Arrowhead Pharmaceuticals announced results from the Phase 3 PALISADE study of investigational plozasiran in patients with familial chylomicronemia syndrome, a severe and rare genetic disease which currently has no approved treatments in the U.S. PALISADE successfully met its primary endpoint and all multiplicity-controlled key secondary endpoints, including statistically significant reductions in triglycerides, apolipoprotein C-III, and the incidence of acute pancreatitis. These data were presented today in a late-breaking oral presentation at the European Society of Cardiology Congress 2024 and simultaneously published in The New England Journal of Medicine. Based on these positive findings from the PALISADE study, Arrowhead intends to file a New Drug Application with the United States Food and Drug Administration by year-end 2024 and plans to seek regulatory approval with additional global regulatory authorities thereafter.
In PALISADE, 75 patients with persistent chylomicronemia, with or without a genetic diagnosis, were randomly assigned to receive subcutaneous plozasiran at 25 mg or 50 mg or placebo every three months for 12 months. At baseline, the median triglyceride level was 2044 mg/dL. Forty-four patients had genetically confirmed FCS and 31 patients had clinically diagnosed persistent chylomicronemia suggestive of FCS. At month ten, the median reduction from baseline in the fasting triglyceride level was -80% in the 25 mg plozasiran group, -78% in the 50 mg plozasiran group, and -17% in the placebo group.
Marked reductions in the median triglyceride level below guideline-directed risk thresholds associated with acute pancreatitis occurred as early as one month after trial initiation and showed modest variation throughout the 12-month blinded treatment period. The mean percentage change in triglyceride level was similar to median values. At month ten, APOC3 was significantly reduced with median reductions of -93% in the 25 mg plozasiran group, -96% in the 50 mg plozasiran group, and -1% in the placebo group. The final alpha-controlled secondary efficacy end point compared the incidence of positively adjudicated acute pancreatitis in a pre-specified pooled analysis of the 25 mg and the 50 mg plozasiran groups versus the pooled placebo group.
Among the 38 suspected cases of acute pancreatitis that were referred for adjudication, nine episodes in seven patients were positively adjudicated. Plozasiran demonstrated statistical significance for this endpoint, with patients receiving plozasiran achieving an 83% reduction in the risk of developing acute pancreatitis versus placebo. A total of two cases occurred in two of 50 patients receiving plozasiran, and seven cases occurred in five of 25 patients receiving placebo. Plozasiran demonstrated a favorable safety profile in the PALISADE study.
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