Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) has announced the results from its Phase 3 PALISADE study, which investigated the efficacy of the drug plozasiran in patients with familial chylomicronemia syndrome (FCS). FCS is a rare and severe genetic condition that currently has no approved treatments in the U.S. The study met its primary and all key secondary endpoints, demonstrating significant reductions in triglycerides (TGs), apolipoprotein C-III (APOC3), and the incidence of acute pancreatitis (AP). These findings were shared today in a late-breaking oral presentation at the European Society of Cardiology (ESC) Congress 2024 and published simultaneously in The New England Journal of Medicine.
Following these positive outcomes, Arrowhead plans to file a New Drug Application with the United States Food and Drug Administration (FDA) by the end of 2024, and will also seek regulatory approvals from other global authorities.
“Patients with extremely high triglyceride levels, such as those in the PALISADE study, face a greatly increased risk of acute pancreatitis and its long-term complications, leading to a poor quality of life,” said Gerald F. Watts, D.Sc., M.D., Ph.D., Winthrop Professor of Cardio-metabolic Medicine at the University of Western Australia, Perth. “There are no currently approved therapies in the U.S. specifically for FCS, leaving physicians with few options other than limited triglyceride-lowering medications and strict dietary restrictions, which are challenging for patients and their families. Plozasiran has shown deep reductions in triglycerides and is the only investigational treatment to significantly reduce the risk of acute pancreatitis in patients with FCS in a controlled study. These results offer new hope for patients and their healthcare providers.”
Bruce Given, M.D., chief medical scientist at Arrowhead, commented, “The results from the PALISADE study and other trials within the SUMMIT program, including SHASTA in severe hypertriglyceridemia and MUIR in mixed hyperlipidemia, reinforce the potential of plozasiran as a leading treatment across various triglyceride disorders. Notably, in PALISADE, a high proportion of patients achieved triglyceride levels below the risk thresholds associated with acute pancreatitis, a crucial treatment goal. The study included both genetically confirmed FCS patients and those with symptomatic chylomicronemia suggestive of FCS, and the consistent results suggest that plozasiran’s efficacy may not depend on specific genetic variants. This supports its potential value for all patients with clinically diagnosed FCS.”
Key Results from the PALISADE Study
The PALISADE study included 75 patients with persistent chylomicronemia, with or without a genetic diagnosis. Patients were randomly assigned to receive subcutaneous plozasiran at doses of 25 mg (n=26), 50 mg (n=24), or placebo (n=25) every three months for 12 months. At the study’s start, the median triglyceride level was 2044 mg/dL. Of the participants, 44 (59%) had genetically confirmed FCS, while 31 (41%) had clinically diagnosed persistent chylomicronemia suggestive of FCS.
After ten months, the median reduction in fasting triglyceride levels (the primary endpoint) was -80% in the 25 mg plozasiran group, -78% in the 50 mg group, and -17% in the placebo group (p<0.001).
Significant reductions in triglyceride levels below the risk thresholds for acute pancreatitis were observed as early as one month after treatment began, with only modest variation over the 12-month period. The mean percentage change in triglyceride levels was consistent with the median values.
