Arrowhead Pharma Unveils Phase 3 Data on Plozasiran at ESC 2024 for Familial Chylomicronemia Syndrome

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) has announced successful results from its Phase 3 PALISADE study of the investigational drug plozasiran for treating familial chylomicronemia syndrome (FCS), a severe genetic disorder. The study met its primary and key secondary endpoints, showing significant reductions in triglycerides (TGs), apolipoprotein C-III (APOC3), and the incidence of acute pancreatitis (AP). These findings were unveiled at the European Society of Cardiology (ESC) Congress 2024 and published in The New England Journal of Medicine.

Arrowhead plans to file a New Drug Application with the FDA by the end of 2024 and will also seek regulatory approvals globally. Gerald F. Watts, a professor of Cardio-metabolic Medicine at the University of Western Australia, highlighted the promising results of plozasiran, which achieved significant reductions in triglycerides and the risk of developing acute pancreatitis in FCS patients. This is significant as there are currently no approved therapies specifically for FCS in the U.S., and existing treatment options offer minimal benefits.

Bruce Given, M.D., Chief Medical Scientist at Arrowhead, emphasized the potential of plozasiran based on the promising results from various clinical studies, including the PALISADE study. Plozasiran showed effectiveness in reducing triglyceride levels below risk thresholds associated with acute pancreatitis. The consistency of these results supports the potential of plozasiran as a valuable treatment for patients with clinically diagnosed FCS, regardless of their genetic status.

The PALISADE study involved 75 patients with persistent chylomicronemia, both with and without a genetic diagnosis. Participants were randomly assigned to receive subcutaneous plozasiran at doses of 25 mg or 50 mg, or a placebo, every three months for a year. The baseline median triglyceride level was 2044 mg/dL. By month ten, fasting triglyceride levels had decreased by 80% in the 25 mg group, 78% in the 50 mg group, and 17% in the placebo group. APOC3 levels also saw significant reductions.

A key secondary outcome was the incidence of positively adjudicated acute pancreatitis. Plozasiran resulted in an 83% reduction in the risk of developing acute pancreatitis compared to placebo. Only two cases occurred among patients receiving plozasiran, compared to seven cases in the placebo group, highlighting the drug’s efficacy.

The safety profile of plozasiran was favorable, with common adverse events including abdominal pain, COVID-19, nasopharyngitis, headache, nausea, back pain, upper respiratory tract infection, and diarrhea. Serious adverse events were more common in the placebo group. Hyperglycemia was noted in some patients but was limited to those with pre-diabetes and diabetes.

The ESC 2024 presentation by Professor Gerald Watts detailed these findings, emphasizing the significance of the PALISADE study in the context of lipid therapy. Arrowhead Pharmaceuticals plans further discussions on the data at an analyst and investor event.

Plozasiran, an RNA interference (RNAi) therapeutic, targets the reduction of APOC3, a key regulator of triglyceride metabolism. It has shown efficacy in multiple clinical studies for conditions like familial chylomicronemia syndrome, severe hypertriglyceridemia, and mixed hyperlipidemia. Plozasiran has received Orphan Drug Designation and Fast Track Designation from the FDA and Orphan Drug Designation from the European Medicines Agency.

Arrowhead Pharmaceuticals is dedicated to developing RNAi-based therapies to treat severe diseases by silencing the genes that cause them. The company's pipeline includes various clinical programs, reflecting its commitment to leveraging RNA interference technology for therapeutic purposes.

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