Sobi Reports 85% Lower Pancreatitis Risk with Olezarsen in sHTG

Late-breaking Phase 3 data from the CORE and CORE2 studies showed olezarsen sharply lowered triglycerides and reduced acute pancreatitis risk in patients with severe hypertriglyceridemia, strengthening the therapy’s regulatory momentum in the U.S. and Europe.

Sobi reported pooled Phase 3 data showing olezarsen (marketed as Tryngolza) reduced the relative risk of acute pancreatitis by 85% in patients with severe hypertriglyceridemia (sHTG). The late-breaking analysis combined results from the pivotal CORE (NCT05079919) and CORE2 studies (NCT05552326) and was presented at the European Atherosclerosis Society Congress 2026 in Athens, Greece.

High-Risk Subgroup Outcomes

The analysis focused on 455 patients with baseline triglyceride levels ≥880 mg/dL, a threshold strongly associated with pancreatitis risk. After six months, patients receiving olezarsen 80 mg achieved a placebo-adjusted triglyceride reduction of 66%, while the 50 mg dose reduced levels by 59% (P<0.001 for both). Most treated patients (85%) reduced triglyceride levels below 10 mmol/L, a clinically significant target endorsed by European guidelines to lower pancreatitis risk.

Mechanism and Prior Approval

Olezarsen is an RNA-targeted therapy that inhibits hepatic production of apolipoprotein C-III (apoC-III), a key regulator of triglyceride metabolism. Elevated apoC-III drives triglyceride accumulation and chylomicron persistence, increasing pancreatitis risk. The therapy is already approved for familial chylomicronemia syndrome (FCS), and the new findings expand its potential role in broader sHTG populations.

Unmet Need in Severe Hypertriglyceridemia

Severe hypertriglyceridemia remains a leading cause of pancreatitis, with limited treatment options beyond lifestyle modification and conventional lipid-lowering therapies such as fibrates, omega-3 fatty acids, and statins. These treatments often fail to achieve guideline-recommended triglyceride thresholds, highlighting the need for more targeted approaches.

Pancreatitis Risk Reduction

Beyond triglyceride lowering, investigators reported reductions in remnant cholesterol and non-HDL cholesterol across both dosing groups. The pooled analysis showed an absolute reduction of 12 pancreatitis events per 100 patient-years, translating to a number needed to treat of nine patients for one year to prevent one event. Safety findings remained consistent with the broader trial population.

Expert Commentary

Børge Nordestgaard of Copenhagen University Hospital emphasized the clinical importance of rapidly lowering triglyceride levels in patients at high risk of pancreatitis.

Sobi Chief Medical Officer Lydia Abad-Franch said the findings support a preventive treatment strategy as pancreatitis incidence continues to rise.

Regulatory Path Ahead

Regulatory momentum for olezarsen continues to build. Earlier this year, the European Medicines Agency validated an indication extension application for sHTG, while the U.S. FDA accepted a supplemental NDA under Priority Review, with a target action date of June 30, 2026. The Priority Review shortens the FDA review timeline for the supplemental application. The MHRA has also approved olezarsen (Tryngolza) for adults with familial chylomicronemia syndrome (FCS).

Olezarsen was originally developed by Ionis Pharmaceuticals, while Sobi holds commercialization rights outside the U.S., Canada, and China.

Reference

New analysis shows Tryngolza® (olezarsen) reduced acute pancreatitis by 85% and triglycerides by 66% in severe hypertriglyceridemia | Sobi