VistaGen
Therapeutics, a clinical-stage biopharmaceutical company focused on developing
innovative medicine for depression and conditions associated with the central
nervous system, has entered into a Cooperative Research and Development
Agreement (CRADA) with the U.S. National Institute of Mental Health (NIMH), a
component of the U.S. National Institutes of Health (NIH). The CRADA enables
VistaGen and the NIMH to partner on an NIH-sponsored Phase 2 clinical study of
AV-101 in subjects with Major Depressive Disorder (MDD). MDD is a pervasive and
debilitating mental disorder which affects millions of people worldwide. It has
been noted that as many as 7% of all adults have some form of MDD.
Dr.
Carlos Zarate, Chief of the Section on the Neurobiology and Treatment of Mood
Disorders and Chief of the Experimental Therapeutics and Pathophysiology Branch
at the NIMH, will be the Principal Investigator of the NIH-funded study, which
will be a randomized, double-blind, placebo-controlled, crossover Phase 2
clinical trial designed to study the efficacy and safety of an oral dose of
AV-101 taken once per day for two weeks. The study involves approximately 25
subjects with MDD. The main efficacy measure will be the Hamilton Depression
Rating Scale (HDRS) – the subject standard for measuring the severity of MDD.
The study is anticipated to be completed this year.
Mr.
H. Ralph Snodgrass, VistaGen’s President and CSO, commented, “We are excited by
the strong preclinical efficacy data supporting the ketamine-like
antidepressant effects of AV-101, as well as the rapid and efficient
oral-delivery and clinical safety range demonstrated by our successful Phase 1
clinical studies. Dr. Zarate and his team have deep experience with ketamine
and other NMDA receptor antagonists. We look forward to collaborating closely
with them to complete this important AV-101 Phase 2 study in MDD by year end.”
While
the majority of people will experience moods of depression at some point during
their lives, it should not be confused with clinically diagnosed MDD. MDD is
the chronic, pervasive feeling of unhappiness and suffering, impairing how one
functions. Symptoms of MDD include lower levels of pleasure in activities,
insomnia or hypersomnia, weight changes, fatigue, feelings of worthlessness and
guilt, poor concentration, suicidal thoughts and psychomotor agitation. It has
been estimated that suicide is the cause of death in as much as 15% of
individuals with MDD.
Current
medications available in the multi-billion dollar global antidepressant market
are known to have limited effectiveness. Because of this, their mechanism of
action, SSRIs and SNRIs, must be taken for several weeks before patients
experience any significant therapeutic benefit. Studies show that over 60% of
depression sufferers do not benefit from first round treatments, and the
likelihood of achieving remission of depressive symptoms declines with each
successive treatment attempt.
In
the placebo-controlled, double-blind clinical trials conducted by Dr. Zarate
and others at the NIMH, ketamine produced expedient antidepressant effects in
MDD patients who had not responded to approved antidepressants. Although the
potential for widespread therapeutic use of ketamine is limited by its
potential for abuse, dissociative and psychosis-like side effects, and
practical challenges associated with its required intravenous administration in
a medical center, the discovery of ketamine’s rapid onset antidepressant
effects revolutionized thinking about the MDD treatment paradigm and mechanism
of action of antidepressant medicines. The discovery also increased interest in
the development of a new generation of antidepressants with a mechanism of
action similar to ketamine’s, including a more rapid therapeutic benefit compared
to existing agents.
AV-101’s
fundamentally novel mechanism of action places it among a new generation of
glutamatergic antidepressants with potential to address millions of MDD
sufferers worldwide who are poorly served by SSRIs, SNRIs and other current
depression therapies. Similar to ketamine, AV-101 down-regulates NMDA receptor
channel activity. However, unlike ketamine’s antagonistic activity, which
results from its blocking the NMDA receptor channel, AV-101’s antagonistic
activity results from its selective binding to, and blocking of, the
functionally-required glycine-binding co-agonist site of the NMDA receptor.
Targeting the glycine-binding co-agonist site of the NMDA receptor may bypass
potential adverse effects that occur with ketamine without affecting the robust
efficacy observed in previous clinical studies. This may then result in the
“glutamate surge” that has been associated with the rapid-acting antidepressant
effects of ketamine.
To
date, NIH has awarded VistaGen $8.8 million to advance its preclinical and
Phase 1 clinical development of AV-101. In two randomized, double-blind,
placebo-controlled Phase 1 safety studies, AV-101 was well tolerated and not
associated with any severe adverse events. There were no signs of sedation,
hallucinations or schizophrenia-like side effects often associated with
ketamine and traditional NMDA receptor channel blockers.
VistaGen
is a clinical-stage biopharmaceutical company developing innovative medicine
for depression and conditions involving the central nervous system. VistaGen’s
AV-101 is a new generation orally-available NMDA receptor glycine B-site
antagonist now moving into Phase 2 clinical development for MDD. Preclinical
studies to date have shown that AV-101 may also have potential as a treatment
for other CNS-related conditions, including chronic neuropathic pain and
epilepsy, Parkinson’s and Huntington’s disease. VistaGen is using its
proprietary pluripotent stem cell technology and clinically-predictive bioassay
systems, CardioSafe 3D™ and LiverSafe 3D™, for drug rescue applications focused
on producing proprietary, novel new chemical entities (NCEs) that are safer
versions of drug candidates previously optimized and tested for efficacy by
pharmaceutical companies.
For
more information on the company, visit www.vistagen.com
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