Key Points:
- Olezarsen, an anti-sense oligonucleotide targeting APOC3 mRNA, is approved to lower triglycerides (TG) in adults with rare familial chylomicronemia, but its safety and efficacy in a broader populations is unknown.
- In Essence-TIMI 73b, olezarsen significantly reduced TG by ~60% compared with placebo in patients with moderate or severe hypertriglyceridemia and elevated CV risk.
- There was also improvement in other atherogenic lipid measurements with no major safety concerns apart from mild to moderate injection site reactions.
Olezarsen is a subcutaneously administered ligand-conjugated antisense oligonucleotide that inhibits hepatic production of ApoC-III, which delays TG-rich lipoprotein clearance. By suppressing ApoC-III, olezarsen enhances TG clearance and lowers serum TG levels. While it is approved for rare hypertriglyceridemia syndromes, its safety and efficacy in broader patient populations are uncertain.
On August 30th 2025, the results of “Essence-TIMI 73b: Olezarsen in patients with hypertriglyceridemia at high cardiovascular risk” were presented at the European Society of Cardiology Congress in Madrid, Spain.
The trial randomized 1478 patients with TG levels between 150-500 mg/dL at high cardiovascular risk (defined as established atherosclerotic cardiovascular disease or age ≥ 55 years with diabetes) or those with severe hypertriglyceridemia (≥ 500mg/dL) to receive olezarsen 50mg monthly, olezarsen 80mg monthly, or placebo. The primary endpoint was percent change in TG at 6 months. Secondary endpoints included changes in other lipid components.
Overall, 254 participants received the 50mg dose, 766 received the 80mg dose and 329 received placebo. At 6 months, olezarsen significantly reduced TG levels: placebo-adjusted percent changes were -58.4% (95% CI -65.1, -51.7; p <0.001) for the 50mg dose and -60.6% (95% CI -67.1, -54.0; p<0.001) for the 80mg dose. More than 85% of participants treated with olezarsen achieved a TG <150mg/dL at 6 months, compared to 12.5% of placebo.
Olezarsen also significantly reduced ApoC-III, non-HDL-C, VLDL-C remnant cholesterol, and ApoB, while increasing in HDL-C at 6 months. There was no difference in in serious adverse events or drug discontinuation between the groups, although non-severe injection site reactions were more common with olezarsen than placebo.
Dr. Brian Bergmark, MD, of Brigham and Women’s Hospital in Boston, MA, concluded: “In patients with moderate hypertriglyceridemia and heightened CV risk, olezarsen reduced TG level by approximately 60%, [a greater effect] than is possible with current standard of care therapies, with no major safety concerns. These findings support the efficacy and safety of olezarsen for TG lowering in a broad population of patients.”
