Olezarsen, a new investigational drug that blocks production of apolipoprotein C-III (apoC3), may cut triglyceride levels nearly in half, as well as lower apoC3 and apolipoprotein B (apoB) levels in patients with hypertriglyceridemia (HTG) and high cardiovascular risk, according to the results of the BRIDGE-TIMI 73a study presented during a Late-Breaking Clinical Trial session at ACC.24 and published simultaneously in the New England Journal of Medicine.

The phase 2b, double-blind study, conducted at 24 sites across the U.S. and Canada, randomly assigned 154 patients (median age 62 years, 42% women, 92% White) with moderate HTG (150-<500 mg/dL) plus high cardiovascular risk or severe HTG (≥500 mg/dL) to one of two doses of olezarsen (50 mg or 80 mg) or placebo for a subcutaneous injection every four weeks for up to 49 weeks in addition to standard-of-care lipid treatment. Their median TG level at the start of the study was 241.5 mg/dL.

Results showed that the primary endpoint of percent change in TG from baseline to six months was reduced by 49.3% with the 50 mg dose of olezarsen and 53.1% with the 80 mg dose, compared with 7.8% with placebo (p<0.001 for both). For the secondary endpoint of percent change in apoC3 at 12 months, there was an average reduction of 64.2% and 73.2%, respectively, with the 50 mg and 80 mg doses of olezarsen. Levels of apoB were reduced by about 18% with both doses. A high proportion of patients taking olezarsen achieved a TG <150 mg/dL at six months: 85.7% and 93.3% with the 50 mg and 80 mg doses, respectively. All reductions in lipid levels were maintained for 12 months. Clinically significant adverse effects were uncommon.

Brian Bergmark, MD, FACC, principal investigator of the study, noted that the difference between the decrease in TG levels between the 50 mg dose and the 80 mg was relatively small, but the 80 mg dose resulted in a larger reduction in apoC3. In addition, the reduction in levels of apoB is of interest because of its presence in all lipid particles that contribute to atherosclerosis. "If you actually want to reduce a patient's risk for a heart attack or stroke, you would like to see a reduction in apoB, and we did see that in this study, which is very encouraging," he said.

"Treatments to reduce high triglycerides are an unmet clinical need," said Bergmark. "Based on our study's results, we can say that the drug worked and appeared to be safe." Phase 3 studies of olezarsen, including in patients with severe hypertriglyceridemia, are underway.