NDA Submitted for Plozasiran
Arrowhead Pharmaceuticals, Inc. announced that it submitted a New Drug Application (NDA) to the FDA for investigational plozasiran for the treatment of familial chylomicronemia syndrome (FCS), a severe and rare genetic disease which currently has no FDA approved treatments
Arrowhead also intends to submit applications for approval of investigational plozasiran for the treatment of patients with FCS to additional regulatory authorities in 2025.
“The NDA submission for investigational plozasiran represents an important milestone for Arrowhead as we advance multiple potential new medicines developed using our proprietary Targeted RNAi Molecule (TRiMTM) platform for patients in diverse therapeutic areas including cardiometabolic, pulmonary, neuromuscular, and liver diseases,” said Chris Anzalone, Ph.D., President and CEO at Arrowhead. “We believe in the potential of RNAi to make a meaningful impact on patients and this first NDA submission is the culmination of over 15 years of innovation and commitment by so many talented Arrowhead employees and the investigators, patients, and caregivers that helped make our vision a reality.”
Bruce Given, M.D., chief medical scientist at Arrowhead, added, “The SUMMIT program of clinical studies of plozasiran has achieved promising and consistent results in various patient populations representing multiple points on the spectrum of elevated triglycerides. FCS represents the most severe end of the spectrum in which many patients have a very poor quality of life and are at high risk of developing acute pancreatitis, which can be life threatening. There are currently no approved therapies in the U.S. to treat FCS, so we are working tirelessly to get plozasiran to patients as quickly as possible, pending FDA review and approval.”
The NDA submission is supported by the SUMMIT program of clinical studies of plozasiran and positive findings in the Phase III PALISADE study. 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.
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 no therapeutic options that can adequately treat FCS in the US.
Citation: Plozasiran for Managing Persistent Chylomicronemia and Pancreatitis Risk. Authors: Gerald F. Watts, D.Sc., M.D., Ph.D., Robert S. Rosenson et al. Published September 2, 2024N Engl J Med 2025;392:127-137DOI: 10.1056/NEJMoa2409368VOL. 392 NO. 2
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