Medical Professionals Reference (MPR)Tryngolza Approved to Reduce Triglycerides and Pancreatitis Risk in sHTG

📋 Regulatory Action / Label Change

Adults with severe hypertriglyceridemia (TG ≥500 mg/dL) face limited pharmacologic options and meaningful acute pancreatitis risk. Olezarsen, a ligand-conjugated antisense agent targeting apolipoprotein C-III, received FDA approval June 24, 2026, becoming the first approved therapy with a labeled pancreatitis risk-reduction indication in this population.

Clinical Considerations

• In pooled CORE and CORE2 phase 3 data (N=1,061), olezarsen 80mg reduced TG by 72% and 55% respectively vs. placebo at 6 months; 86% of treated patients achieved TG below 500 mg/dL
• Olezarsen reduced acute pancreatitis event risk by 85% vs. placebo (mean rate ratio 0.15; 95% CI, 0.05–0.40; P <.001); absolute events were low (22 in 17 placebo patients vs. 7 in 5 olezarsen patients)
• Most common adverse reactions include injection site reactions and elevated liver enzymes; hypersensitivity reactions have been reported
• Liver function assessment required at baseline, following dose increase, and as clinically indicated; dose interruption or reduction should be considered for persistent enzyme elevations

Practice Applications

• Consider olezarsen for adults with TG ≥500 mg/dL inadequately controlled on diet modification, particularly those with prior or recurrent pancreatitis events
• Initiate at 50mg SC monthly; assess TG-lowering response within 3 months before escalating to 80mg for patients requiring additional reduction
• Monitor liver enzymes per label; counsel patients on low-fat diet requirement during treatment and self-injection technique prior to first dose
• Recognize the familial chylomicronemia syndrome indication as a distinct, previously approved use; the sHTG approval broadens the eligible population substantially