Does olezarsen reduce TG levels in patients with extreme or moderate hypertriglyceridemia?
Olezarsen is a promising APOC3 ASO therapy that reduces triglycerides by ~50% without causing thrombocytopenia, though its 4-weekly administration may be a disadvantage compared to competing injectables.
Olezarsen, a GalNac-conjugated ASO targeting apoC-III, can reduce TG levels by ~ 50% in patients with extreme HTG due to familial chylomicronemia syndrome, as well as in patients with moderate HTG. Attention is now focused on whether olezarsen reduces ASCVD risk in patients with moderate and severe HTG. While olezarsen does cause elevations in liver enzymes, these changes are not clinically meaningful, and are not associated with thrombocytopenia, an issue with its predecessor, volanesorsen. The need for 4-weekly administration puts olezarsen at a disadvantage to competing injectables. Results from the CORE, CORE2, and ESSENCE phase III clinical trials in patients with severe HTG, expected in the second half of 2025, will help determine the requirement for a larger cardiovascular outcomes trial.
Hooper et al. (Sat,) studied this question.