ACC.24 – Olezarsen is an antisense oligonucleotide (ASO) targeting mRNA for APOC3. What are findings of a phase 2b trial with two doses of olezarsen in patients with predominantly moderate hypertriglyceridemia and elevated CV risk?

This summary is based on the presentation of Brian Bergmark, MD (Boston, MA, US) at the ACC.24 Scientific Session – Efficacy and Safety Of Olezarsen In Patients With Hypertriglyceridemia And High Cardiovascular Risk: Primary Results Of the BRIDGE -TIMI 73a Trial

Introduction and methods

Elevated levels of triglycerides and triglyceride-rich lipoproteins are associated with increased CV risk. Therefore, there is a need for therapeutic agents to lower triglycerides and triglyceride-rich lipoproteins.

In the phase 2b BRIDGE-TIMI 73a trial, 154 patients with either moderate hypertriglyceridemia (triglycerides 150-500 mg/dL) and increased CV risk or severe hypertriglyceridemia (≥500 mg/dL) were enrolled. They were randomized in a 1:1 ratio to cohort A, in which patients were further randomized in a 3:1 ratio to olezarsen 50 mg SC every 4 weeks or placebo, or to cohort B, in which patients were further randomized in a 3:1 ratio to olezarsen 80 mg SC every 4 weeks or to placebo.

The primary endpoint was the % change in triglcyerides from baseline to 6 months. Secondary endpoints included % changes in lipid parameters at 6 months and assessment of safety (ALT/AST, renal function, platelets).

Main results

• At 6 months, the placebo-adjusted % change from baseline in triglyceride levels was -49.3% (95%CI: -59.0 to -39.5) in the olezarsen 50 mg group and -53.1% (95%CI: -62.9 to -43.4) in the olezarsen 80 mg group. 
• Placebo-adjusted LSM % changes at 6 months for the olezarsen 50 mg group were: -64.2% for ApoC-III, -46.2% for VLDL-c, -46.6% for remnant cholesterol, -18.2% for ApoB, -25.4% for non-HDL-c, +39.6% for HDL-c, +14.5% for ApoA1, -9.9% for LDL-c and -9.8% for total cholesterol. Similar findings were observed with 80 mg olezarsen.
• In patients with moderate hypertriglyceridemia at baseline, 85.7% (P<0.001) of patients in the olezarsen 50 mg group reached TG<150 mg/dL at 6 months. This was 93.3% of patients in the olezarsen 80 mg group and 11.8% of patients in the placebo group.
• There were no major safety concerns.

Conclusion

In patients with either moderate hypertriglyceridemia and increased CV risk or severe hypertriglyceridemia, olezarsen 50 mg or 80 mg monthly administered significantly reduced levels of triglycerides. In addition, dr. Bergman noted that olezarsen resulted in reductions in apoB and non-HDL-c, markers of atherogenic risk. - Our reporting is based on the information provided at the ACC.24 Scientific Session -

The findings of this study were simultaneously published in N Engl J Med