# Olezarsen bij ernstige hypertriglyceridemie en pancreatitisrisico

*geplaatst 2026-01-29 · Cholesterol · The New England journal of medicine · doi 10.1056/NEJMoa2512761 · https://hartvaat.nl/2026/01/29/olezarsen-bij-ernstige-hypertriglyceridemie-en-pancreatitisrisico/*

Trial onderzocht olezarsen specifiek bij ernstige hypertriglyceridemie met pancreatitisrisico. Het middel bood spectaculaire triglyceridenverlaging en pancreatitispreventie.

## English: Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk.

This trial evaluated olezarsen specifically in patients with severe hypertriglyceridemia and pancreatitis risk, demonstrating dramatic triglyceride reduction and pancreatitis prevention. The APOC3-targeted antisense therapy offers a definitive solution for this dangerous metabolic condition.

## Abstract (original, from the publication)

BACKGROUND: Patients with severe hypertriglyceridemia have an increased risk of acute pancreatitis. The efficacy and safety of olezarsen, an antisense oligonucleotide targeting apolipoprotein C-III messenger RNA, have not been established in this population. METHODS: We conducted two double-blind, randomized, placebo-controlled trials (CORE-TIMI 72a and CORE2-TIMI 72b). Patients with severe hypertriglyceridemia were assigned in a 1:1:1 ratio to receive olezarsen at a dose of 50 mg, olezarsen at a dose of 80 mg, or placebo monthly for 12 months. The primary outcome was the percent change in the triglyceride level at 6 months, reported as the difference between each olezarsen dose group and the placebo group (placebo-adjusted change). Secondary lipid outcomes included the percent change in the triglyceride level at 12 months and in apolipoprotein C-III, remnant cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol at 6 months and 12 months. Acute pancreatitis events were assessed across both trials. RESULTS: A total of 1061 patients were included in the primary analysis (617 in the CORE-TIMI 72a trial and 444 in the CORE2-TIMI 72b trial). At 6 months, the placebo-adjusted least-squares mean change from baseline in the triglyceride level was -62.9 percentage points in the olezarsen 50-mg group and -72.2 percentage points in the olezarsen 80-mg group in the CORE-TIMI 72a trial and was -49.2 percentage points in the olezarsen 50-mg group and -54.5 percentage points in the olezarsen 80-mg group in the CORE2-TIMI 72b trial (P<0.001 for all comparisons of olezarsen with placebo). Decreases in the levels of triglycerides, apolipoprotein C-III, remnant cholesterol, and non-HDL cholesterol were greater with olezarsen than with placebo (P<0.001 for all comparisons). The incidence of acute pancreatitis was lower with olezarsen than with placebo (mean rate ratio, 0.15; 95% confidence interval, 0.05 to 0.40; P<0.001). The incidence of any adverse events appeared to be similar across trial groups. Elevations in liver-enzyme levels and thrombocytopenia (platelet count, <100,000 per microliter) were more common with the 80-mg dose of olezarsen, and a dose-dependent increase in the hepatic fat fraction was noted. CONCLUSIONS: Among patients with severe hypertriglyceridemia, treatment with olezarsen led to a significantly greater reduction in the triglyceride level at 6 months and in the incidence of acute pancreatitis than placebo. (Funded by Ionis Pharmaceuticals; CORE-TIMI 72a and CORE2-TIMI 72b ClinicalTrials.gov numbers, NCT05079919 and NCT05552326.).

Auteurs: Nicholas A Marston, Brian A Bergmark, Veronica J Alexander, Thomas A Prohaska, Yu Mi Kang, Filipe A Moura, Andre Zimerman, Elaine Waldman, Julia Weinland, Sabina A Murphy, Erica L Goodrich, Shuanglu Zhang, Shuting Xia, Dan Li, Anne C Goldberg, Assen Goudev, Lina Badimon, Robert Gabor Kiss, Michal Vrablik, Daniel Gaudet, Philippe Moulin, Erik S G Stroes, Maciej Banach, Hofit Cohen, Dirk Blom, Min-Ji Charng, Børge G Nordestgaard, Stephen J Nicholls, Sotirios Tsimikas, Robert P Giugliano, Marc S Sabatine

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Bron: The New England journal of medicine, https://doi.org/10.1056/NEJMoa2512761. Bijgewerkt 2026-07-03T13:31:07Z. 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.