New analysis of phase 3 data shows Sobi's olezarsen reduced acute pancreatitis events and triglycerides in a pooled CORE/CORE2 subgroup with severe hypertriglyceridemia.
Swedish Orphan Biovitrum (Sobi), a biopharmaceutical company, reported a pooled subgroup analysis from
“Acute pancreatitis is a painful and potentially life-threatening condition that often requires urgent hospitalization,” said
The finding is clinically relevant because triglyceride-associated acute pancreatitis remains a major complication of severe hypertriglyceridemia, particularly at very high triglyceride thresholds. The analysis included 455 patients from CORE and CORE2 with baseline triglycerides of at least 880 mg/dL. Compared with placebo, olezarsen 80 mg reduced triglycerides by 66% at 6 months, while olezarsen 50 mg reduced triglycerides by 59%. According to Sobi, both comparisons were statistically significant (P < .001). Overall, 85% of olezarsen-treated patients achieved triglyceride levels below 10 mmol/L.¹
CORE and CORE2 were global, multicenter, randomized, double-blind, placebo-controlled phase 3 trials conducted with the TIMI Study Group. CORE enrolled 617 participants, and CORE2 enrolled 446. Eligible adults had triglyceride levels of at least 500 mg/dL and were required to be receiving standard-of-care therapy for elevated triglycerides. Participants were randomly assigned to olezarsen 50 mg, olezarsen 80 mg, or placebo administered by subcutaneous injection every 4 weeks for 12 months. The primary end point was placebo-adjusted percent change from baseline in fasting triglycerides at 6 months.¹
In the subgroup with baseline triglycerides of at least 880 mg/dL, Sobi reported an 85% relative risk reduction in acute pancreatitis events with olezarsen vs placebo (P < .001). The company also reported an absolute reduction of 12 pancreatitis events per 100 patient-years, which corresponds to 9 patients being treated for 1 year in which 1 acute pancreatitis event would be prevented in a population similar to the subgroup studied.¹
Additional lipid changes were directionally consistent with the drug’s triglyceride-lowering mechanism. Olezarsen 80 mg and 50 mg reduced remnant cholesterol by 64% and 53%, respectively, and non–high-density lipoprotein cholesterol by 35% and 27%, respectively, according to the analysis. Sobi described the safety profile in the subgroup as favorable and similar to that observed in the broader trial population, but the company did not provide event-by-event safety data for the subgroup.¹
Severe hypertriglyceridemia is commonly defined as triglyceride levels of at least 500 mg/dL, while levels at or above approximately 880 mg/dL are associated with chylomicron accumulation and increased pancreatitis risk.¹ A real-world study cited by Sobi found increased risks of pancreatitis and cardiovascular events among adults with severe or extreme hypertriglyceridemia.² Severe hypertriglyceridemia is also recognized as an important cause of pancreatitis and a contributor to cardiometabolic risk.³ Globally, the incidence of acute pancreatitis has increased over time, with one systematic review and meta-analysis reporting an average annual increase of approximately 3% since the 1960s.⁴
Current management of severe hypertriglyceridemia generally relies on addressing secondary causes, dietary intervention,
As an RNA-targeted therapy, Olezarsen is designed to reduce hepatic production of apolipoprotein C-III, a regulator of triglyceride metabolism. The drug is approved in the United States, the European Union, and other countries as Tryngolza for adults with familial chylomicronemia syndrome. Ionis Pharmaceuticals developed olezarsen, and Sobi holds exclusive commercialization rights outside the US, except in Canada and China.¹
Regulatory review is also underway for broader severe hypertriglyceridemia use. Sobi said the European Medicines Agency validated an indication extension application in March 2026 for adults with severe hypertriglyceridemia and triglyceride levels of at least 880 mg/dL. In the US, FDA accepted a supplemental new drug application for priority review in February 2026 for severe hypertriglyceridemia defined as triglyceride levels of at least 500 mg/dL. A target action date is scheduled for June 30, 2026.¹
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