Olezarsen Demonstrates Favorable Reductions in Triglycerides for Hypertriglyceridemia

Olezarsen showed statistically significant mean reductions in fasting triglycerides of up to 72% compared with the placebo for patients with severe hypertriglyceridemia (sHTG), according to new topline results from the phase 3 CORE (NCT05079919) and CORE2 (NCT05552326) studies. Furthermore, the drug showed significant reductions in acute pancreatic events of 85% with favorable safety and tolerability.¹

Olezarsen significantly reduces triglycerides and acute pancreatitis events, offering new hope for patients with severe hypertriglyceridemia. | Image Credit: Siarhei - stock.adobe.com

“These data are groundbreaking, demonstrating that olezarsen is the first therapy for sHTG to significantly reduce acute pancreatitis events,” Sam Tsimikas, MD, senior vice president of global cardiovascular development at Ionis, said in a news release. “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 both studies, investigators evaluated the efficacy of olezarsen compared with the placebo on the change in fasting triglycerides. In CORE, investigators included 6178 patients who received either the study drug or the placebo for a treatment period of 53 weeks. In CORE2, there were 446 individuals included for a 53-week period. Both studies lasted approximately 78 weeks, including a 12-week screening period, a 53-week treatment period, and a 13-week posttreatment evaluation. Patients could transition to the open-label extension study for up to 1 year of treatment.^2,3

The primary outcome of both studies was the change from baseline in fasting triglycerides compared with the placebo. Secondary end points included percent change in fasting Apolipoprotein C-III, Remnant Cholesterol and Fasting Non-High-Density Lipoprotein-Cholesterol, proportion of patients who achieved fasting triglyceride of less than 500 mg/dL (5.65 mmol/L), proportion of patients who achieved fasting triglyceride of less than 880 mg/dL (10 mmol/L), adjudicated acute pancreatitis even rate during the treatment period, and absolute change in hepatic fat fraction.^2,3

Both studies met the primary end point with both the 80 mg and 50 mg doses of the drug at 73% and 63%, respectively, compared with 0.5% for the placebo in CORE and 68% and 63%, respectively, compared with 14% for the placebo in CORE2.¹

Furthermore, investigators noted that olezarsen met the secondary endpoint of reduction in acute pancreatitis events. The safety and tolerability of the drug were also favorable.¹

“Building on our success in familial chylomicronemia syndrome, the exceptional CORE and CORE2 results position Ionis to set a new treatment standard for the many people with sHTG who are at risk of debilitating acute pancreatitis attacks,” Brett P. Monia, PhD, CEO of Ionis, said in the news release.¹ “If approved, olezarsen for sHTG will mark our third independent launch in under two years and our first launch in a prevalent population, marking a major step forward in delivering transformative care to those who need it most.”

Olezarsen was approved as the first-ever treatment for adults living with familial chylomicronemia syndrome as an adjunct to diet.⁴

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REFERENCES

1. Olezarsen significantly reduces triglycerides and acute pancreatitis events in landmark pivotal studies for people with severe hypertriglyceridemia (sHTG). News release. Ionis Pharmaceuticals. September 2, 2025. Accessed September 5, 2025. https://ir.ionis.com/news-releases/news-release-details/olezarsen-significantly-reduces-triglycerides-and-acute

2. A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia. ClinicalTrials.gov identification: NCT05079919. Updated January 29, 2025. Accessed September 5, 2025. https://www.clinicaltrials.gov/study/NCT05079919?term=olezarsen&rank=8

3. A Study of Olezarsen Administered Subcutaneously to Participants With Severe Hypertriglyceridemia. ClinicalTrials.gov identification: NCT05552326. https://www.clinicaltrials.gov/study/NCT05552326?term=olezarsen&rank=7

4. Tryngolza (olezarsen) approved in US as first-ever treatment for adults living with familial chylomicronemia syndrome as an adjunct to diet. News release. Ionis Pharmaceuticals. December 19, 2024. Accessed September 5, 2025. https://ir.ionis.com/news-releases/news-release-details/tryngolzatm-olezarsen-approved-us-first-ever-treatment-adults