Olezarsen is an antisense oligonucleotide that targets apolipoprotein C-III and is indicated for the treatment of severe hypertriglyceridemia, a condition associated with a high risk of acute pancreatitis. A total of 1061 patients with severe hypertriglyceridemia were treated in two randomised, double-blind, placebo-controlled studies (CORE-TIMI 72a and CORE2-TIMI 72b). After 6 months of treatment with olesarsen, there was a significant reduction in triglyceride levels compared to placebo (p < 0.001). In addition to triglycerides, the levels of apolipoprotein C-III, remnant cholesterol and non-HDL cholesterol also decreased. The incidence of acute pancreatitis was significantly lower in patients treated with olesarsen (odds ratio 0.15; 95% confidence interval 0.05–0.40; p < 0.001). The study confirmed that olesarsen is effective and safe in lowering triglycerides and reducing the risk of pancreatitis in patients with severe hypertriglyceridemia. The duration of treatment was 53 weeks with follow-up. The research was funded by Ionis Pharmaceuticals.