Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) on Tuesday released topline results from the pivotal Phase 3 CORE and CORE2 studies of olezarsen for severe hypertriglyceridemia (sHTG).
sHTG is a condition where triglyceride levels are significantly elevated, typically 500 mg/dL or higher, which is a major risk factor for acute pancreatitis.
In December 2024, the FDA approved Ionis Pharmaceuticals’ Tryngolza (olezarsen) as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS), a rare, genetic form of severe hypertriglyceridemia (SHTG) that can lead to acute pancreatitis (AP).
“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.”
“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.”
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.
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.
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.
Olezarsen demonstrated a favorable safety and tolerability profile.
Ionis plans to submit a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration by the end of the year.
Most recently, the FDA approved Ionis Pharmaceuticals’ Dawnzera (donidalorsen) for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older.
William Blair notes that there was considerable investor debate heading into the topline data on the degree of magnitude of pancreatitis event risk reduction and need for statistical significance. Analyst Myles Minter says, “We view this resoundingly positive outcome as clearly settling this debate.”
“Taken together, we view these data as the best-case scenario for Ionis and substantially exceeding our expectations,” the analyst further wrote.
Price Action: IONS stock is trading higher by 31.35% to $56.00 at last check Tuesday.
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