Ionis Pharmaceuticals has reported encouraging topline outcomes from the randomised Phase III CORE and CORE2 trials of the investigational RNA-targeted therapy, olezarsen, in those with severe hypertriglyceridemia (sHTG).
The placebo-controlled, double-blind, multi-centre, global trials revealed a substantial placebo-adjusted mean decrease in fasting triglycerides of up to 72% and a significant decrease in acute pancreatitis events by 85%, while maintaining a favourable tolerability and safety profile.
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
Carried out with the TIMI Study Group, these trials for sHTG involved around 1,100 subjects.
Those aged 18 years or above with triglyceride levels of 500mg/dL or higher were involved in these trials, and the participants are mandated to be on standard lipid-lowering therapy throughout the trial time.
The company noted that 47% of subjects in CORE and 37% in CORE2 had baseline fasting triglyceride levels of 880mg/dL or higher.
They were randomly assigned and injected either 50mg or 80mg of the therapy or a placebo every four weeks subcutaneously over 12 months.
US Tariffs are shifting - will you react or anticipate?
Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis.
By GlobalDataMeasuring the percentage change in fasting triglycerides at six months from baseline against placebo is the primary goal.
Both studies achieved their primary endpoint, showing a statistically significant decrease in fasting triglyceride levels at the six-month mark for both therapy dosages.
Furthermore, the secondary endpoint of reducing acute pancreatitis events was also met, with an 85% decrease in events for the therapy against placebo over 12 months.
Following the completion of these studies, more than 90% of the subjects opted to continue in the open-label extension trial.
The company is preparing for a supplemental new drug application (sNDA) submission to the US Food and Drug Administration (FDA) by the end of this year.
Ionis Pharmaceuticals global cardiovascular development senior vice-president Sam Tsimikas said: “Despite current standard of care and lifestyle changes, people with sHTG – who could have triglyceride levels reaching into the thousands – remain vulnerable to unpredictable and life-threatening acute pancreatitis attacks.
“These results reinforce our confidence that olezarsen has the potential to change the sHTG treatment paradigm.”
In June 2025, Ionis dosed the first subject in the Phase III REVEAL study of ION582, aimed at treating Angelman syndrome.
