Arrowhead Announces FDA NDA Acceptance of Plozasiran
Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) announced today that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for investigational plozasiran as a treatment for familial chylomicronemia syndrome (FCS), a rare and severe genetic disorder. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of November 18, 2025, and has indicated it does not currently plan to hold an advisory committee meeting. Arrowhead also plans to submit applications for plozasiran to other regulatory authorities in 2025 to further expand its reach.
“With the acceptance of the plozasiran NDA by the FDA, we are focused on preparing for a successful commercial launch, pending FDA review and approval,” said Chris Anzalone, Ph.D., President and CEO of Arrowhead. “We are grateful to the dedicated team at Arrowhead and to the investigators, patients, and caregivers who participated in the PALISADE Phase 3 study of plozasiran. The positive results from the study offer significant hope for patients with FCS, a severe and rare disease, and we believe there is a substantial unmet medical need for effective treatments in severe hypertriglyceridemia and mixed hyperlipidemia, which we are addressing in additional Phase 3 trials as part of the SUMMIT program.”
The NDA submission is based on positive findings from the Phase 3 PALISADE study, with supporting data from the Phase 2 studies in the SUMMIT Program. The PALISADE study successfully met its primary endpoint and all key secondary endpoints. These included significant reductions in triglycerides (TGs), apolipoprotein C-III (APOC3), and the incidence of acute pancreatitis (AP).
In the PALISADE study, plozasiran demonstrated a deep and durable reduction in triglycerides, with a median change from baseline of 80% in the 25 mg dose group. Additionally, there was a statistically significant 83% reduction in the risk of acute pancreatitis when comparing the pooled 25 mg and 50 mg groups to placebo. Overall, plozasiran has been well tolerated in the clinical trials, with common treatment-emergent adverse events (TEAEs) including abdominal pain, COVID-19, nasopharyngitis, and nausea for the 25 mg dose proposed for marketing approval.
The efficacy and safety data from PALISADE were presented at the American Heart Association’s Scientific Sessions 2024 (AHA24) and were published in Circulation. The results were also shared at the European Society of Cardiology (ESC) Congress 2024 and published in The New England Journal of Medicine. These findings can be accessed on the Events and Presentations page of the Investors section of Arrowhead’s website.
About Familial Chylomicronemia Syndrome (FCS)
FCS is a rare and severe genetic disorder that leads to extremely high triglyceride (TG) levels, typically over 880 mg/dL. This condition can result in serious complications, including acute pancreatitis, chronic abdominal pain, diabetes, hepatic steatosis, and cognitive impairments. Currently, there are limited therapeutic options to adequately manage FCS, highlighting the urgent need for effective treatments.
About Plozasiran
Plozasiran, formerly known as ARO-APOC3, is a first-in-class investigational RNA interference (RNAi) therapeutic designed to reduce the production of apolipoprotein C-III (APOC3), a key regulator of triglyceride metabolism. APOC3 plays a role in elevating triglyceride levels by inhibiting the breakdown of triglyceride-rich lipoproteins (TRLs) and impeding the uptake of TRL remnants by liver receptors. By reducing APOC3 levels, plozasiran aims to lower triglyceride levels and restore normal lipid levels, offering a potential breakthrough in treating severe lipid disorders like FCS.
In clinical studies, plozasiran has shown significant reductions in triglycerides and atherogenic lipoproteins in patients with FCS, severe hypertriglyceridemia (SHTG), and mixed hyperlipidemia. The drug has been generally well tolerated, with treatment-emergent adverse events aligning with the comorbidities of the patient populations studied. Common TEAEs for the 25 mg dose, proposed for approval, included COVID-19, upper respiratory tract infections, headache, Type 2 diabetes mellitus, and abdominal pain.
Plozasiran is being studied in the SUMMIT clinical program, which includes the PALISADE Phase 3 study for FCS, the SHASTA studies for SHTG, and the MUIR and CAPITAN studies for mixed hyperlipidemia.
Plozasiran Designations and Future Plans
Plozasiran has been granted Breakthrough Therapy Designation, Orphan Drug Designation, and Fast Track Designation by the U.S. FDA, as well as Orphan Drug Designation by the European Medicines Agency. While plozasiran is still under investigation and has not been approved for any indication, these designations recognize the drug’s potential to address significant unmet medical needs.
Arrowhead has also established an Expanded Access Program (EAP) for FCS patients who may benefit from investigational plozasiran. Patients or caregivers interested in the EAP should consult with their healthcare providers to discuss potential treatment options.
About PALISADE Phase 3 Study
The PALISADE study (NCT05089084) is a Phase 3, placebo-controlled study evaluating the efficacy and safety of plozasiran in adults with genetically confirmed or clinically diagnosed FCS. The primary endpoint is the percent change in fasting triglyceride levels at Month 10. The study included 75 participants from 39 sites across 18 countries. Participants received either 25 mg or 50 mg of plozasiran, or a matching placebo, administered every three months. Following the Arrowhead randomized period, all participants who completed the study were eligible to continue in an extension phase where they received plozasiran.
Arrowhead’s commitment to advancing novel treatments for serious diseases, like FCS, is reflected in its ongoing clinical trials and the establishment of the EAP, aimed at bringing plozasiran to patients as quickly and efficiently as possible.
