Arrowhead announces topline results from PALISADE study

Arrowhead announced topline results from the pivotal Phase 3 PALISADE study of investigational plozasiran in patients with genetically confirmed or clinically diagnosed familial chylomicronemia syndrome, or FCS, a severe genetic disease with significant unmet need and no FDA approved therapies. PALISADE successfully met the primary endpoint of lowering triglycerides and met all key secondary endpoints, including reducing the incidence of acute pancreatitis compared to placebo. The primary endpoint for the PALISADE study was placebo adjusted median change in triglycerides at Month 10. At that timepoint, patients treated with quarterly doses of 25 and 50 mg plozasiran achieved median triglyceride reductions of 80% and 78%, respectively, with a maximal reduction of 98%. At month 12, patients treated with 25 and 50 mg plozasiran achieved median triglyceride reductions of 78% and 73%, respectively, with a maximal reduction of 99%. These compared with median triglyceride reductions in placebo-treated patients of 17% at month 10 and -7% at month 12. Mean reductions in Apolipoprotein C-III at month 10 were 88% and 94% at 25 and 50 mg plozasiran, respectively. In addition to meeting the primary endpoint, plozasiran met all key secondary endpoints and demonstrated statistical significance versus placebo. There were 4 multiplicity-controlled key secondary endpoints: 1) percent change from baseline at Months 10 and 12 (averaged) in fasting triglycerides; 2) percent change from baseline at Month 10 in fasting APOC3; 3) percent change from baseline at Month 12 in fasting APOC3; 4) incidence of positively adjudicated events of acute pancreatitis during the randomized period. Plozasiran demonstrated a favorable safety profile in the PALISADE study. The number of subjects reporting treatment emergent adverse events, or AEs, were similar in plozasiran and placebo groups. Severe and serious AEs were less common with plozasiran than with placebo. The most common AEs reported were abdominal pain, COVID-19, nasopharyngitis, headache and nausea. Arrowhead plans to highlight recent data for its cardiometabolic pipeline at its June 25, 2024, Cardiometabolic event as part of the 2024 Summer Series of R&D Webinars. The company also plans to present full results from the Phase 3 PALISADE study at upcoming medical congresses and will begin to engage with global regulatory authorities about these data.