FDA Accepts Arrowhead Pharma's Plozasiran Application for Familial Chylomicronemia Syndrome Treatment

On January 17, 2025, Arrowhead Pharmaceuticals, Inc., based in Pasadena, California, announced that the U.S. FDA has accepted their New Drug Application (NDA) for plozasiran, an investigational therapy aimed at treating familial chylomicronemia syndrome (FCS). This rare genetic disorder is marked by extremely high triglyceride levels, posing a significant risk of acute pancreatitis and other long-term health issues. The FDA has set a Prescription Drug User Fee Act (PDUFA) target date of November 18, 2025, for their review and has decided against holding an advisory committee meeting. Arrowhead also plans to seek approval from international regulatory bodies for plozasiran in 2025.

Chris Anzalone, Ph.D., President and CEO of Arrowhead, expressed gratitude to those involved in the Phase 3 PALISADE study of plozasiran, emphasizing the company's focus on planning a successful market launch contingent upon FDA approval. Plozasiran has demonstrated promising results not only in FCS, the most severe form of elevated triglyceride conditions, but also in broader cases of severe hypertriglyceridemia and mixed hyperlipidemia, which are being further explored in ongoing Phase 3 trials within the SUMMIT program.

The NDA submission was primarily supported by the positive outcomes of the Phase 3 PALISADE study, which met its primary and secondary endpoints. The study revealed significant reductions in triglycerides, apolipoprotein C-III (APOC3), and the occurrence of acute pancreatitis. Specifically, the 25 mg dose of plozasiran resulted in an 80% median decrease in triglycerides and an 83% reduction in the risk of acute pancreatitis compared to placebo. The treatment was generally well-tolerated, with the most common side effects being abdominal pain, COVID-19, nasopharyngitis, and nausea.

Results from the PALISADE study were shared at major scientific conferences, including the American Heart Association Scientific Sessions and the European Society of Cardiology Congress, and were published in leading medical journals. These findings highlight plozasiran's potential as a significant advancement in the treatment of FCS.

Familial chylomicronemia syndrome is primarily caused by genetic mutations leading to extremely high triglyceride levels, often exceeding 880 mg/dL. This condition results in severe symptoms, such as acute pancreatitis, chronic abdominal pain, and cognitive issues. Current treatment options for FCS are limited, highlighting the need for new therapies like plozasiran.

Plozasiran, previously known as ARO-APOC3, is an investigational RNA interference (RNAi) therapeutic targeting the reduction of APOC3, a protein that regulates triglyceride metabolism. By decreasing APOC3, plozasiran aims to lower triglyceride levels and normalize lipid profiles. Clinical studies have shown its effectiveness in reducing triglycerides and other harmful lipoproteins in patients with FCS and related conditions. The drug has been generally well-tolerated, with reported side effects reflecting the pre-existing health conditions of study participants.

Arrowhead is also conducting the SUMMIT program, which includes several studies on plozasiran for various lipid disorders. The drug has received several designations from the FDA, such as Breakthrough Therapy and Orphan Drug, as well as from the European Medicines Agency. Although investigational, plozasiran shows potential as a new treatment option for FCS and similar disorders.

Arrowhead Pharmaceuticals is committed to developing RNAi-based therapies that address challenging diseases by targeting the genes responsible for them, utilizing their extensive RNA chemistry portfolio and delivery systems. This approach aims to achieve rapid and significant gene silencing, offering hope for patients with rare and severe conditions.