Stoke Therapeutics has announced new data from its Phase 1/2a and open-label extension (OLE) studies on zorevunersen, a potential disease-modifying treatment for Dravet syndrome. The data revealed significant and lasting reductions in convulsive seizure frequency in patients who received zorevunersen alongside existing anti-seizure medications. Furthermore, the study showed continuous improvements in cognition and behavior measures over a two-year period in the OLE group. Zorevunersen was well tolerated throughout the studies, strengthening its potential as a transformative treatment for Dravet syndrome.
Dravet syndrome is a severe form of epilepsy that often does not respond well to conventional anti-seizure medications. Despite the use of the best available anti-seizure drugs, patients with Dravet syndrome still experience frequent and debilitating seizures, along with developmental delays and behavioral challenges. These new data suggest that zorevunersen may offer meaningful benefits in these areas, providing hope for patients and families.
Joseph Sullivan, M.D., FAES, Professor of Neurology and Pediatrics at the University of California, San Francisco, expressed optimism about the findings. He highlighted the unprecedented improvements observed in the study, particularly in seizure frequency and neurodevelopment, and emphasized the potential for zorevunersen to usher in a new era in Dravet syndrome treatment.
Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics, also praised the long-term data, which provide a more comprehensive view of zorevunersen’s potential. He noted that patients in the study, who had high seizure rates despite current treatments, experienced substantial and durable seizure reductions, especially those who received higher initial doses of 70mg. These results, combined with improvements in cognition and behavior, support Stoke’s plans for a Phase 3 registrational study.
Key Study Findings
Seizure Reduction:
Previously reported data from the Phase 1/2a study showed an 85% reduction in convulsive seizures at three months and a 74% reduction at six months in patients who received 70mg of zorevunersen. Data from the OLE study indicated that patients continued to experience significant reductions in seizure frequency. After at least two doses of 45mg, patients saw a median reduction of 50% from baseline at each month of the OLE, with an impressive 87% median reduction by month eight.
Cognition and Behavior Improvement:
Patients treated with zorevunersen also demonstrated continuous improvements in cognitive and behavioral function. These gains were measured using the Vineland-3 assessment, and further improvements were noted within the first nine months in patients from the Phase 1/2a ADMIRAL study.
Safety Profile
Zorevunersen was generally well tolerated in both the Phase 1/2a and OLE studies. Of the 81 patients treated in the Phase 1/2a trials, 30% experienced treatment-emergent adverse events (TEAEs) related to the study drug, most commonly including CSF protein elevations and procedural vomiting. Additionally, 22% experienced serious adverse events, which were largely unrelated to the treatment, with one previously reported case of Suspected Unexpected Serious Adverse Reactions (SUSARs). In the OLE studies, 79% of patients showed elevated CSF protein levels, although no clinical manifestations were observed.
To date, 82% of patients who enrolled in the OLE studies have continued treatment. Only one patient discontinued due to elevated CSF protein levels, underscoring the manageable safety profile of zorevunersen.
These findings highlight the promising potential of zorevunersen as a disease-modifying treatment for Dravet syndrome. The company is preparing for a Phase 3 study to further explore its efficacy and safety, and discussions with global regulatory agencies are underway.
