Olezarsen benefits hypertriglyceridemia patients at high cardiovascular risk

Treatment with olezarsen in patients with hypertriglyceridemia and elevated cardiovascular risk results in substantial reductions in triglyceride, apolipoprotein B, and non–high-density lipoprotein (HDL) cholesterol levels, while having no major safety signals, according to data from the phase IIb Bridge–TIMI 73a study.

The trial included 154 patients (median age 62 years, median triglyceride level 241.5 mg/dL) either with moderate hypertriglyceridemia (triglyceride level, 150–499 mg/dL) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg/dL). These patients were randomly assigned to receive monthly subcutaneous olezarsen at 50 or 80 mg or matching placebo.

The primary outcome was the percent change in the triglyceride level from baseline to 6 months. Key secondary outcomes included changes in APOC3, apolipoprotein B, non-HDL cholesterol, and low-density lipoprotein (LDL) cholesterol concentrations.

At 6 months, triglyceride levels decreased by 49.3 percentage points in the 50-mg olezarsen group and by 53.1 percentage points in the 80-mg group relative to placebo (p<0.001 for both comparisons).

Likewise, both doses of olezarsen showed superiority to placebo in terms of reducing the levels of APOC3, apolipoprotein B, and non-HDL cholesterol. There was no significant change in the LDL cholesterol level.

As for safety, the risks of adverse events and serious adverse events were comparable across the three groups. Clinically meaningful hepatic, renal, or platelet abnormalities were rare, with similar risks in the three groups.