res Sq. 2024. https:\/\/doi.org\/10.21203\/rs.3.rs-5451391\/v1. (Published 2024 Nov 25).","journal-title":"Preprint. Res Sq."},{"issue":"1","key":"808_CR4","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1056\/NEJMoa1307095","volume":"371","author":"J Crosby","year":"2014","unstructured":"TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute, Crosby J, Peloso GM, et al. Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med. 2014;371(1):22\u201331. https:\/\/doi.org\/10.1056\/NEJMoa1307095.","journal-title":"N Engl J Med"},{"issue":"10","key":"808_CR5","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1056\/NEJMoa2404143","volume":"391","author":"CM Ballantyne","year":"2024","unstructured":"Ballantyne CM, Vasas S, Azizad M, et al. Plozasiran, an RNA interference agent targeting APOC3, for mixed hyperlipidemia. N Engl J Med. 2024;391(10):899\u2013912. https:\/\/doi.org\/10.1056\/NEJMoa2404143.","journal-title":"N Engl J Med"},{"issue":"7","key":"808_CR6","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1001\/jamacardio.2024.0959","volume":"9","author":"D Gaudet","year":"2024","unstructured":"Gaudet D, Pall D, Watts GF, et al. Plozasiran (ARO-APOC3) for severe hypertriglyceridemia: the SHASTA-2 randomized clinical trial. JAMA Cardiol. 2024;9(7):620\u201330. https:\/\/doi.org\/10.1001\/jamacardio.2024.0959.","journal-title":"JAMA Cardiol"},{"key":"808_CR7","unstructured":"Study of Plozasiran in Adults with Severe Hypertriglyceridemia (SHASTA-4). ClinicalTrials.gov identifier: NCT06347016. Available from: https:\/\/clinicaltrials.gov\/study\/NCT06347016. Accessed 2026 Jan 09."},{"issue":"1","key":"808_CR8","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-025-01345-4","volume":"27","author":"S Tsimikas","year":"2025","unstructured":"Tsimikas S. Anti-apoC-III therapies and implications for treatment of pancreatitis and cardiovascular disease. Curr Atheroscler Rep. 2025;27(1):103. https:\/\/doi.org\/10.1007\/s11883-025-01345-4.","journal-title":"Curr Atheroscler Rep"},{"key":"808_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00474","volume":"11","author":"J Bor\u00e9n","year":"2020","unstructured":"Bor\u00e9n J, Packard CJ, Taskinen MR. The roles of ApoC-III on the metabolism of triglyceride-rich lipoproteins in humans. Front Endocrinol (Lausanne). 2020;11:474. https:\/\/doi.org\/10.3389\/fendo.2020.00474.","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"8","key":"808_CR10","doi-asserted-by":"publisher","first-page":"2855","DOI":"10.1172\/JCI86610","volume":"126","author":"PL Gordts","year":"2016","unstructured":"Gordts PL, Nock R, Son NH, et al. ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors. J Clin Invest. 2016;126(8):2855\u201366. https:\/\/doi.org\/10.1172\/JCI86610.","journal-title":"J Clin Invest"},{"issue":"23","key":"808_CR11","doi-asserted-by":"publisher","first-page":"2200","DOI":"10.1056\/NEJMoa1400284","volume":"371","author":"D Gaudet","year":"2014","unstructured":"Gaudet D, Brisson D, Tremblay K, et al. Targeting APOC3 in the familial chylomicronemia syndrome. N Engl J Med. 2014;371(23):2200\u20136. https:\/\/doi.org\/10.1056\/NEJMoa1400284.","journal-title":"N Engl J Med"},{"key":"808_CR12","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2024.2414126","author":"XL Tang","year":"2024","unstructured":"Tang XL, Hooper AJ, Burnett JR. Assessing the clinical potential of plozasiran, an APOC3 siRNA therapy for severe hypertriglyceridemia. Expert Opin Investig Drugs. 2024. https:\/\/doi.org\/10.1080\/13543784.2024.2414126.","journal-title":"Expert Opin Investig Drugs"},{"issue":"1","key":"808_CR13","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1186\/s12933-025-02929-9","volume":"24","author":"F Wang","year":"2025","unstructured":"Wang F, You D, Niu X, Shi J, Li Y, Qi L, et al. Safety, pharmacokinetics and pharmacodynamics of Plozasiran in Chinese healthy volunteers. Cardiovasc Diabetol. 2025;24(1):399. https:\/\/doi.org\/10.1186\/s12933-025-02929-9.","journal-title":"Cardiovasc Diabetol"},{"key":"808_CR14","unstructured":"Study of ARO-APOC3 in Healthy Volunteers, Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome (FCS). ClinicalTrials.gov identifier: NCT03783377. Available from: https:\/\/clinicaltrials.gov\/study\/NCT03783377. Accessed 2026 April 21."},{"issue":"12","key":"808_CR15","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200325","volume":"2","author":"D Gaudet","year":"2023","unstructured":"Gaudet D, Clifton P, Sullivan D, et al. RNA interference therapy targeting apolipoprotein C-III in hypertriglyceridemia. NEJM Evidence. 2023;2(12):EVIDoa2200325. https:\/\/doi.org\/10.1056\/EVIDoa2200325.","journal-title":"NEJM Evidence"},{"issue":"1","key":"808_CR16","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1161\/ATVBAHA.118.311476","volume":"39","author":"G Reyes-Soffer","year":"2019","unstructured":"Reyes-Soffer G, Sztalryd C, Horenstein RB, et al. Effects of APOC3 heterozygous deficiency on plasma lipid and lipoprotein metabolism. Arterioscler Thromb Vasc Biol. 2019;39(1):63\u201372. https:\/\/doi.org\/10.1161\/ATVBAHA.118.311476.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"8","key":"808_CR17","doi-asserted-by":"publisher","DOI":"10.1210\/jcemcr\/luaf146","volume":"3","author":"M Larouche","year":"2025","unstructured":"Larouche M, Ballantyne C, Dufour J, Brisson D, Given B, Gaudet D. Glycerol kinase gene variant as a cause of pseudohypertriglyceridemia and apparent poor response to plozasiran. JCEM Case Reports. 2025;3(8):luaf146. https:\/\/doi.org\/10.1210\/jcemcr\/luaf146.","journal-title":"JCEM Case Reports"},{"issue":"2","key":"808_CR18","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1056\/NEJMoa2409368","volume":"392","author":"GF Watts","year":"2025","unstructured":"Watts GF, Rosenson RS, Hegele RA, et al. Plozasiran for managing persistent chylomicronemia and pancreatitis risk. N Engl J Med. 2025;392(2):127\u201337. https:\/\/doi.org\/10.1056\/NEJMoa2409368.","journal-title":"N Engl J Med"},{"issue":"3","key":"808_CR19","doi-asserted-by":"publisher","first-page":"e106","DOI":"10.1016\/j.jacl.2025.04.153","volume":"19","author":"P Moriarty","year":"2025","unstructured":"Moriarty P, Ballantyne C, Romeo S, et al. SHASTA-5 rationale and design: randomized, double-blind, placebo-controlled study to evaluate plozasiran efficacy and safety in sHTG at risk for AP. J Clin Lipidol. 2025;19(3):e106\u20137. https:\/\/doi.org\/10.1016\/j.jacl.2025.04.153.","journal-title":"J Clin Lipidol"},{"key":"808_CR20","unstructured":"Study of Plozasiran in Adults With Severe Hypertriglyceridemia at Risk of Acute Pancreatitis (SHASTA-5). ClinicalTrials.gov identifier: NCT06880770. Available from: https:\/\/clinicaltrials.gov\/study\/NCT06880770?tab=researcher. Accessed 2026 Apr 21."},{"key":"808_CR21","unstructured":"Phase 3 Study of Plozasiran in Adults With Hypertriglyceridemia (MUIR-3). ClinicalTrials.gov identifier: NCT06347133. Available from: https:\/\/clinicaltrials.gov\/study\/NCT06347133?tab=researcher. Accessed 2026 Apr 21."},{"key":"808_CR22","unstructured":"Long-Term Safety and Efficacy of Plozasiran in Adults With Hypertriglyceridemia (SHASTA-10). ClinicalTrials.gov identifier: NCT06822790. Available from: https:\/\/clinicaltrials.gov\/study\/NCT06822790. Accessed 2026 Apr 21."},{"key":"808_CR23","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-025-07798-8","author":"P Sydhom","year":"2025","unstructured":"Sydhom P, Al-Quraishi B, Gohar A, et al. The efficacy and safety of plozasiran on lipid profile in dyslipidemic disorders: a systematic review and meta-analysis. Cardiovasc Drugs Ther. 2025. https:\/\/doi.org\/10.1007\/s10557-025-07798-8.","journal-title":"Cardiovasc Drugs Ther"},{"issue":"1","key":"808_CR24","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.70052","volume":"67","author":"M Larouche","year":"2026","unstructured":"Larouche M, Brisson D, Roy N, et al. Course of pregnancy in a woman with familial chylomicronemia syndrome treated with plozasiran, a small interfering RNA against ApoC3. JIMD Rep. 2026;67(1):e70052. https:\/\/doi.org\/10.1002\/jmd2.70052.","journal-title":"JIMD Rep"},{"key":"808_CR25","unstructured":"Feingold KR. Pancreatitis Secondary to Hypertriglyceridemia. Endotext. September 24, 2025. Accessed Dec 21, 2025."},{"issue":"11","key":"808_CR26","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1016\/j.eprac.2024.08.013","volume":"30","author":"ABM Kamrul-Hasan","year":"2024","unstructured":"Kamrul-Hasan ABM, Dutta D, Nagendra L, Mondal S, Bhattacharya S, Kalra S. Safety and efficacy of the novel RNA interference therapies for hypertriglyceridemia and mixed hyperlipidemia management: a systematic review and meta-analysis. Endocr Pract. 2024;30(11):1103\u201312.","journal-title":"Endocr Pract"},{"issue":"6","key":"808_CR27","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1007\/s40292-024-00677-7","volume":"31","author":"G Olatunji","year":"2024","unstructured":"Olatunji G, Ogieuhi IJ, Kokori E, et al. Olezarsen and plozasiran in dyslipidemia management: a narrative review of clinical trials. High Blood Press Cardiovasc Prev. 2024;31(6):567\u201376. https:\/\/doi.org\/10.1007\/s40292-024-00677-7.","journal-title":"High Blood Press Cardiovasc Prev"},{"issue":"2","key":"808_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.59657\/2996-3095.brs.24.016","volume":"2","author":"N Mikhail","year":"2024","unstructured":"Mikhail N, Wali S. New approaches for treatment of hypertriglyceridemia. J Endocrinol Diabetes Res. 2024;2(2):1\u20136. https:\/\/doi.org\/10.59657\/2996-3095.brs.24.016.","journal-title":"J Endocrinol Diabetes Res."},{"issue":"1","key":"808_CR29","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s11883-025-01295-x.PMID:40257687;PMCID:PMC12011915","volume":"27","author":"MC Izar","year":"2025","unstructured":"Izar MC, Fonseca FAH. Novel therapeutics for familial chylomicronemia syndrome. Curr Atheroscler Rep. 2025;27(1):51. https:\/\/doi.org\/10.1007\/s11883-025-01295-x.PMID:40257687;PMCID:PMC12011915.","journal-title":"Curr Atheroscler Rep"},{"key":"808_CR30","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1056\/NEJMoa1715944","volume":"381","author":"JL Witztum","year":"2019","unstructured":"Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, et al. Volanesorsen and triglyceride levels in familial chylomicronemia syndrome. N Engl J Med. 2019;381:531\u201342. https:\/\/doi.org\/10.1056\/NEJMoa1715944.","journal-title":"N Engl J Med"},{"key":"808_CR31","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/joim.13059","volume":"288","author":"A Langsted","year":"2020","unstructured":"Langsted A, Madsen CM, Nordestgaard BG. Contribution of remnant cholesterol to cardiovascular risk. J Intern Med. 2020;288:116\u201327.","journal-title":"J Intern Med"}],"container-title":["American Journal of Cardiovascular Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40256-026-00808-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40256-026-00808-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40256-026-00808-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T10:45:45Z","timestamp":1787309145000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40256-026-00808-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":31,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["808"],"URL":"https:\/\/doi.org\/10.1007\/s40256-026-00808-6","relation":{},"ISSN":["1175-3277","1179-187X"],"issn-type":[{"value":"1175-3277","type":"print"},{"value":"1179-187X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]},"assertion":[{"value":"28 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"No external funding was used in the preparation of this article.","order":1,"name":"Ethics","label":"Funding","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Jessica Huston, Dontia Orey, Kelli Corona, Andrea Ashchi Lachapelle, Andrew Ashchi, Jason Berner, Alexander Deeb, Elias Deeb, David Sutton, Wasim Deeb, Majdi Ashchi, Amir Azarbal, Rambod Rouhbakhsh, and Rebecca F. Goldfaden declare that they have no potential conflicts of interest that might be relevant to the contents of this article.","order":2,"name":"Ethics","label":"Conflict of Interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Ethics Approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":4,"name":"Ethics","label":"Consent to Participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":5,"name":"Ethics","label":"Consent for Publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":6,"name":"Ethics","label":"Code Availability","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Data sharing is not applicable to this article as no datasets were generated.","order":7,"name":"Ethics","label":"Data Availability Statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Jessica Huston was involved in supervision, data curation, analysis, reviewing, editing, and writing. Dontia Orey was involved in data curation, analysis, and writing. Kelli Corona was involved in data curation, analysis, and writing. Andrea Ashchi Lachapelle was involved in data curation, writing, and analysis. Andrew Aschi was involved in data curation, analysis, and writing. Elias Deeb was involved in data curation, analysis, and writing. Alexander Deeb was involved in data curation, analysis, and writing. Jason Berner was involved in reviewing and editing. Rambod Rouhbakhsh was involved in reviewing and editing. David Sutton was involved in reviewing and editing. Wasim Deeb was involved in reviewing and editing. Majdi Ashchi was involved in reviewing and editing. Amir Azarbal was involved in reviewing and editing. Rebecca Goldfaden was involved in the conceptualization, project administration, reviewing and editing.","order":8,"name":"Ethics","label":"Authors' Contributions","group":{"name":"EthicsHeading","label":"Declarations"}}]}}