Brexanolone as adjunctive therapy in super-refractory status epilepticus

Eric S. Rosenthal*, Jan Claassen, Mark S. Wainwright, Aatif M. Husain, Henrikas Vaitkevicius, Shane Raines, Ethan Hoffmann, Helen Colquhoun, James J. Doherty, Stephen J. Kanes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Objective: Super-refractory status epilepticus (SRSE) is a life-threatening form of status epilepticus that continues or recurs despite 24 hours or more of anesthetic treatment. We conducted a multicenter, phase 1/2 study in SRSE patients to evaluate the safety and tolerability of brexanolone (USAN; formerly SAGE-547 Injection), a proprietary, aqueous formulation of the neuroactive steroid, allopregnanolone. Secondary objectives included pharmacokinetic assessment and open-label evaluation of brexanolone response during and after anesthetic third-line agent (TLA) weaning. Methods: Patients receiving TLAs for SRSE control were eligible for open-label, 1-hour brexanolone loading infusions, followed by maintenance infusion. After 48 hours of brexanolone infusion, TLAs were weaned during brexanolone maintenance. After 4 days, the brexanolone dose was tapered. Safety and functional status were assessed over 3 weeks of follow-up. Results: Twenty-five patients received open-label study drug. No serious adverse events (SAEs) were attributable to study drug, as determined by the Safety Review Committee. Sixteen patients (64%) experienced ≥1 SAE. Six patient deaths occurred, all deemed related to underlying medical conditions. Twenty-two patients underwent ≥1 TLA wean attempt. Seventeen (77%) met the response endpoint of weaning successfully off TLAs before tapering brexanolone. Sixteen (73%) were successfully weaned off TLAs within 5 days of initiating brexanolone infusion without anesthetic agent reinstatement in the following 24 hours. Interpretation: In an open-label cohort of limited size, brexanolone demonstrated tolerability among SRSE patients of heterogeneous etiologies and was associated with a high rate of successful TLA weaning. The results suggest the possible development of brexanolone as an adjunctive therapy for SRSE requiring pharmacological coma for seizure control. Ann Neurol 2017;82:342–352.

Original languageEnglish (US)
Pages (from-to)342-352
Number of pages11
JournalAnnals of neurology
Volume82
Issue number3
DOIs
StatePublished - Sep 2017

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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