Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) has reported positive topline results from the essence study of olezarsen, an investigational RNA-targeted medicine aimed at treating severe hypertriglyceridemia (SHTG). The essence study focused on individuals with moderate hypertriglyceridemia (HTG) and those diagnosed with or at risk for atherosclerotic cardiovascular disease (ASCVD).
The trial met its primary endpoint, demonstrating 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. Notably, nearly all participants were on standard lipid-lowering medicines, and the vast majority of participants reached TG levels indicative of a reduction to normal levels.
Olezarsen also met all key secondary endpoints, and the study supported the exposure database for olezarsen. The favorable safety and tolerability profile of olezarsen was demonstrated in the essence study, with the most common treatment-emergent adverse event being injection site reactions, the majority of which were mild in severity.
The essence study, a phase 3 global, multicenter, randomized, double-blind, placebo-controlled study, enrolled 1,478 participants aged 18 and older with moderate HTG. These participants 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 or 80 mg of olezarsen or placebo every 4 weeks via subcutaneous injection for 12 months.
The primary endpoint of the study was the percent change from baseline in fasting TG levels at six months compared to placebo. Key secondary endpoints included percent changes in TG levels at 12 months, the proportion of patients achieving fasting TG<150 mg/dl, and percent changes in other lipid parameters compared to placebo over the treatment period.
Olezarsen is designed to lower the body's production of apolipoprotein C-III (apoC-III), a protein produced in the liver that regulates triglyceride metabolism in the blood. It is currently being evaluated in two phase 3 clinical trials – core and core2 – for the treatment of SHTG. Olezarsen has not been approved for the treatment of SHTG by regulatory authorities, but it was recently approved in the U.S. as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS) under the trade name Tryngolza™.
The positive results of the essence study are seen as an important step in potentially bringing forward a new treatment for people with severely elevated triglycerides, expanding the potential benefit of olezarsen beyond individuals with FCS to a broader population living with SHTG. Following the FDA approval and encouraging launch of Tryngolza for individuals living with FCS, the essence study results support the broader potential of olezarsen in addressing the needs of individuals with SHTG.
The data from the pivotal phase 3 core and core2 studies evaluating olezarsen for the treatment of SHTG are expected in Q3 2025. These results will serve as the basis for a potential supplemental new drug application (sNDA) filing in SHTG by year-end.
Ionis Pharmaceuticals, Inc. has a leading pipeline in neurology, cardiology, and select areas of high patient need, and it continues to drive innovation in RNA therapies while advancing new approaches in gene editing. As a result of these announcements, the company's shares have moved 1.73% on the market, and are now trading at a price of $33.56. Check out the company's full 8-K submission here.
