Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Dec 2019
ReviewBIIB093 (IV glibenclamide): an investigational compound for the prevention and treatment of severe cerebral edema.
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. ⋯ 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.