Photo Credit: Nemes Laszlo

Olezarsen lowered triglycerides by about 50% at month 6 compared with placebo in the BRIDGE-TIMI73a trial and reduced other markers of atherogenic risk.

The antisense oligonucleotide olezarsen lowered triglycerides by about 50% at month 6 compared with placebo in the BRIDGE-TIMI73a trial. Moreover, the agent led to clinically relevant reductions in other markers of atherogenic risk.

Reducing triglyceride-rich lipoproteins remains an unmet clinical need. Loss-of-function mutations in the APOC3 gene have been shown to lower triglyceride levels. Olezarsen is an antisense oligonucleotide targeting APOC3 mRNA. The BRIDGE-TIMI 73a trial (NCT05355402) assessed the efficacy and safety of olezarsen in patients with moderate hypertriglyceridemia (150 to <500 mg/dL) and elevated cardiovascular risk or in patients with severe hypertriglyceridemia (≥500 mg/dL).¹ All patients were already receiving standard-of-care anti-lipid medication. The participants received either 50 mg or 80 mg olezarsen or placebo, subcutaneously every 4 weeks.

At month 6, the placebo-adjusted change in triglyceride concentrations of patients treated with 50 mg olezarsen (n=58) was -49.3% (95% CI -59.0 to -39.5; P<0.001) (primary study endpoint). The corresponding number in the 80 mg group was -49.3% (95% CI -62.7 to 43.3; P<0.001). Moreover, Apo-C-III protein levels dropped by -64.2% in patients in the 50 mg group and by -73.2% in the 80 mg group (P<0.001 for each comparison). “If you actually want to reduce a patient’s risk for a heart attack or stroke, you would like to see a reduction in apolipoprotein B, and we did see that in this study, which is very encouraging,” the study’s principal investigator, Brian Bergmark, MD, commented.

85.7% of patients treated with 50 mg and 93.3% of patients treated with 80 mg achieved a triglyceride goal of less than 150 mg/dl at 6 months. This was 11.8% in the placebo group (P<0.001 for both comparisons). As Dr. Bergmark pointed out, this triglyceride effect was greater than is possible with currently available treatments. Another advantage of olezarsen is its meaningful reductions in apolipoprotein B and non-high-density lipoprotein cholesterol.

No major safety concerns emerged in the study or the follow-up period. Additional trials of olezarsen that include patients with severe hypertriglyceridemia are ongoing.

Medical writing support was provided by Dr Susanne Kammerer.
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