BIIB093 (IV glibenclamide): an investigational compound for the prevention and treatment of severe cerebral edema

Melissa Pergakis, Neeraj Badjatia, Seemant Chaturvedi, Carolyn A. Cronin, W. Taylor Kimberly, Kevin N. Sheth, J. Marc Simard

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Introduction: Brain swelling due to edema formation is a major cause of neurological deterioration and death in patients with large hemispheric infarction (LHI) and severe traumatic brain injury (TBI), especially contusion-TBI. Preclinical studies have shown that SUR1-TRPM4 channels play a critical role in edema formation and brain swelling in LHI and TBI. Glibenclamide, a sulfonylurea drug and potent inhibitor of SUR1-TRPM4, was reformulated for intravenous injection, known as BIIB093. Areas covered: We discuss the findings from Phase 2 clinical trials of BIIB093 in patients with LHI (GAMES-Pilot and GAMES-RP) and from a small Phase 2 clinical trial in patients with TBI. For the GAMES trials, we review data on objective biological variables, adjudicated edema-related endpoints, functional outcomes, and mortality which, despite missing the primary endpoint, supported the initiation of a Phase 3 trial in LHI (CHARM). For the TBI trial, we review data on MRI measures of edema and the initiation of a Phase 2 trial in contusion-TBI (ASTRAL). Expert opinion: Emerging clinical data show that BIIB093 has the potential to transform our management of patients with LHI, contusion-TBI and other conditions in which swelling leads to neurological deterioration and death.

Original languageEnglish (US)
Pages (from-to)1031-1040
Number of pages10
JournalExpert opinion on investigational drugs
Volume28
Issue number12
DOIs
StatePublished - Dec 2 2019
Externally publishedYes

Keywords

  • BIIB093
  • Glibenclamide
  • SUR1-TRPM4
  • cerebral edema
  • contusion
  • large hemispheric infarction
  • stroke
  • traumatic brain injury

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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