Phase 2 Data Suggest Heterogeneity of Presentation and Comorbidity Burden Do Not Impact Activity of SAGE-547 in Patients with Super-Refractory Status Epilepticus (P4.210)

Objective: To demonstrate SAGE-547 activity despite the heterogeneity of causes of super-refractory status epilepticus (SRSE) and high comorbidity burden. Background: 547-SSE-201 was an open-label, phase 1/2 study designed to evaluate safety and efficacy of SAGE-547 in patients with SRSE. Entry criteria were designed to maximize patient treatment opportunities. Design/Methods: Patients aged ≥2 years with SRSE who were on a continuous intravenous infusion of ≥1 third-line agent (propofol/midazolam/pentobarbital/ketamine) for seizure or burst suppression were eligible for the study, if breakthrough seizures occurred during a wean attempt from or during maintenance of the third-line agent. Patients with anoxic brain injury or a very short life expectancy were excluded. Results: Nine of the 25 patients were female. Average age was 48 years (range 10-76 years). The probable cause of SRSE was varied, the more common causes being infection, intracranial bleeds, worsening seizures, primary and secondary brain tumors, and toxic ingestion. In 3 cases the cause was unknown. Patients presented with at least 5 significant comorbid medical conditions, and 23 were rated at baseline to be among the most extremely ill patients in the hospital. The average duration of SE prior to enrollment was 9 days (range 3-20 days); patients required 1 to 2 third-line agents and 1-5 AEDs. Up to 8 weans from these third-line agents were attempted prior to enrollment in the study. Despite the severity of the SRSE and the burden of comorbid conditions, 17/22 evaluable patients (77[percnt]) were successfully weaned off both their third-line agent(s) and SAGE-547; 11/22 patients (50[percnt]) reported their final Glasgow Coma Score in the study as ≥13. Six patients (24[percnt]) died, all from the underlying cause of SRSE or associated comorbid conditions. Conclusion: It is feasible to prospectively study very sick patients with SRSE, and to demonstrate drug activity despite the heterogeneity of cause of SRSE. Disclosure: Dr. Colquhoun has received personal compensation for activities with Sage Therapeutics. Dr. Baird received personal compensation for activities with Sage Therapeutics. Dr. Raines has received personal compensation from 2-B-Analytics. Dr. Jonas has received personal compensation for activities with SAGE Therapeutics. Dr. Kanes has received personal compensation for activities with Sage Therapeutics.