ARWR: PALISADE Phase 3 Results Published in NEJM…
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Phase 3 PALISADE Results Published in The New England Journal of Medicine
On September 2, 2024, Arrowhead Pharmaceuticals, Inc. (NASDAQ:ARWR) announced results for the Phase 3 PALISADE trial of plozasiran in patients with familial chylomicronemia syndrome (FCS). The results were presented in a late-breaking oral presentation at the European Society of Cardiology (ESC) Congress 2024 and also published in The New England Journal of Medicine (Watts et al., 2024). The company held an investor call on September 3, 2024 and the slides for it can be found here. Plozasiran was also recently granted Breakthrough Therapy designation by the U.S. FDA. It previously received Orphan Drug Designation and Fast Track Designation by the FDA along with Orphan Drug Designation by the European Medicines Agency.
The PALISADE trial enrolled 75 patients with persistent chylomicronemia, with or without a genetic diagnosis of FCS, who were randomized to subcutaneous plozasiran at 25 mg (n=26), 50 mg (n=24), or placebo (n=25) every three months for 12 months. Inclusion criteria included a history of multiple triglyceride (TG) measurements above 1000 mg/dL (11.3 mmol/L) along with at least one of the following: prior genetic testing diagnosis for FCS; recurrent episodes of acute pancreatitis; recurrent hospitalizations for severe abdominal pain without other explainable cause; history of childhood pancreatitis; or family history of HTG-induced acute pancreatitis. The following table shows the baseline characteristics for the patients, including the median baseline TG level of 2044 mg/dL across all cohorts.
The following graphs show the median reduction in triglycerides and level of APOC3. At the ten-month time point, the median reduction in fasting triglycerides was -80% in the 25 mg cohort, -78% in the 50 mg cohort, and -17% for the placebo cohort (P<0.001). The reduction in APOC3 was -93% in the 25 mg cohort, -96% in the 50 mg cohort, and -1% in the placebo group (P<0.001).
An important secondary efficacy endpoint compared the incidence of positively adjudicated acute pancreatitis (AP) in a pre-specified pooled analysis of the 25 mg and 50 mg plozasiran groups versus the pooled placebo group. Of the 38 suspected cases of acute pancreatitis that were referred for adjudication, nine episodes in seven patients were positively adjudicated. The results showed an 83% reduction in the risk of developing acute pancreatitis for plozasiran-treated patients compared to those treated with placebo. A total of two cases occurred in two of 50 patients (4%) receiving plozasiran versus seven cases that occurred in five of 25 patients (20%) receiving placebo (OR 0.17; P=0.03).