#3-34E. Targeting ApoC-III: Olezarsen Reduces Pancreatitis in Severe Hypertriglyceridemia (N Engl J Med, 2026)

Can we finally prevent acute pancreatitis in patients with severe hypertriglyceridemia where conventional fibrates often fail? This episode examines the pivotal findings from two phase 3 randomized trials, CORE-TIMI 72a and CORE2-TIMI 72b, investigating the efficacy of olezarsen, an antisense oligonucleotide targeting apolipoprotein C-III mRNA. The study reports that olezarsen significantly reduced triglyceride levels by approximately 50% to 70% compared to placebo at six months. Most critically, the data revealed a striking 85% reduction in the incidence of acute pancreatitis, establishing a major clinical benefit that has historically eluded standard lipid-lowering therapies. However, when critically appraising these results, physicians should note the relatively short 12-month study duration and a dose-dependent increase in hepatic fat fraction observed in the high-dose group, which warrants careful long-term safety monitoring. For clinicians, this study is highly relevant as it suggests a potential paradigm shift in the management of severe hypertriglyceridemia, offering a new targeted option that addresses the primary clinical risk of life-threatening pancreatitis.

Citation: MARSTON, N.A., et al. Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk. N Engl J Med. 2026. DOI: 10.1056/NEJMoa2512761

Disclaimer: This audio summary is based on personal interpretation and does not guarantee the exact content of the original paper. Please refer to the original article for details.