– Up to 72% (p<0.0001) placebo-adjusted mean reduction in fasting triglycerides –
– 85% (p=0.0002) reduction in acute pancreatitis events, the first and only time achieved for the treatment of sHTG –
– Favorable safety and tolerability profile –
– sNDA submission planned by end of year –
– Ionis to host webcast today at 8:30 a.m. ET –
CARLSBAD, Calif.--(BUSINESS WIRE)--Sep. 2, 2025-- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced positive topline results from the pivotal Phase 3 CORE and CORE2 studies of olezarsen in people with severe hypertriglyceridemia (sHTG). In the studies, olezarsen demonstrated a highly statistically significant placebo-adjusted mean reduction in fasting triglycerides of up to 72% and a highly statistically significant reduction in acute pancreatitis events of 85% with favorable safety and tolerability. CORE and CORE2 make up the largest pivotal program for sHTG, with nearly 1,100 patients who were required to be on standard of care lipid-lowering therapy throughout the treatment period.
“These data are groundbreaking, demonstrating that olezarsen is the first therapy for sHTG to significantly reduce acute pancreatitis events,” said Sam Tsimikas, M.D., senior vice president, global cardiovascular development, Ionis. “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.”
The CORE and CORE2 studies met the primary endpoint, with both 80 mg and 50 mg monthly doses of olezarsen demonstrating a highly statistically significant placebo-adjusted mean reduction in fasting triglyceride levels at six months:
1. Least-squares mean. 2. Least-squares mean difference of percent reduction in fasting triglycerides. 3. P-values are based on comparison between each olezarsen group and placebo group in percent reduction in fasting triglycerides.
Additionally, the studies met the secondary endpoint of reduction in acute pancreatitis events. Olezarsen demonstrated a highly statistically significant 85% reduction in events (p=0.0002) compared to placebo. This was a prespecified analysis of pooled olezarsen groups compared to pooled placebo groups across both studies at 12 months.
“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,” said Brett P. Monia, Ph.D., chief executive officer, Ionis. “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 demonstrated a favorable safety and tolerability profile. Adverse events were generally balanced across treatment groups, and serious adverse events occurred less frequently in the olezarsen groups compared to placebo. Injection site reactions, which were mostly mild, were the most common adverse event and occurred more frequently in the olezarsen groups compared to placebo. More than 90% of patients who completed CORE and CORE2 chose to continue into the open-label extension study.
Ionis plans to submit a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration by end of year. Detailed data will be presented at an upcoming medical conference.
About the CORE and CORE2 Studies
CORE (NCT05079919; n=617) and CORE2 (NCT05552326; n=446), conducted with The TIMI Study Group, are Phase 3 global, multicenter, randomized, double-blind, placebo-controlled trials investigating the safety and efficacy of olezarsen for severe hypertriglyceridemia (sHTG). Participants aged 18 and older with triglyceride levels ≥500 mg/dL were enrolled. Participants were required to be on standard of care therapies for elevated triglycerides throughout the treatment period. At baseline, 47% and 37% of participants had baseline fasting triglycerides ≥880 mg/dL in CORE and CORE2, respectively. 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 is the percent change from baseline in fasting triglycerides at six months compared to placebo.
About Severe Hypertriglyceridemia
Severe hypertriglyceridemia (sHTG) is defined by severely high triglycerides (≥500 mg/dL) and characterized by an increased risk of acute pancreatitis and other morbidities. Considered a medical emergency, acute pancreatitis causes debilitating abdominal pain that often requires prolonged hospitalization, can lead to permanent organ damage and can become life-threatening. Preventing the first attack is key. In people with a history of acute pancreatitis episodes, the risk of future attacks is even greater. Current standard of care therapies for sHTG and lifestyle modifications (such as diet and exercise) do not sufficiently or consistently lower triglyceride levels or reduce the risks of sHTG in all patients. Approximately 3 million people are living with sHTG in the U.S., including more than 1 million who are considered high risk. High-risk sHTG includes those with triglycerides ≥880 mg/dL or triglycerides ≥500 mg/dL and a history of acute pancreatitis.
About Olezarsen
Olezarsen is an investigational RNA-targeted medicine being evaluated for the treatment of sHTG. Olezarsen is designed to lower the body's production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood. Olezarsen is approved in the U.S. as TRYNGOLZA® as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia (FCS).
About Ionis Pharmaceuticals, Inc.
For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has marketed medicines and a leading pipeline in neurology, cardiometabolic disease and select areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients.