Plozasiran

– The New Drug Application is based on positive results from the Phase 3 PALISADE study – People living with familial chylomicronemia syndrome have extremely high triglyceride levels and a substantially higher risk of developing acute pancreatitis and associated long-term complications, including poor quality of life PASADENA, CA, USA I January 17, 2025 I Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for investigational plozasiran for the treatment of familial chylomicronemia syndrome (FCS), a severe and rare genetic disease. The FDA provided a Prescription Drug User Fee Act (PDUFA) action date of November 18, 2025, and indicated it is not currently planning to hold an advisory committee meeting. Arrowhead also intends to submit applications for approval of investigational plozasiran for the treatment of patients with FCS to additional regulatory authorities in 2025. “With the plozasiran NDA submission and FDA’s acceptance for filing complete, we are laser focused on our ongoing work to ensure an efficient and successful commercial launch this year, pending FDA review and approval. We would like to thank all Arrowhead employees and the investigators, patients, and caregivers who contributed to the PALISADE Phase 3 study of plozasiran in patients with genetically confirmed or clinically diagnosed FCS,” said Chris Anzalone, Ph.D., President and CEO at Arrowhead. “Plozasiran has achieved promising and consistent results in various patient populations representing multiple points on the spectrum of diseases caused by elevated triglycerides. FCS represents the most severe and rare end of the spectrum; however, we believe that substantial unmet medical need exists in severe hypertriglyceridemia and mixed hyperlipidemia, which we are investigating in additional Phase 3 trials as part of the SUMMIT program of clinical studies.” The clinical basis of the NDA submission is comprised of the positive findings in the Phase 3 PALISADE study with supportive confirmatory evidence from the Phase 2 clinical studies of the SUMMIT Program. PALISADE successfully met its primary endpoint and all multiplicity-controlled key secondary endpoints, including statistically significant reductions in triglycerides (TGs), apolipoprotein C-III (APOC3), and the incidence of acute pancreatitis (AP). In PALISADE, plozasiran achieved deep and durable reductions in triglycerides with a median change from baseline of 80% in the plozasiran 25 mg group and a statistically significant 83% reduction in the risk of developing acute pancreatitis compared to placebo in the pooled plozasiran 25 mg and 50 mg group. Overall, plozasiran has been generally well-tolerated to date. In the PALISADE study, the most frequently reported treatment emergent adverse events for the 25 mg dose that is proposed for marketing approval were abdominal pain, COVID-19, nasopharyngitis, and nausea. The efficacy and safety results from the PALISADE study were presented at the American Heart Association Scientific Sessions 2024 (AHA24) and simultaneously published in Circulation and presented at the European Society of Cardiology (ESC) Congress 2024 and simultaneously published in The New England Journal of Medicine . AHA24, ESC, and other plozasiran presentations may be accessed on the Events and Presentations page in the Investors section of the Arrowhead website. About Familial Chylomicronemia Syndrome Familial chylomicronemia syndrome (FCS) is a severe and rare disease often caused by various monogenic mutations. FCS leads to extremely high triglyceride (TG) levels, typically over 880 mg/dL. Such severe elevations can lead to various serious signs and symptoms including acute and potentially fatal pancreatitis, chronic abdominal pain, diabetes, hepatic steatosis, and cognitive issues. Currently, there are limited therapeutic options to adequately treat FCS. About Plozasiran Plozasiran, previously called ARO-APOC3, is a first-in-class investigational RNA interference (RNAi) therapeutic designed to reduce production of apolipoprotein C-III (APOC3) which is a component of triglyceride rich lipoproteins (TRLs) and a key regulator of triglyceride metabolism. APOC3 increases triglyceride levels in the blood by inhibiting breakdown of TRLs by lipoprotein lipase and uptake of TRL remnants by hepatic receptors in the liver. The goal of treatment with plozasiran is to reduce the level of APOC3, thereby reducing triglycerides and restoring lipids to more normal levels. In multiple clinical studies, investigational plozasiran has demonstrated reductions in triglycerides and multiple atherogenic lipoproteins in patients with familial chylomicronemia syndrome (FCS), severe hypertriglyceridemia (SHTG), and mixed hyperlipidemia. Plozasiran has been generally well tolerated to date with treatment emergent adverse events reported that generally reflect the comorbidities and underlying conditions of the study populations. Across clinical studies and study populations, the most frequently reported treatment emergent adverse events for the 25 mg dose that is proposed for marketing approval were COVID-19, upper respiratory tract infection, headache, Type 2 diabetes mellitus, and abdominal pain. Plozasiran is being investigated in the SUMMIT program of clinical studies, including the PALISADE Phase 3 study in patients with FCS, the SHASTA studies in patients with SHTG, and the MUIR and CAPITAN studies in patients with mixed hyperlipidemia. Plozasiran in the treatment of patients with FCS has been granted Breakthrough Therapy Designation, Orphan Drug Designation, and Fast Track Designation by the U.S. Food and Drug Administration and Orphan Drug Designation by the European Medicines Agency. Investigational plozasiran has not been reviewed or approved to treat any disease. About PALISADE Phase 3 Study The PALISADE study ( NCT05089084 ) is a Phase 3 placebo controlled study to evaluate the efficacy and safety of plozasiran in adults with genetically confirmed or clinically diagnosed FCS. The primary endpoint of the study is percent change from baseline in fasting TG versus placebo at Month 10. A total of 75 subjects distributed across 39 different sites in 18 countries were randomized to receive 25 mg plozasiran, 50 mg plozasiran, or matching placebo once every three months. Participants who completed the randomized period were eligible to continue in a 2-part extension period, where all participants receive plozasiran. About Plozasiran EAP Arrowhead is committed to bringing new investigational medicines to patients with serious diseases as quickly and efficiently as possible. The company has established an expanded access program (EAP) for some individuals living with FCS. As with any investigational medicine that has not been approved by regulatory authorities, investigational plozasiran may or may not be effective in treating your diagnosis or condition, and there may be risks associated with its use. If you are a patient or caregiver wishing to know more about this plozasiran EAP for FCS, please discuss this EAP and all treatment options with your treating physician. If you are a treating physician and are seeking information about the plozasiran EAP or would like to request access for a patient, please contact EAP@arrowheadpharma.com . About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit www.arrowheadpharma.com , or follow us on X (formerly Twitter) at @ArrowheadPharma , LinkedIn , Facebook , and Instagram . To be added to the Company’s email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts . SOURCE: Arrowhead Pharmaceuticals

Ionis’ antisense oligonucleotide olezarsen is now the first approved treatment for familial chylomicronemia syndrome, a rare metabolic disorder that prevents the body from breaking down fats called triglycerides. Olezarsen, to be marketed as Tryngolza, is expected to be available by the end of the year at a list price of $595,000 annually. The approval is likely to be seen as critical for FCS patients, whose main option until now has been an extremely low-fat diet. FCS affects few people in the US: about 1 to 13 per million, according to Ionis. CEO Brett Monia hopes to get a “first-mover advantage,” adding that Ionis has “built very strong relationships with the healthcare providers, the HCPs, that manage these patients in centers of excellence.” Regulators based their approval on the Phase 3 BALANCE study , in which olezarsen showed a statistically significant reduction in patients’ triglyceride levels after six months at an 80 mg dose compared to placebo, meeting a primary endpoint. Importantly, just one case of pancreatitis (a serious complication of FCS) occurred in the 80 mg olezarsen group, compared to 11 cases in the placebo group, Ionis said. Monia sees blockbuster potential in Tryngolza, if Ionis is able to eventually expand the label to a broader condition also marked by high levels of triglycerides called severe hypertriglyceridemia. Ionis expects Phase 3 data to read out in the second half of next year, with a potential FDA submission shortly after. “SHTG is the real blockbuster opportunity, with millions of people, hundreds of thousands that have been diagnosed already, and with no treatment options available,” Monia said. Ionis could soon face competition from Arrowhead, which filed for FDA approval of its experimental drug plozasiran for FCS November. Arrowhead is also recruiting in a Phase 3 trial for SHTG, according to the company’s website. “With significant first mover advantage in both populations and compelling results already demonstrated in FCS, coupled with our expectation for similarly positive data in SHTG, we believe olezarsen could be the standard of care for both disease indications,” Monia said on Ionis’ latest quarterly earnings call in November, according to an AlphaSense transcript. Tryngolza will be Ionis’ first independent launch, marking an important transition for the company. While the company has historically relied on pharma partners for commercialization, Tryngolza is one of several programs that Ionis hopes to independently launch over the next few years. “This is the final step in an evolution of the company that we started when I became the CEO in 2020 to really transform Ionis into a fully integrated commercial-stage biotech company,” Monia told Endpoints. Editor’s Note: This story has been updated to include Tryngolza’s list price.