September 2, 2025
BIOINVEST NEWS: IONIS (IONS)
Ionis (IONS) – IONS Hits Homerun with Phase III Olezarsen CORE Data for High TGs & Acute Pancreatitis
IONS had great news today when they reported positive topline data from the Phase III CORE (n=617) and CORE2 (n=446) trials of Olezarsen in severe hypertriglyceridemia (sHTG), where there was a statistically significant placebo-adjusted mean reduction in fasting triglycerides (TG) of up to 72%, the primary endpoint, at the 80mg dose in CORE, and, importantly, a statistically significant reduction in acute pancreatitis (AP) events of 85% (p=0.0002) across the two studies. While positive TG data was largely expected by investors, we see the stock reaction today as driven by the AP benefit, as it is a key economic advantage for commercial uptake and access/reimbursement. Now, the focus will shift to the potential 2H26 launch via a monthly autoinjector, where management first plans to prioritize prescribers, across cardiologists, endocrinologists and lipidologists, to high-risk patients, of which there are one million in the US. The Olezaesen data is excellent and opens up a potential blockbuster opportunity for the company and also significantly increases the odds of a premium takeover.
sHTG is a disease where triglyceride levels are significantly elevated, typically 500 mg/dL or higher, which is a major risk factor for acute pancreatitis. 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 very good safety. The most common side effects were mild injection site reactions; 90% of participants continued onto an open-label extension study for long-term monitoring.
Importantly, both CORE trials 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. Coming into the topline data release there was considerable investor debate on the degree of magnitude of pancreatitis event risk reduction and need for statistical significance. In our view, this is a resoundingly positive outcome and opens up a potential blockbuster opportunity for the company.
IONS plans to submit the sNDA to the FDA by YE (leading to a potential launch in 2H26 (4Q assuming standard review); global filings in 2026) and present the detailed data at an upcoming medical conference in 2H25. On the prevalent population, IONS framed that there are >3mn people with sHTG in the US, including one million people with high-risk sHTG (TGs 880mg/dL and 500mg/dL with a history of AP). IONS underscored the importance of the AP data, which it expects will be key for KOLs given the severity of AP events. The company plans to launch olezarsen as a monthly autoinjector and first target high-risk sHTG patients, where the relevant physicians include cardiologists, endocrinologists and lipidologists. Management’s launch strategy further includes cardiometabolic account specialists to focus on target high-risk Docs at launch and marketing resources to complement its field teams. The Olezaesen data is excellent and opens up a potential blockbuster opportunity for the company and also significantly increases the odds of a premium takeover.