Olezarsen Cuts Triglyceride Levels at 6 Months in Essence Study

Olezarsen significantly cut mean triglyceride levels compared with placebo for people with moderate hypertriglyceridemia (HTG) at risk for atherosclerotic cardiovascular disease (ASCVD) in new topline results from the Essence study.1

Announced by Ionis Pharmaceuticals, Inc., on May 19, 2025, olezarsen at 80 mg and 50 mg monthly doses achieved a statistically significant ~60% reduction in triglycerides at six months, with most patients returning to normal levels (<150 mg/dL).

“The positive results of this study are an important step in bringing forward a potential new treatment for people with severely elevated triglycerides,” said Sam Tsimikas, MD, senior vice president of global cardiovascular development at Ionis.1 “Following the US Food and Drug Administration (FDA) approval and encouraging launch of [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 severe HTG (sHTG).”

The FDA recently approved olezarsen (TRYNGOLZA), marking the first-ever FDA-approved therapy to significantly reduce triglyceride levels and acute pancreatitis events in adults with FCS when used in conjunction with an appropriate diet (≤20 grams of daily fat).2

Triglyceride levels ≥500 mg/dL represent a sign of sHTG, and patients remain at risk for potentially life-threatening acute pancreatitis and ASCVD despite current standards of care. Individuals with levels ≥880 mg/dL exhibit a greater risk of acute pancreatitis, including those with FCS.3

In the Phase 3, global, multicenter, randomized, double-blind, placebo-controlled Essence trial, 1478 participants aged ≥18 years with moderate HTG (fasting triglyceride levels, ≥150 mg/dL to <500 mg/dL) and with or at risk for ASCVD were enrolled for analysis. Nearly 9% had fasting triglyceride levels ≥500 mg/dL at baseline.1

Participants received optimized standard of care lipid-lowering therapies for ≥4 weeks before screening. The population was 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.

At the primary endpoint, olezarsen demonstrated a statistically significant placebo-adjusted 61% and 58% reduction in triglyceride levels at 6 months with 80 and 50 mg monthly doses, respectively (P <.0001). Olezarsen met all key secondary endpoints, including percent changes in triglycerides at 12 months, the proportion of patients who achieve fasting triglyceride <150 mg/dL, and percent changes in other lipid parameters.

Safety and tolerability of olezarsen were confirmed in the trial, with the most common treatment-emergent adverse reactions being mild injection site reactions in the olezarsen group. In the announcement, Ionis indicated pivotal data from the Phase 3 CORE and CORE2 trials assessing olezarsen for sHTG are expected in Q3 2025.1

“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,” Tsimikas added.1

References

1. Ionis announces positive topline results from Essence Study of Olezarsen in people with moderately elevated triglycerides. Ionis Pharmaceuticals, Inc. May 19, 2025. Accessed May 19, 2025. https://ir.ionis.com/news-releases/news-release-details/ionis-announces-positive-topline-results-essence-study-olezarsen.

2. Iapoce C. Olezarsen earns first-ever FDA approval for familial chylomicronemia syndrome. HCP Live. December 20, 2024. Accessed May 19, 2025. https://www.hcplive.com/view/olezarsen-earns-first-ever-fda-approval-for-familial-chylomicronemia-syndrome.

3. Bashir B, Ferdousi M, Durrington P, Soran H. Pancreatic and cardiometabolic complications of severe hypertriglyceridaemia. Curr Opin Lipidol. 2024;35(4):208-218. doi:10.1097/MOL.0000000000000939