Ionis Pharmaceuticals, Inc. announced positive topline results from its Phase 3 Essence study, evaluating olezarsen in individuals with moderate hypertriglyceridemia (fasting triglyceride levels between ≥150 mg/dL and <500 mg/dL) who either have or are at risk for atherosclerotic cardiovascular disease (ASCVD). Most study participants were already receiving standard-of-care lipid-lowering therapies.

The trial achieved its primary endpoint, with olezarsen demonstrating a statistically significant, placebo-adjusted reduction in triglyceride levels of 61% and 58% at six months for the 80 mg and 50 mg monthly doses, respectively (p < 0.0001). Olezarsen also met all key secondary endpoints, with the majority of participants achieving triglyceride levels below 150 mg/dL — the threshold for normal — and showing improvements in other lipid parameters. The investigational therapy was well-tolerated, with a favorable safety profile. The most commonly reported treatment-emergent adverse events were injection site reactions, which were predominantly mild.

Ionis plans to submit an abstract based on these findings for presentation at an upcoming scientific conference. Additional data from the pivotal Phase 3 CORE and CORE2 trials evaluating olezarsen in individuals with severe hypertriglyceridemia (sHTG) are expected in the third quarter of 2025.

“These positive findings represent a key milestone in advancing olezarsen as a potential treatment for patients with significantly elevated triglyceride levels,” said Dr. Sam Tsimikas, Senior Vice President of Global Cardiovascular Development at Ionis. “Following the recent FDA approval and launch of TRYNGOLZA™ (olezarsen) for familial chylomicronemia syndrome (FCS), these results further highlight the broad therapeutic promise of olezarsen in addressing severe hypertriglyceridemia. We anticipate the results from our pivotal CORE and CORE2 studies will support a supplemental NDA submission by the end of 2025.”

Essence Study Overview
The Essence (Essence-TIMI 73b) study is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial conducted in collaboration with The TIMI Study Group. A total of 1,478 participants aged 18 and older with moderate hypertriglyceridemia were enrolled. Participants were randomized to receive subcutaneous injections of either 50 mg or 80 mg of olezarsen or placebo every four weeks for 12 months, while continuing standard-of-care lipid-lowering therapy.

The primary endpoint was the percentage change in fasting triglyceride levels from baseline at six months. Key secondary endpoints included triglyceride levels at 12 months, the proportion of patients achieving fasting triglycerides below 150 mg/dL, and changes in other lipid biomarkers such as apoC-III, remnant cholesterol, non-HDL-C, and apoB.

About Hypertriglyceridemia and Olezarsen
Hypertriglyceridemia (HTG) is a condition marked by elevated triglyceride levels, with values above 150 mg/dL considered abnormal. Severe HTG (≥500 mg/dL) can increase the risk of life-threatening acute pancreatitis and ASCVD. Olezarsen is an investigational RNA-targeted therapy designed to reduce production of apoC-III, a liver-produced protein that regulates triglyceride metabolism. It is currently under investigation in two additional Phase 3 trials (CORE and CORE2) for sHTG.

Olezarsen is commercially available in the U.S. under the name TRYNGOLZA™ for the treatment of FCS, a rare and genetic form of severely elevated triglycerides.

TRYNGOLZA U.S. Indication and Safety Information
TRYNGOLZA is approved as an adjunct to diet for reducing triglycerides in adults with familial chylomicronemia syndrome (FCS). It is contraindicated in patients with known serious hypersensitivity to the drug or its components. Common side effects include injection site reactions, decreased platelet counts, and joint pain.

Source: https://ir.ionis.com/news-releases/news-release-details/ionis-announces-positive-topline-results-essence-study-olezarsen