Stoke reports ‘substantial’ reductions in seizure frequency with zorevunersen

Stoke Therapeutics (STOK) announced new data from an analysis of nine patients treated with an initial 2 or 3 doses of 70mg, followed by 45mg maintenance dosing in the Phase 1/2a and open-label extension studies of zorevunersen. Substantial and durable reductions in convulsive seizure frequency were observed in these patients who received zorevunersen on top of the best available anti-seizure medicines. In addition, patients treated in the OLE studies showed continuous improvements in multiple measures of cognition and behavior with ongoing treatment through 2 years. Zorevunersen was generally well tolerated across the studies. Together, these data support the company’s proposed Phase 3 registrational study regimen and its efforts to develop zorevunersen as a disease-modifying medicine for the treatment of Dravet syndrome. Previously reported end-of-Phase 1/2a study data from patients treated with two or three doses of 70mg of zorevunersen showed substantial and sustained reductions in convulsive seizure frequency of 85% at 3 months and 74% at six months post-last dose. The company is now reporting data for the nine patients who continued treatment with at least two doses of 45mg of zorevunersen in the OLE study. These patients sustained at least a 50% median reduction from baseline at each month of the OLE and demonstrated an 87% median reduction at month eight, the latest timepoint for which data have been assessed for these nine patients. Patients experienced continuous improvements in multiple measures of cognition and behavior as measured by the Vineland-3 through 2 years of treatment with ongoing maintenance dosing in the OLEs. Additional improvements were indicated within the first nine months of treatment among patients in the Phase 1/2a ADMIRAL study. At the time of the analysis, 81 patients had been treated with zorevunersen in the Phase 1/2a studies. Seventy-four patients who completed the Phase 1/2a studies and were eligible enrolled in the OLEs. As of June 2024, 82% remained in the OLE studies. In the Phase 1/2a studies: 30% of patients experienced a treatment-emergent adverse event that was related to study drug. The most common were CSF protein elevations and procedural vomiting; and 22% of patients had a treatment-emergent serious adverse event. These events were assessed as unrelated to study drug except for the previously reported case of one patient who experienced Suspected Unexpected Serious Adverse Reactions. Across the studies, one patient discontinued treatment due to study drug. As previously reported, this patient discontinued treatment in the OLE due to elevated CSF protein.