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, including nearly 7% of adults in the United States.
Although antidepressant drugs are available, millions of depression patients are poorly served by current therapies, many of which require several weeks before therapeutic benefits are achieved.
Ketamine, a classic NMDA receptor (NMDAR) channel blocker, has been shown in 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. However, the potential for widespread clinical use of ketamine has been severely limited by its high risk for abuse and behavioral impairment, and its requirement for i.v. administration in a clinical setting.
VistaGen’s AV-101 is a novel, potent, oral NMDAR glycineB-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. In two randomized, double-blind, placebo-controlled Phase I clinical studies, 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. We are preparing to initiate Phase 2 clinical development of AV-101 in Major Depressive Disorder in early-2015 to address the high unmet need for a safe, faster-acting, more effective treatment for depression.
With mature, adult human heart cells and liver cells produced using our proprietary pluripotent stem cell technology, we have developed two 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 animals or humans. 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.