NXY-059

Abstract

Marc Fisher MD Kennedy Lees MD Section Editors The SAINT I trial published in the February 9, 2006 issue of the New England Journal of Medicine represents the first “positive” neuroprotective trial in stroke.1 This breaks a long string of “neuroprotective” failures and indicates some hope for stroke treatment.2 Is NXY-059 a better drug than previous failed agents or was the trial just better designed? Probably both. NXY-059 is the first agent that fulfilled all the Stroke Therapy Academic Industry Roundtable (STAIR) recommendations regarding preclinical development before it entered a large phase-III clinical trial in stroke.3 The preclinical data with NXY-059 were robust and impressive. NXY-059 was effective at both reducing infarct size and improving functional outcome in both temporary and permanent rodent middle cerebral artery (MCA) occlusion models.4,5 There was a clear dose response and the therapeutic window extended out to 4 hours.5 Next, NXY-059 was tested in a nonhuman primate model, albeit the lissencephalic marmoset.6,7 Again, NXY-059 both reduced infarct size and improved long-term (10-week) functional outcome (reduced neglect and improved arm function) with a 4-hour window in a permanent MCA occlusion model.7 The reduction in infarct size and functional improvement was better than that observed with other neuroprotective agents (the GABA mimetic agent, clomethiazole and the NMDA antagonist, AR-R15896AR) …