Depression is a global public health concern. The World Health Organization estimates that “depression is the leading cause of disability worldwide, and is a major contributor to the global burden of disease,” affecting 350 million people globally. According to the U.S. Centers for Disease Control and Prevention (CDC), “one in 10 Americans aged 12 and over takes antidepressant medication.”
Today, millions of depression patients are poorly served by antidepressant agents, most of which require several weeks before any therapeutic benefit is achieved.
Ketamine, a classic NMDA receptor (NMDAR) channel blocker, has been shown in revolutionary clinical trials conducted by the U.S. National Institutes of Health (NIH) and others to act rapidly to alleviate symptoms of depression in treatment-resistant patients suffering with Major Depressive Disorder (MDD). However, the potential for widespread therapeutic use of ketamine has been severely limited by its side effects, high risk for abuse and behavioral impairment, and inconvenient i.v. administration in a clinical setting.
VistaGen’s AV-101 is a novel, potent, oral NMDAR glycine-binding site antagonist. In preclinical studies, AV-101 has demonstrated the robust, rapid-onset, antidepressant-like activity of ketamine, without any signs of ketamine’s side effects. Additionally, in two randomized, double-blind, placebo-controlled Phase I clinical studies funded by the NIH, AV-101 was well-tolerated, without any serious adverse events. There were no signs of sedation, hallucinations or the schizophrenia-like side effects often associated with ketamine and other classic NMDAR channel blockers.
In February 2015, VistaGen entered a Cooperative Research and Development Agreement (CRADA) with the U.S. National Institute of Mental Health (NIMH), part of the NIH. Under this agreement, VistaGen, and the NIMH, led by Principal Investigator, Dr. Carlos Zarate, will collaborate on an NIH-sponsored Phase 2 clinical efficacy and safety study of AV-101 in subjects with Major Depressive Disorder. The study is expected to begin during the first half of 2015. For more information, please read the following press release: VistaGen and NIH Sign Agreement for NIH-Sponsored Phase 2 Study of Orally-Active AV-101 in Major Depressive Disorder.
With mature, functional human heart cells and liver cells produced using our proprietary pluripotent stem cell technology, we have developed two novel customized human cellular bioassay systems, CardioSafe 3D and LiverSafe 3D, for predicting heart toxicity and liver toxicity of new drug candidates in vitro, long before they are ever tested in animal or human studies. We use CardioSafe 3D and LiverSafe 3D to advance our internal drug rescue programs, which are focused on producing new, safer variants of drug candidates previously optimized and tested for efficacy by pharmaceutical companies but terminated before FDA approval due to heart or liver toxicity concerns. Our initial drug rescue programs are focused on novel therapies for cancer.