Sobi's olezarsen reduces acute pancreatitis risk by 85% in severe hypertriglyceridemia

Sobi (STO: SOBI) has reported that olezarsen (Tryngolza) reduced the relative risk of acute pancreatitis by 85% and lowered triglycerides by 66% in a pooled subgroup of patients with severe hypertriglyceridemia, the data supporting a supplemental regulatory filing that carries a US FDA action date of June 30, 2026. Sobi is aiming to add the molecule's original 2024 approval as a treatment for familial chylomicronemia syndrome (FCS)

The analysis drew from the Phase III CORE (n=617) and CORE2 (n=446) trials, both randomized, double-blind, placebo-controlled studies conducted with the TIMI Study Group. The subgroup reported here included 455 patients with baseline triglycerides at or above 880 mg/dL (~10 mmol/L), a threshold that European Atherosclerosis Society and European Society of Cardiology guidelines identify as requiring urgent intervention. At six months, patients on olezarsen 80 mg showed a placebo-adjusted triglyceride reduction of 66% (P < 0.001); those on the 50 mg dose achieved a 59% reduction (P < 0.001). In total, 85% of olezarsen-treated patients reached triglyceride levels below 10 mmol/L. The acute pancreatitis relative risk reduction of 85% translated to an absolute reduction of 12 events per 100 patient-years, with a number needed to treat of nine patients over one year to prevent one event. The 80 mg and 50 mg doses also reduced remnant cholesterol by 64% and 53%, respectively, and non-HDL-C by 35% and 27%. The safety profile in this subgroup was consistent with the broader trial population, with no new signals identified. The data were presented as a late-breaking abstract at the European Atherosclerosis Society 2026 Congress in Athens.

Olezarsen is an antisense oligonucleotide that targets apoC-III mRNA in hepatocytes, reducing the protein's inhibitory effect on lipoprotein lipase and thereby accelerating triglyceride clearance. The standard-of-care landscape for severe hypertriglyceridemia remains anchored to fibrates and omega-3 formulations — agents approved on the basis of triglyceride lowering alone, with no prospective randomized data demonstrating a reduction in acute pancreatitis events. The most mechanistically proximate approved agent is Arrowhead Pharmaceuticals' Redemplo (plozasiran), an siRNA targeting the same apoC-III pathway, though its current US approval is limited to familial chylomicronemia syndrome. Cross-trial comparisons are limited by differences in patient populations, study designs, and follow-up duration. The US FDA has accepted a supplemental new drug application for olezarsen in severe hypertriglyceridemia under Priority Review, with a target action date of June 30, 2026; the European Medicines Agency validated an indication extension application in March 2026 for patients with triglycerides at or above 880 mg/dL.

---

This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/

---

Spot something wrong? Report an issue with this article