BIIB093 (IV glibenclamide): an investigational compound for the prevention and treatment of severe cerebral edema
Year: 2019
Type: article
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.
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1044130170, Metabolomic predictors of stroke in REGARDS, G2145263961, G3194262000, G4479290998, G46503767, Astrocyte regulation of the blood-brain barrier in intracerebral hemorrhage, G6230834768, The Recovery in Stroke Using PAP (RISE UP) Study, G7833360837, Yale Clinical Site: Investigations For Improved Neurological Treatments at Yale (INFINITY), Intensive Blood Pressure Reduction in Deep Intracerebral Hemorrhage, G878158308, Yale Clinical and Translational Science Award
OpenAlex ID: W2980602255