Nicholas A Marston, Brian A Bergmark, Veronica J Alexander, Ewa Karwatowska-Prokopczuk, Yu Mi Kang, Filipe A Moura, Thomas A Prohaska, Andre Zimerman, Shuanglu Zhang, Sabina A Murphy, Sotirios Tsimikas, Robert P Giugliano, Marc S Sabatine
{"title":"Design and Rationale of the CORE -TIMI 72a and CORE2 -TIMI 72b Trials of Olezarsen in Patients with Severe Hypertriglyceridemia.","authors":"Nicholas A Marston, Brian A Bergmark, Veronica J Alexander, Ewa Karwatowska-Prokopczuk, Yu Mi Kang, Filipe A Moura, Thomas A Prohaska, Andre Zimerman, Shuanglu Zhang, Sabina A Murphy, Sotirios Tsimikas, Robert P Giugliano, Marc S Sabatine","doi":"10.1016/j.ahj.2025.03.003","DOIUrl":null,"url":null,"abstract":"<p><p>Severe hypertriglyceridemia (HTG), defined as a serum triglyceride (TG) concentration ≥500 mg/dl, is present in approximately 1 in every 500 individuals and carries direct clinical consequences, including pancreatitis, which can be life-threatening. Olezarsen is an investigational antisense oligonucleotide targeted to the mRNA for apolipoprotein C-III (apoC-III), a protein known to impair TG clearance by inhibiting lipoprotein lipase and the hepatic uptake of triglycerides and triglyceride-rich remnants. Olezarsen has been evaluated in patients with predominantly moderate HTG (150-499 mg/dl) and a rare genetic condition known as Familial Chylomicronemia Syndrome (FCS), with TG lowering effects of 53% and 44%, respectively, and reductions in pancreatitis among the FCS population. However, no dedicated trial has tested olezarsen in patients with severe HTG. In these two pivotal phase 3 trials, CORE -TIMI 72a (NCT05079919) and CORE2 -TIMI 72b (NCT05552326), over 1,000 patients with severe HTG will be randomized in a 2:1 fashion to either olezarsen (80 mg or 50 mg dose) or matching placebo. Patients will be treated for a total of 53 weeks and evaluated for the primary endpoint of percent change in TGs from baseline to 6 months compared to placebo. Pooled analyses of CORE and CORE2 will also assess olezarsen's effect on acute pancreatitis events and change in hepatic steatosis. Together, CORE -TIMI 72a (NCT05079919) and CORE2 -TIMI 72b (NCT05552326) are designed to establish the efficacy and safety of olezarsen in patients with severe HTG.</p>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American heart journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ahj.2025.03.003","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Severe hypertriglyceridemia (HTG), defined as a serum triglyceride (TG) concentration ≥500 mg/dl, is present in approximately 1 in every 500 individuals and carries direct clinical consequences, including pancreatitis, which can be life-threatening. Olezarsen is an investigational antisense oligonucleotide targeted to the mRNA for apolipoprotein C-III (apoC-III), a protein known to impair TG clearance by inhibiting lipoprotein lipase and the hepatic uptake of triglycerides and triglyceride-rich remnants. Olezarsen has been evaluated in patients with predominantly moderate HTG (150-499 mg/dl) and a rare genetic condition known as Familial Chylomicronemia Syndrome (FCS), with TG lowering effects of 53% and 44%, respectively, and reductions in pancreatitis among the FCS population. However, no dedicated trial has tested olezarsen in patients with severe HTG. In these two pivotal phase 3 trials, CORE -TIMI 72a (NCT05079919) and CORE2 -TIMI 72b (NCT05552326), over 1,000 patients with severe HTG will be randomized in a 2:1 fashion to either olezarsen (80 mg or 50 mg dose) or matching placebo. Patients will be treated for a total of 53 weeks and evaluated for the primary endpoint of percent change in TGs from baseline to 6 months compared to placebo. Pooled analyses of CORE and CORE2 will also assess olezarsen's effect on acute pancreatitis events and change in hepatic steatosis. Together, CORE -TIMI 72a (NCT05079919) and CORE2 -TIMI 72b (NCT05552326) are designed to establish the efficacy and safety of olezarsen in patients with severe HTG.
期刊介绍:
The American Heart Journal will consider for publication suitable articles on topics pertaining to the broad discipline of cardiovascular disease. Our goal is to provide the reader primary investigation, scholarly review, and opinion concerning the practice of cardiovascular medicine. We especially encourage submission of 3 types of reports that are not frequently seen in cardiovascular journals: negative clinical studies, reports on study designs, and studies involving the organization of medical care. The Journal does not accept individual case reports or original articles involving bench laboratory or animal research.