Ionis’ Olezarsen Achieves Phase III Success in Severe Hypertriglyceridemia

Ionis Pharmaceuticals announced positive topline results from its Phase III CORE and CORE2 trials of olezarsen, an RNA-targeted therapy for severe hypertriglyceridemia (sHTG). Conducted globally with the TIMI Study Group, the placebo-controlled trials enrolled about 1,100 patients aged 18 or older with fasting triglycerides ≥500mg/dL, all maintained on standard lipid-lowering therapy.

Olezarsen demonstrated a placebo-adjusted mean reduction in fasting triglycerides of up to 72% and achieved the primary endpoint of significant triglyceride reduction at six months. It also reduced acute pancreatitis events by 85% over 12 months, meeting a key secondary endpoint. Both 50mg and 80mg doses were administered subcutaneously every four weeks, showing a favorable safety and tolerability profile.

Following trial completion, more than 90% of participants transitioned into an open-label extension. Ionis plans to submit a supplemental new drug application (sNDA) to the FDA by year-end, aiming to position olezarsen as a transformative treatment option for sHTG.

06-09-2025