Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) announced today the results of the Phase 3 PALISADE study evaluating investigational plozasiran in patients with familial chylomicronemia syndrome (FCS), a rare and severe genetic condition with no approved treatments in the U.S. The study met its primary endpoint and all key secondary endpoints, including significant reductions in triglycerides (TGs), apolipoprotein C-III (APOC3), and the incidence of acute pancreatitis (AP). These findings were presented at the European Society of Cardiology (ESC) Congress 2024 and published in The New England Journal of Medicine.
Following these positive results, Arrowhead plans to submit a New Drug Application to the FDA by the end of 2024 and will pursue regulatory approvals in other regions.
“Patients with extremely high triglyceride levels, like those in the PALISADE study, face an elevated risk of acute pancreatitis and its long-term complications, severely affecting their quality of life. Currently, no approved therapies specifically target FCS in the U.S., leaving physicians with limited options,” said Dr. Gerald F. Watts, Winthrop Professor of Cardio-metabolic Medicine at the University of Western Australia. “Plozasiran’s significant reduction in triglycerides and the risk of acute pancreatitis in this study is highly promising for patients with FCS.”
Dr. Bruce Given, Chief Medical Scientist at Arrowhead, noted, “We are encouraged by the results from the SUMMIT program, including the PALISADE study for FCS, which suggests plozasiran could be a best-in-class therapy across a range of triglyceride disorders. The consistency of results, irrespective of genetic status, highlights plozasiran’s potential value for patients with clinically diagnosed FCS.”
Key Results from PALISADE:
- In the trial, 75 patients with persistent chylomicronemia, with or without a genetic diagnosis, were randomized to receive subcutaneous plozasiran at 25 mg (n=26), 50 mg (n=24), or placebo (n=25) every three months for 12 months. The median baseline triglyceride level was 2044 mg/dL, with 59% of patients having genetically confirmed FCS and 41% having clinically diagnosed persistent chylomicronemia suggestive of FCS.
- At month ten, median reductions in fasting triglycerides (primary endpoint) were -80% in the 25 mg group, -78% in the 50 mg group, and -17% in the placebo group (p<0.001).
- Significant reductions in APOC3 were observed, with median reductions of -93% in the 25 mg group, -96% in the 50 mg group, and -1% in the placebo group (p<0.001).
- A pre-specified pooled analysis showed an 83% reduction in the risk of acute pancreatitis in patients receiving plozasiran compared to placebo. Two cases occurred in the plozasiran group (4%) versus seven cases in the placebo group (20%) (odds ratio, 0.17, p=0.03).
Arrowhead’s findings indicate that plozasiran could offer a much-needed therapeutic option for patients with FCS, significantly reducing triglyceride levels and the risk of acute pancreatitis, improving overall patient outcomes in this challenging condition.
