FDA Approves Ionis's 'Tringolza' as First-in-Class Therapy for Preventing Pancreatitis in Severe Hypertriglyceridemia Patients
First Therapy Approved to Reduce Risk of Pancreatitis
The U.S. Food and Drug Administration (FDA) has approved olezarsen (brand name: Tryngolza), developed by Ionis Pharmaceuticals (IONS), as the first treatment to reduce the risk of acute pancreatitis in adult patients with severe hypertriglyceridemia (sHTG). Tryngolza is an antisense oligonucleotide (ASO) rare disease drug that effectively reduces blood triglyceride levels by targeting and inhibiting the production of apolipoprotein C-III (apoC-III) in the liver, which is responsible for inhibiting triglyceride breakdown. Unlike existing treatments that only control triglyceride levels, Tryngolza is a significant advancement as it is the first option to directly prevent and manage the occurrence of life-threatening acute pancreatitis. This approval follows the 2024 approval for the treatment of familial chylomicronemia syndrome (FCS), a rare genetic disorder, and represents an expansion of indications and entry into a larger patient population.
Breakthrough Results from CORE and CORE2 Phase 3 Clinical Trials
The medical basis for this approval is clearly demonstrated by the global Phase 3 CORE and CORE2 clinical trials, published in the New England Journal of Medicine (NEJM). In a study involving a total of 1,063 severe patients, Tryngolza significantly reduced fasting triglyceride levels by up to 72% compared to the placebo group (p<0.0001). Most notably, the drug reduced the incidence of acute pancreatitis, a life-threatening complication, by as much as 85% compared to the placebo group. These excellent clinical results provide strong evidence that Tryngolza can be established as a key treatment that contributes not only to improving metabolic indicators but also to reducing hospitalization rates and improving patient survival.
Competitive Landscape with Arrowhead and Other Pipeline Candidates
The global market for triglyceride and apoC-III targeted therapies is currently dominated by a two-way competition between Tryngolza and plozasiran (brand name: Redemplo), an siRNA therapy developed by Arrowhead Pharmaceuticals (ARWR). While plozasiran has also been approved for the treatment of FCS in the United States and Europe and has received Breakthrough Therapy Designation for sHTG, Tryngolza has secured a first-mover advantage by being the first to be approved for the prevention of acute pancreatitis in sHTG. Furthermore, unlike Waylivra, which had previous issues with side effects, Tryngolza has demonstrated a high safety profile by alleviating concerns about severe thrombocytopenia, which is expected to facilitate rapid adoption in clinical practice. The global market for the treatment of severe hypertriglyceridemia, which has a high unmet need, is estimated to grow from approximately $2 billion in 2024 to approximately $4.6 billion by 2035, with an annual growth rate of more than 10%, making early market dominance crucial.
Accelerated Global Commercialization through Multinational Partnerships
Ionis is directly conducting exclusive sales of Tryngolza in the United States, while also successfully concluding strategic licensing and commercialization agreements with multinational pharmaceutical companies to expand its global reach. In Canada, the rights were transferred to Theratechnologies (THTX) in December 2024 for a non-refundable upfront payment of $10 million and milestone payments of up to $12.75 million, and the company is preparing for approval by Health Canada. In addition, in March 2025, the rights to sell Tryngolza in Europe and Asia, excluding the United States, Canada, and China, were transferred to Sobi, securing milestone payments and royalties of up to the mid-20% range. This diversified partnership strategy is driving Ionis's transformation from a research and development-focused biotech company to a mid-sized company with a portfolio of commercial-stage pipeline products, enhancing its financial structure and corporate value.
This approval is based on clinical data from Phase 3 trials that showed an 85% reduction in the risk of acute pancreatitis in patients with severe hypertriglyceridemia (sHTG), and it is medically significant in that it provides the first preventive option in a market with a high unmet medical need. From an investor's perspective, Ionis (IONS), which holds exclusive rights in the United States, and Sobi and Theratechnologies (THTX), which have acquired global sales rights, are expected to show strong short-term revenue growth, which will further enhance financial stability through the inflow of milestone payments, including the $10 million upfront payment for the Canadian contract. In the medium to long term, it will be a catalyst for establishing a strong First-in-Class position in the global sHTG market, which is expected to grow to approximately $4.6 billion by 2035. In a situation where Arrowhead (ARWR)'s plozasiran is aiming to enter the sHTG market as a later-stage siRNA-based competitor, the early market leadership and excellent safety data secured by Ionis will serve as a formidable defense in the market share competition.