Costello Syndrome

Ionis is set to continue handling the therapy’s commercialisation in the US. Credit: Ionis Pharmaceuticals, Inc. Ionis Pharmaceuticals has entered a licence agreement with Sobi in which the latter obtains exclusive rights to commercialise olezarsen intended for familial chylomicronaemia syndrome (FCS) and severely elevated triglycerides. Sobi’s rights cover nations outside Canada, China and the US. Ionis will continue handling the therapy’s commercialisation in the US, while Theratechnologies has the licence for commercialisation in Canada. Sobi will handle upcoming regulatory filings and commercialisation in the agreed territories, excluding the US geographies. Sobi will make upfront, milestone-based payments to Ionis and up to mid-20% tiered royalties on yearly net sales. Olezarsen, known by the tradename Tryngolza, gained approval from the Food and Drug Administration in December 2024 as an adjunct to diet for decreasing triglycerides in the adult population with FCS. The European Medicines Agency is reviewing the therapy, with approval expected in 2025 to treat FCS. Olezarsen is also being evaluated for severe hypertriglyceridemia in the Phase III CORE, CORE2 and ESSENCE clinical trials, with ESSENCE data anticipated in the middle of 2025 and CORE and CORE2 later in the year. As the European commercialisation partner of Ionis for Waylivra (volanesorsen), Sobi is set to utilise its current market expertise, allowing the launch of olezarsen for FCS. FCS results from impaired enzyme lipoprotein lipase function. Ionis Pharmaceuticals CEO Brett Monia stated: “This agreement enables us to advance our goal of making olezarsen available to patients globally while focusing our independent commercialisation efforts in the US. “With anticipated data from our robust sHTG Phase III programme in 2025, we are enthusiastic about the potential for olezarsen to also address the significant medical need in this more prevalent patient population in addition to FCS.”

– Agreement enables olezarsen to reach people living with conditions associated with elevated triglycerides across the world – – Ionis will continue to independently commercialize TRYNGOLZA™ (olezarsen) in the U.S. – CARLSBAD, CA, USA I March 26, 2025 I Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced that it has entered into a license agreement under which Sobi® receives exclusive rights in countries outside the U.S., Canada and China to commercialize olezarsen as a potential treatment for familial chylomicronemia syndrome (FCS) and severely elevated triglycerides. Ionis will continue to independently commercialize olezarsen in the U.S. Olezarsen was approved by the FDA in December 2024 under the tradename TRYNGOLZA™ as an adjunct to diet to reduce triglycerides in adults with FCS – the first and only treatment in the U.S. for this rare, debilitating genetic disease. Olezarsen is currently under review by the European Medicines Agency (EMA) with a potential approval anticipated for the treatment of FCS this year. Sobi will be responsible for future regulatory submissions and commercialization in ex-U.S. geographies except Canada and China. Olezarsen was licensed to Theratechnologies for commercialization in Canada. “We look forward to deepening our long-standing partnership with Sobi and our shared commitment to improving the lives of people living with conditions marked by severely elevated triglycerides,” said Brett P. Monia, Ph.D., chief executive officer, Ionis. “This agreement enables us to advance our goal of making olezarsen available to patients globally, while focusing our independent commercialization efforts in the U.S. With anticipated data from our robust sHTG Phase 3 program in 2025, we are enthusiastic about the potential for olezarsen to also address the significant medical need in this more prevalent patient population in addition to FCS.” Sobi® (STO: SOBI) brings deep commercialization expertise for both rare and more prevalent conditions, with operations in more than 30 countries, and is committed to bringing olezarsen to as many global patients as possible. As Ionis’ current European commercialization partner for Waylivra® (volanesorsen), which is the only medicine approved for FCS in Europe, Sobi will leverage existing market expertise and distribution channels to enable an effective olezarsen launch in FCS and future potential expansion to a broader population with severely elevated triglycerides, assuming approval. Under the agreement, Ionis receives an upfront payment, additional payments based on achievement of milestones and a tiered royalty of up to mid-20% range on annual net sales. “We are thrilled to continue our collaboration with Ionis and bring this potential new medicine to patients if approved,” said Guido Oelkers, chief executive officer, Sobi. “This will enable us to further leverage our combined strengths and to continue to deliver our commitment to provide innovative medicines that transform the lives of people with rare and debilitating diseases.” In addition to FCS, Ionis is evaluating olezarsen for the treatment of severe hypertriglyceridemia (sHTG) in three Phase 3 clinical trials – CORE , CORE2 and ESSENCE . Data from ESSENCE are expected mid-2025 and data from CORE and CORE2 are expected in the second half of 2025. About Familial Chylomicronemia Syndrome (FCS) FCS is a rare, genetic disease characterized by extremely elevated triglyceride levels. It is caused by impaired function of the enzyme lipoprotein lipase (LPL). Because of limited LPL production or function, people with FCS cannot effectively break down chylomicrons, lipoprotein particles that are 90% triglycerides. FCS is estimated to impact up to approximately 3,000 people in the U.S. People living with FCS are at high risk of acute pancreatitis (AP) in addition to other chronic health issues such as fatigue and severe, recurrent abdominal pain. People living with FCS are sometimes unable to work, adding to the burden of disease. About Severe Hypertriglyceridemia (sHTG) sHTG is a disease categorized by triglyceride levels of 500 mg/dL and above. It develops due to primary (genetic) and secondary causes including diet and lifestyle, other medical conditions and certain medications. More than three million people are currently estimated to live with sHTG in the U.S. People living with sHTG are at risk of potentially life-threatening acute pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD). Olezarsen has not been reviewed or approved for the treatment of severe hypertriglyceridemia (sHTG) by any regulatory authority. About TRYNGOLZA™ (olezarsen) TRYNGOLZA™ (olezarsen) was approved by the U.S. Food and Drug Administration as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). TRYNGOLZA is an RNA-targeted medicine designed to lower the body’s production of apoC-III, a protein produced in the liver that is a key regulator of triglyceride metabolism. It is the only treatment currently indicated in the U.S. for FCS, a potentially life-threatening disease. For more information about TRYNGOLZA, visit TRYNGOLZA.com . IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS TRYNGOLZA is contraindicated in patients with a history of serious hypersensitivity to TRYNGOLZA or any of the excipients in TRYNGOLZA. Hypersensitivity reactions requiring medical treatment have occurred. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions (including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills and myalgias) have been reported in patients treated with TRYNGOLZA. Advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to promptly seek medical attention and discontinue use of TRYNGOLZA if hypersensitivity reactions occur. ADVERSE REACTIONS The most common adverse reactions (incidence >5% of TRYNGOLZA-treated patients and >3% higher frequency than placebo) were injection site reactions, decreased platelet count and arthralgia. Please see full Prescribing Information for TRYNGOLZA. About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has six marketed medicines and a leading pipeline in neurology, cardiology, 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. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter), LinkedIn and Instagram . SOURCE: Ionis Pharmaceuticals

iStock, JHVEPhoto Despite securing the industry’s first approval for familial chylomicronemia syndrome, BMO Capital Markets believes that Tryngolza’s regulatory triumph will not be a significant positive for Ionis. Instead, the firm is focusing on olezarsen’s readout in severe hypertriglyceridemia, a much larger market. The FDA on Thursday cleared the U.S.’s first treatment for the rare disease familial chylomicronemia syndrome: Ionis Pharmaceuticals’ RNA-targeting therapy olezarsen, which will be marketed under the brand name Tryngolza. Ionis expects to make Tryngolza available in the U.S. before the year ends, according to its announcement. Affecting up to around 3,000 people in the U.S., familial chylomicronemia syndrome (FCS) is a rare, genetic form of severe hypertriglyceridemia (sHTG), or excessively high triglyceride levels. Patients with FCS are unable to effectively break down fats and remove triglycerides from the blood, resulting in several chronic health problems and complications such as fatigue, abdominal pain and acute pancreatitis. The last can prove fatal. Tryngolza, an antisense oligonucleotide, addresses the triglyceride surplus in FCS patients by targeting and binding to the apolipoprotein C-III mRNA, thereby tagging it for destruction. As a result, Tryngolza lowers levels of apoC-III, a protein that under normal circumstances suppresses the action of the lipoprotein lipase enzyme. Through this mechanism of action, Tryngolza boosts the clearance of triglycerides from the blood. With the FDA’s approval, Tryngolza can now be used in adult FCS patients as an adjunctive intervention to dietary adjustments, according to its label . The drug is designed to be delivered via subcutaneous injection. Ionis backed Tryngolza’s application with data from the Phase III Balance study, which showed that an 80-mg dose of the treatment lowered triglyceride levels by a mean of 42.5%, adjusted for placebo. Over 12 months of follow-up, Tryngolza also led to a “clinically meaningful reduction” in acute pancreatitis events, according to Ionis’ announcement on Thursday. In a statement, CEO Brett Monia called Tryngolza’s approval “a transformational moment” for FCS patients and their families. “For the first time, adults with FCS can now access a treatment that substantially reduces triglycerides and the risk of debilitating and potentially life-threatening acute pancreatitis.” In a Friday note to investors, William Blair analysts highlighted the “relatively clean front page” for Tryngolza’s label, which has no “adverse event warnings besides potential hypersensitivity reactions.” Additionally, Ionis’ RNA-targeting therapy “received a broad label, permitting treatment of patients through both genetic and/or clinical diagnosis,” according to the analysts. BMO Capital Markets, meanwhile, is more measured in its optimism. In a Thursday investor note, BMO analysts wrote that “we don’t expect FCS to be a significant opportunity” for Ionis, given the small market in the U.S. and impending competition from Arrowhead’s plozasiran. The firm projects $341 million in peak sales for Tyngolza in this indication. Instead, the BMO analysts focused on sHTG, which is a much broader indication and “can confer a meaningfully larger opportunity” for olezarsen. A Phase III readout in sHTG is expected in the second half of 2025, according to the analysts, adding that BMO anticipates “stronger [triglyceride] lowering vs. FCS.” BMO expects olezarsen’s peak sales in sHTG to be five or six times higher than in FCS.