The US FDA has approved Tryngolza (olezarsen) — making it the first therapy demonstrated to reduce the risk of acute pancreatitis in adults with severe hypertriglyceridemia. The approval, granted to California-based Ionis Pharmaceuticals, addresses a gap that has persisted despite decades of available triglyceride-lowering agents: no prior approved medication had generated sufficient pancreatitis event data in clinical trials to establish a risk reduction claim.
Tryngolza is indicated, used alongside dietary modification, to reduce triglycerides and the risk of acute pancreatitis in adults with severe hypertriglyceridemia, defined as fasting triglyceride levels of at least 500 mg/dL. It is administered as a subcutaneous injection once monthly. The drug received both Priority Review and Breakthrough Therapy designations from the FDA, reflecting the agency’s assessment of its potential to address an unmet clinical need.
Olezarsen is an antisense oligonucleotide that targets apolipoprotein C-III (APOC3) messenger RNA in the liver, reducing APOC3 protein levels and thereby enhancing triglyceride clearance from the bloodstream. APOC3 inhibits lipoprotein lipase, the primary enzyme responsible for triglyceride hydrolysis, making it a validated target in severe hypertriglyceridemia.
Efficacy and safety data came from two randomized, double-blind, placebo-controlled Phase III trials — NCT05079919 and NCT05552326 — enrolling a combined 1,061 adults with severe hypertriglyceridemia. The average baseline triglyceride level across both trials was 1,116 mg/dL. The primary endpoint in each trial was percent change in fasting triglycerides from baseline to month 6. In the first trial, olezarsen reduced triglycerides by 63% at the 50 mg dose and 72% at the 80 mg dose versus placebo; the second trial reported reductions of 49% and 55%, respectively. An integrated analysis across both trials demonstrated a reduction in acute pancreatitis event rate in the pooled olezarsen group compared with placebo.