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

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.

• Authors: Melissa Pergakis, Neeraj Badjatia, Seemant Chaturvedi, Carolyn A Cronin, W Taylor Kimberly, Kevin N Sheth, J Marc Simard
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 28 Issue 12 Pg. 1031-1040 (Dec 2019) ISSN: 1744-7658 [Electronic] England
• PMID: 31623469 (Publication Type: Journal Article, Review)

Chemical References

• Drugs, Investigational
• Neuroprotective Agents
• Glyburide

Topics

• Administration, Intravenous
• Animals
• Brain Edema (prevention & control)
• Drugs, Investigational (administration & dosage, pharmacology)
• Glyburide (administration & dosage, pharmacology)
• Humans
• Neuroprotective Agents (administration & dosage, pharmacology)
• Severity of Illness Index