{"id":"6483e543f190","type":"article","url":"https://hartvaat.nl/2024/05/16/olezarsen-bij-familiaire-chylomicronemie-nejm-fase-3/","title":"Olezarsen bij familiaire chylomicronemie: NEJM fase 3","title_en":"Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":[],"journal":"The New England journal of medicine","doi":"10.1056/NEJMoa2400201","source_url":"https://doi.org/10.1056/NEJMoa2400201","authors":["Erik S G Stroes","Veronica J Alexander","Ewa Karwatowska-Prokopczuk","Robert A Hegele","Marcello Arca","Christie M Ballantyne","Handrean Soran","Thomas A Prohaska","Shuting Xia","Henry N Ginsberg","Joseph L Witztum","Sotirios Tsimikas"],"significance":9,"published":"2024-05-16","source_date":"2024-05-16","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/lpa-meten-wanneer-waarom/"],"congress":"","summary_en":"This NEJM trial demonstrated that olezarsen, an antisense oligonucleotide targeting APOC3, dramatically reduced triglyceride levels and virtually eliminated acute pancreatitis episodes in patients with familial chylomicronemia syndrome. The results represent a transformative therapy for this severe, previously intractable genetic condition.","created":"2026-07-03T10:30:56Z","updated":"2026-07-03T13:29:58Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"NEJM-trial toonde dat olezarsen (antisense tegen APOC3) het pancreatitisrisico drastisch vermindert bij familiaire chylomicronemie door spectaculaire triglyceridenverlaging. Het middel biedt de eerste effectieve therapie voor deze zeldzame genetische aandoening.","abstract_original":"BACKGROUND: Familial chylomicronemia syndrome is a genetic disorder associated with severe hypertriglyceridemia and severe acute pancreatitis. Olezarsen reduces the plasma triglyceride level by reducing hepatic synthesis of apolipoprotein C-III. METHODS: In a phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with genetically identified familial chylomicronemia syndrome to receive olezarsen at a dose of 80 mg or 50 mg or placebo subcutaneously every 4 weeks for 49 weeks. There were two primary end points: the difference between the 80-mg olezarsen group and the placebo group in the percent change in the fasting triglyceride level from baseline to 6 months, and (to be assessed if the first was significant) the difference between the 50-mg olezarsen group and the placebo group. Secondary end points included the mean percent change from baseline in the apolipoprotein C-III level and an independently adjudicated episode of acute pancreatitis. RESULTS: A total of 66 patients underwent randomization; 22 were assigned to the 80-mg olezarsen group, 21 to the 50-mg olezarsen group, and 23 to the placebo group. At baseline, the mean (±SD) triglyceride level among the patients was 2630±1315 mg per deciliter, and 71% had a history of acute pancreatitis within the previous 10 years. Triglyceride levels at 6 months were significantly reduced with the 80-mg dose of olezarsen as compared with placebo (-43.5 percentage points; 95% confidence interval [CI], -69.1 to -17.9; P<0.001) but not with the 50-mg dose (-22.4 percentage points; 95% CI, -47.2 to 2.5; P = 0.08). The difference in the mean percent change in the apolipoprotein C-III level from baseline to 6 months in the 80-mg group as compared with the placebo group was -73.7 percentage points (95% CI, -94.6 to -52.8) and between the 50-mg group as compared with the placebo group was -65.5 percentage points (95% CI, -82.6 to -48.3). By 53 weeks, 11 episodes of acute pancreatitis had occurred in the placebo group, and 1 episode had occurred in each olezarsen group (rate ratio [pooled olezarsen groups vs. placebo], 0.12; 95% CI, 0.02 to 0.66). Adverse events of moderate severity that were considered by a trial investigator at the site to be related to the trial drug or placebo occurred in 4 patients in the 80-mg olezarsen group. CONCLUSIONS: In patients with familial chylomicronemia syndrome, olezarsen may represent a new therapy to reduce plasma triglyceride levels. (Funded by Ionis Pharmaceuticals; Balance ClinicalTrials.gov number, NCT04568434.)."}