Olezarsen has no effect on noncalcified plaque volume in patients with hypertriglyceridemia
In the CCTA substudy of Essence–TIMI 73b among patients with predominantly moderate hypertriglyceridemia, APOC3 inhibition with olezarsen substantially reduced triglycerides and remnant cholesterol but did not affect the percent change in noncalcified plaque volume from baseline to 12 months compared with placebo.
This summary is based on the publication of Marston NA, Bergmark BA, Prohaska TA, et al. - Effect of APOC3 Inhibition with Olezarsen on Coronary Atherosclerosis: Essence-TIMI 73b Imaging Study. Circulation. 2026 Mar 30. [Online ahead of print]. doi: 10.1161/CIRCULATIONAHA.126.080012
Introduction and methods
Background
Triglyceride-rich lipoproteins (TRLs) are considered atherogenic, but whether lowering these particles reduces coronary atherosclerosis remains uncertain. In the Essence–TIMI 73b trial, which included patients with predominantly moderate hypertriglyceridemia, treatment with olezarsen—an antisense oligonucleotide targeting APOC3—reduced triglycerides by ~60%, remnant cholesterol by ~70%, and apoB by ~15%, without affecting LDL-c [1].
Aim of the study
The aim of the study was to evaluate the effect of olezarsen versus placebo on coronary plaque progression in patients with hypertriglyceridemia.
Methods
This was a coronary CT angiography (CCTA) substudy within the Essence–TIMI 73b trial, comprising a total of 468 patients. Essence–TIMI 73b trial was a multicentre, randomized, double-blind, placebo-controlled trial in which patients with hypertriglyceridemia (triglycerides (TGs) ≥150 mg/dL) and increased CV risk or severe hypertriglyceridemia (TGs ≥500 mg/dL) on background lipid-lowering therapy were randomized in a 3:1 ratio to olezarsen (50 or 80 mg) or placebo administered subcutaneously every 4 weeks through month 12. Key inclusion criteria was the presence of noncalcified plaque on the baseline CCTA.
Outcomes
The primary endpoint was the placebo-adjusted percent change in noncalcified plaque volume (NCPV) from baseline to month 12. Secondary endpoints included volume changes in low-attenuation plaque and other plaque components.
Main results
- At 6 months, olezarsen reduced TGs by 63.9%, remnant cholesterol by 71.9%, and apoB by 16.0% compared with placebo, with no change in LDL-c.
- The percent change in NCPV from baseline to month 12 did not differ between olezarsen and placebo groups (placebo-adjusted least-squares mean difference: 2.98%; 95%CI: −3.4 to 9.3; P=0.36).
- There was also no difference in the percent change in low-attenuation plaque volume from baseline to month 12 between the two groups (placebo-adjusted least-squares mean difference: -68.17%; 95%CI: -266.14 to 129.81; P=0.50).
- The percent change in calcified plaque and total plaque volume from baseline to month 12 did not differ between the two groups.
- Results on NCPV were consistent across all prespecified subgroups, including age, sex, diabetes, obesity, lipid levels and baseline plaque volumes.
Conclusion
In patients with predominantly moderate hypertriglyceridemia on background lipid-lowering, APOC3 inhibition with olezarsen substantially reduced TGs and remnant cholesterol but did not affect NCPV over 12 months compared with placebo.
References
- Bergmark BA, Marston NA, Prohaska TA, et al. Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia. N Engl J Med. Oct 2 2025;393(13):1279-1291. doi:10.1056/NEJMoa2507227