Treatment with olezarsen significantly reduced triglyceride levels at six months compared to placebo in patients with moderate hypertriglyceridemia and elevated cardiovascular risk, according to results of the Essence-TIMI 73b study presented during ESC Congress 2025 and simultaneously published Aug. 30 in NEJM.

In the phase 3, international, double-blind trial, Brian Bergmark, MD, FACC, et al., randomized 1,349 patients (median age 64 years; 40% women; 93% White) to six months of monthly subcutaneous injections of 50 mg olezarsen (n=254), 80 mg olezarsen (n=766) or placebo (n=329). Participants either had moderate hypertriglyceridemia and elevated cardiovascular risk or severe hypertriglyceridemia. At baseline, the median triglyceride level was 238.5 mg/dL and nearly all (96%) were receiving at least one lipid-lowering therapy. Sixty percent had diabetes.

Results at six months showed that the primary outcome, the placebo-adjusted least-squares mean change in triglycerides from baseline, was –58.4 percentage points in the 50 mg olezarsen group and –60.6 percentage points in the 80 mg group (p<0.001 for both).

Furthermore, at six months, 85% of patients in the 50 mg olezarsen group and 89% of patients in the 80 mg group had a triglyceride level of <150 mg/dL compared to 13% in the placebo group (p<0.001).

For the incidence of serious adverse events, no significant between-group difference was observed, occurring in 11% of the placebo group, 9% of the 50 mg olezarsen group and 14% of the 80 mg group. Also, no significant change in LDL-C levels from baseline were observed in any group.

This is one of the first trials testing the efficacy of olezarsen in populations with elevated triglyceride levels outside of those with rare familial chylomicronemia syndrome, write Bergmark, et al.

"Hypertriglyceridemia is frequently identified in clinical practice, yet effective therapies are lacking," they add. "Triglyceride lowering is a rapidly evolving field with several therapeutic outcomes of potential interest, including effects on lipid levels, acute pancreatitis, hepatic steatosis, and cardiovascular events."