BIIB093 (IV glibenclamide): an investigational compound for the prevention and treatment of severe cerebral edema. (2nd December 2019)

• Record Type: Journal Article
• Authors: Pergakis, Melissa; Badjatia, Neeraj; Chaturvedi, Seemant; Cronin, Carolyn A.; Kimberly, W. Taylor; Sheth, Kevin N.; Simard, J. Marc
• Is Part Of: Expert opinion on investigational drugs. Volume 28:Number 12(2019)
• Page Start: 1031
• Page End: 1040
• Publication Date: 2019-12-02
• Subjects: Glibenclamide -- BIIB093 -- SUR1-TRPM4 -- large hemispheric infarction -- stroke -- traumatic brain injury -- contusion -- cerebral edema; Drugs -- Design -- Periodicals; Drugs, Investigational -- Bibliography; Drugs, Investigational -- Periodicals; 615.1
• DOI: 10.1080/13543784.2019.1681967
• Languages: English
• ISSNs: 1354-3784

Abstract

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.