Brexanolone as adjunctive therapy in super-refractory status epilepticus.

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Rosenthal, ES; Claassen, J; Wainwright, MS; Husain, AM; Vaitkevicius, H; Raines, S; Hoffmann, E; Colquhoun, H; Doherty, JJ; Kanes, SJ

Published Date

  • September 2017

Published In

Volume / Issue

  • 82 / 3

Start / End Page

  • 342 - 352

PubMed ID

  • 28779545

Pubmed Central ID

  • PMC5639357

Electronic International Standard Serial Number (EISSN)

  • 1531-8249

Digital Object Identifier (DOI)

  • 10.1002/ana.25008


  • eng

Conference Location

  • United States