Olezarsen Effectively Lowers Triglycerides in High-Risk Cardiovascular Patients: Results from a Clinical Trial

A recent clinical trial has demonstrated that Olezarsen significantly reduces blood triglyceride levels in patients at elevated cardiovascular risk. The trial, presented at ESC Congress 2025 and published in the American Heart Journal, involved adults with moderate hypertriglyceridemia (150–499 mg/dL) who also had high risk factors for cardiovascular disease due to existing ASCVD, diabetes, or advanced age.

Olezarsen functions by targeting the mRNA of apolipoprotein C-III, a protein that impedes triglyceride clearance. Previous small-scale Phase II studies showed promise, and now the Phase III ESSENCE-TIMI 73b trial confirms its efficacy in a larger population. The study enrolled around 1,349 participants across North America and Europe. These patients were administered subcutaneous injections of Olezarsen at dosages of 50 mg or 80 mg every four weeks over a 12-month period.

Results indicated a substantial reduction in triglyceride levels during the trial. After six months, the least-squares mean difference in triglyceride percentage change from baseline was approximately -58.4% for the 50 mg dose and -60.6% for the 80 mg dose, both highly significant versus placebo. By 12 months, over 80% of patients treated with Olezarsen reached triglyceride levels below 150 mg/dL, a notable improvement compared to only 12.5% in the placebo group.

Additionally, Olezarsen lowered other lipoproteins, including remnant cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B, without significantly affecting LDL cholesterol levels. The safety profile was acceptable, with incident rates of serious adverse events similar across groups, although liver transaminase elevations were more frequent with Olezarsen, typically mild.

Lead investigator Dr. Brian Bergmark emphasized that Olezarsen could offer a powerful new approach for managing triglycerides in high-risk cardiovascular patients, surpassing the modest effects of existing therapies. Overall, the trial suggests that monthly Olezarsen injections could help reduce atherogenic lipoprotein levels and potentially decrease cardiovascular risk in these patients.