Arrowhead Pharmaceuticals has announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for plozasiran, an investigational treatment for familial chylomicronemia syndrome (FCS). This submission marks a significant step toward addressing the unmet medical needs of patients with this rare genetic disorder characterized by severely elevated triglyceride levels and a heightened risk of acute pancreatitis. There are currently no FDA-approved therapies for FCS. The company plans to seek approval for plozasiran in other markets in 2025.
The NDA is supported by data from the Phase 3 PALISADE study, a clinical trial designed to evaluate the efficacy and safety of plozasiran in patients with FCS. The PALISADE study met its primary endpoint, demonstrating a statistically significant reduction in triglyceride levels compared to placebo. Key secondary endpoints were also met, indicating a decrease in the risk of acute pancreatitis, a severe and potentially life-threatening complication of FCS.
Plozasiran is developed using Arrowhead's proprietary Targeted RNAi Molecule (TRiM™) platform. The drug is designed to lower the production of apolipoprotein C-III, a key regulator of triglyceride metabolism. By reducing apolipoprotein C-III levels, plozasiran aims to lower triglyceride levels and mitigate the associated risks of FCS.
Management Perspectives
"This NDA submission is the culmination of over 15 years of innovation at Arrowhead," said Chris Anzalone, Ph.D., President and CEO of Arrowhead Pharmaceuticals. Bruce Given, M.D., Chief Medical Scientist, emphasized the urgent need for an effective treatment for FCS patients, noting the poor quality of life many patients experience due to the disease's severity.
Regulatory Designations and Access Programs
The FDA has granted plozasiran several designations, including Breakthrough Therapy Designation, Orphan Drug Designation, and Fast Track Designation. These designations are intended to expedite the development and review of drugs that address serious conditions and unmet medical needs. Arrowhead has also established an expanded access program (EAP) to provide plozasiran to eligible FCS patients before it becomes commercially available.
Financial Context
Arrowhead Pharmaceuticals reported a net loss of $170.8 million for its fiscal 2024 third quarter, with cash and investments totaling $436.7 million. The company has secured a $400 million loan from Sixth Street to support its pipeline development. Arrowhead is also advancing its central nervous system (CNS)-targeted RNA interference (RNAi) programs, with plans to initiate a Phase 1 clinical trial of ARO-ATXN2 for spinocerebellar ataxia 2 (SCA2) in the first quarter of 2025. Additionally, the company aims to file a Clinical Trial Application for ARO-MAPT, a new siRNA being developed for Alzheimer's disease, in the second half of 2025.
