RespireRx Pharmaceuticals Inc (fka RSPI)

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>>> October 12, 2007
CX717: Cortex Pharmaceutical’s Ampakine Drug for ADHD Struck Down by FDA
Analysis of: FDA's Psychiatric Division has Rejected Cortex’s Request to Study CX717 in Phase IIb ADHD Study |

www.pipelinereview.com
Analysis By:Louis Sanfilippo, MD
Assistant Clinical Professor of Psychiatry, YALE UNIVERSITY OF MEDICINE

Implications: The FDA’s decision to not approve the investigational new drug application for CX717 (Cortex Pharmaceuticals) in the treatment of ADHD is bad news for the class of molecules known as ampakines and certainly for Cortex, which has experienced a handful of setbacks over the years. Ampakines have recently been considered a promising and potentially safer treatment for neuropsychiatric disorders such as ADHD, Alzheimer’s Disease, Fragile X syndrome, and various forms of cognitive impairment.

Analysis: Ampakines potentiate neurotransmission at AMPA-type glutamate receptors, enhance arousal and attention, and have shown potential neuroprotective effects. The FDA’s denial, based on animal toxicity studies, suggests to me that there may be evidence that CX717 had some neurotoxic effects. Overexcitation of AMPA-type glutamate receptors have been shown to cause cell death.

Cortex’s CX717 has had issues before around dosing and toxicity, including a hold placed on their Alzheimer’s study which was recently lifted. Cortex previously dampened concerns about toxicity in their animal studies commenting that histopathologic changes were only post-mortem artifacts - the FDA's decision signals another view. Dosing seems to have been problematic for CX717 with possibly too narrow a range between effectiveness and toxicity. While Cortex states they will pursue an Alzheimer’s and respiratory depression platform for CX717, the picture does not look very good. Among other setbacks for Cortex was a recent controlled trial showing no benefit over placebo for enhancing memory or cognition in Fragile X patients; and a failed clinical trial for enhancing cognitive performance and alertness in night shift work sponsored by the Defense Advanced Research Projects Agency (DARPA). Since Cortex had been featured in Business Week some several years ago with promising new treatments for Alzheimer’s Disease, the trajectory has been mainly downward. Other AMPA developments: a recently published study for Eli Lilly’s LY451395, an AMPA modulator, for Azheimer’s Disease showed no benefit over placebo. GSK729327 (GlaxoSmithKline) is another AMPA modulator in development for cognitive problems associated with schizophrenia and currently in Phase I trials. <<<