Olezarsen cuts TGs fast

Ionis Pharmaceuticals, Inc. announced positive topline results from the Essence study of olezarsen in people with moderate hypertriglyceridemia (fasting triglycerides ≥150 mg/dL to <500 mg/dL) with or at risk for atherosclerotic cardiovascular disease (ASCVD). Nearly all the participants were on current standard of care lipid-lowering medicines. The trial met its primary endpoint with a statistically significant placebo-adjusted 61% and 58% reduction in triglyceride (TG) levels at 6 months with the 80 mg and 50 mg monthly doses, respectively (p <0.0001). Olezarsen also met all key secondary endpoints in the study. The vast majority of participants reached <150mg/dL, reflecting a reduction to normal TG levels. Olezarsen demonstrated a favorable safety and tolerability profile in the study. Ionis plans to submit an abstract for presentation at an upcoming scientific conference. Data from the pivotal Phase III CORE and CORE2 studies evaluating olezarsen for the treatment of severe hypertriglyceridemia (sHTG) are expected in Q3 2025.

The Phase III global, multicenter, randomized, double-blind, placebo-controlled study (Essence-TIMI 73b), conducted with Ionis’ research partner, The TIMI Study Group, supports the exposure database for olezarsen (NCT05610280). Essence enrolled 1,478 participants aged 18 and older with moderate hypertriglyceridemia (HTG), defined as fasting triglyceride levels ≥150 mg/dL to <500 mg/dL, who were diagnosed with or at risk for atherosclerotic cardiovascular disease (ASCVD). A small percentage of participants (9%) had fasting triglycerides ≥500 mg/dL at baseline. Participants in the study received stable and optimized standard of care lipid-lowering therapies for at least four weeks prior to screening. Participants were randomized to receive 50 mg (n=276) or 80 mg (n=832) of olezarsen or placebo (n=369) every 4 weeks via subcutaneous injection for 12 months.

The primary endpoint was the percent change from baseline in fasting TG levels at six months compared to placebo. Key secondary endpoints included percent changes in triglyceride levels at 12 months, proportion of patients who achieve fasting TG<150 mg/dL and percent changes in other lipid parameters, including apoC-III, remnant cholesterol, non-HDL-C and apoB, compared to placebo over the treatment period.

“The positive results of this study are an important step in bringing forward a potential new treatment for people with severely elevated triglycerides. Following the FDA approval and encouraging launch of TRYNGOLZA (olezarsen) for people living with familial chylomicronemia syndrome (FCS), a rare, genetic form of severely elevated TGs, these data support olezarsen’s potential to benefit the much broader population of people living with sHTG,” said Dr. Sam Tsimikas, SVP, global cardiovascular development at Ionis. “We look forward to seeing the results of our pivotal Phase 3 studies, CORE and CORE2, in Q3 2025, which will be the basis for our potential sNDA filing in sHTG by year-end.”