Biogen, Stoke Therapeutics present follow-up analyses from zorevunersen studies

Biogen (BIIB) and Stoke Therapeutics (STOK) announced the presentation of longer-term follow-up analyses from the ongoing open-label extension studies of zorevunersen that support the potential of zorevunersen as a disease-modifying medicine for Dravet syndrome. These new results were presented at the 54th Child Neurology Society annual meeting. New two-year data from an analysis that was initially performed to understand the potential effects of the Phase 3 dosing regimen on cognition and behavior showed continuing improvements at two years. These results contrast with findings from a two-year natural history study in which patients with Dravet syndrome who were treated with standard of care showed minimal changes in cognition and behavior. In addition, the companies presented three-year results from analyses of Clinical and Caregiver Global Impression of Change an scales measuring overall clinical status, which complement previously presented EQ-VAS caregiver-reported quality of life improvements. Caregivers and clinicians separately reported similar improvements in overall clinical status in 95% of patients treated with zorevunersen. These data were among several analyses included in a poster presentation of data from the Phase 1/2a and ongoing OLE studies of zorevunersen. Safety and tolerability were the primary endpoints of these studies. In addition, effects on major motor seizure frequency, cognition and behavior were assessed as secondary endpoints. As previously reported, results showed substantial and durable reductions in major motor seizure frequency and improvements in multiple measures of cognition and behavior on top of a background of standard anti-seizure medicines through three years. The most substantial reductions were observed among patients who were treated with loading doses of 70mg in the Phase 1/2a study followed by maintenance doses of 45mg. This regimen is now being evaluated in the Phase 3 EMPEROR study. Eighty-one patients received at least one dose of zorevunersen and have been evaluated for safety. Zorevunersen has been generally well tolerated across the Phase 1/2a and OLE studies. Study drug related treatment emergent adverse events were observed in 30% and 53% of patients treated in the Phase 1/2a and OLE studies, respectively. The most common study drug related TEAE was CSF protein elevations reported in 14% of patients in the Phase 1/2a studies and 44% of patients in the OLE studies. CSF protein elevations occurred in 42% of patients in the Phase 1/2a studies and 86% of patients in the OLE studies. No related clinical manifestations have been observed although one patient discontinued treatment due to elevated CSF protein levels. Treatment-emergent serious adverse events were reported in 22% and 29% of patients in the Phase 1/2a and OLE studies, respectively, all of which were assessed to be unrelated to study drug except one patient who experienced SUSARs.