Arrowhead Pharmaceuticals Submits FDA Application for Plozasiran to Treat Familial Chylomicronemia Syndrome

Arrowhead Pharmaceuticals, Inc. has announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for its investigational drug plozasiran, aimed at treating familial chylomicronemia syndrome (FCS). FCS is a severe and rare genetic disorder characterized by extremely high triglyceride levels, leading to an increased risk of acute pancreatitis and other long-term health complications. Currently, there are no FDA-approved treatments for this condition.

The submission of the NDA is a significant milestone for Arrowhead Pharmaceuticals, which has been working on developing new medicines using its proprietary Targeted RNAi Molecule (TRiM™) platform. The platform focuses on various therapeutic areas, including cardiometabolic, pulmonary, neuromuscular, and liver diseases. Chris Anzalone, Ph.D., President and CEO of Arrowhead, expressed the importance of this achievement, highlighting the company's commitment to using RNAi technology to make a meaningful impact on patients' lives.

Bruce Given, M.D., Chief Medical Scientist at Arrowhead, emphasized the promise of the SUMMIT program, which includes clinical studies of plozasiran. These studies have shown consistent and positive results in different patient populations with elevated triglycerides, with FCS being the most severe. Given the lack of approved therapies for FCS in the U.S., Arrowhead is dedicated to making plozasiran available to patients as quickly as possible, pending FDA review and approval.

The NDA for plozasiran is supported by data from the SUMMIT program and the Phase 3 PALISADE study, which met its primary and key secondary endpoints. The study demonstrated significant reductions in triglycerides, apolipoprotein C-III (APOC3), and the incidence of acute pancreatitis. Specifically, the plozasiran 25 mg group showed an 80% median reduction in triglycerides, and the pooled 25 mg and 50 mg group showed an 83% reduction in the risk of acute pancreatitis compared to placebo. Plozasiran has been generally well-tolerated, with the most common adverse events being abdominal pain, COVID-19, nasopharyngitis, and nausea.

The efficacy and safety results from the PALISADE study have been presented at major scientific conferences, including the American Heart Association Scientific Sessions 2024 and the European Society of Cardiology Congress 2024. The findings were also published in reputable medical journals such as Circulation and The New England Journal of Medicine.

Familial chylomicronemia syndrome is caused by various genetic mutations leading to extremely high triglyceride levels, often exceeding 880 mg/dL. These elevated levels can result in severe health issues, including acute pancreatitis, chronic abdominal pain, diabetes, liver fat accumulation, and cognitive problems. There are currently no adequate treatments for FCS in the U.S.

Plozasiran, previously known as ARO-APOC3, is an investigational RNA interference (RNAi) therapeutic designed to reduce the production of apolipoprotein C-III (APOC3). APOC3 is involved in triglyceride metabolism, and its inhibition can lower triglyceride levels, helping to restore normal lipid levels. In clinical studies, plozasiran has shown effectiveness in reducing triglycerides and other lipoproteins in patients with FCS, severe hypertriglyceridemia (SHTG), and mixed hyperlipidemia. The drug has been generally well-tolerated, with reported adverse events reflecting the underlying conditions of the study populations.

Arrowhead Pharmaceuticals has received several designations for plozasiran, including Breakthrough Therapy, Orphan Drug, and Fast Track by the FDA, and Orphan Drug by the European Medicines Agency. These designations highlight the potential of plozasiran to address unmet medical needs in patients with FCS.