VistaGen’s PH10 Nasal Spray Demonstrates Different Mechanism of Action from Benzodiazepines in Preclinical Study
March 11 2021 - 7:30AM
VistaGen Therapeutics, Inc. (NASDAQ: VTGN), a biopharmaceutical
company committed to developing and commercializing a new
generation of medicines with the potential to go beyond the current
standard of care for anxiety, depression and other central nervous
system (CNS) disorders, today announced preclinical data
demonstrating that the potential mechanism of action of PH10, its
Phase 2 investigational pherine nasal spray with potential as a
rapid-onset, stand-alone treatment for major depressive disorder
(MDD), does not involve direct activation of GABA-A
receptors, in distinct contrast to the mechanism of action of
benzodiazepines, which act as direct positive modulators of GABA-A
receptors. Instead, PH10 is designed to engage receptors in nasal
chemosensory neurons which in turn regulate neurons in the limbic
amygdala that release excitatory neurotransmitters producing
rapid-onset antidepressant effects.
"These preclinical data suggest that PH10's
mechanism of action does not work through GABA-A receptors, unlike
many other neurosteroids, suggesting it may not have
benzodiazepine-like side effects, such as sedation and cognitive
impairment, or abuse liability," stated Mark Smith, MD, PhD, Chief
Medical Officer of VistaGen. “Using in vitro patch clamp
electrophysiology, PH10 had no agonist or antagonist effects on
GABA receptors. While PH10 may regulate endogenous GABA circuits in
the brain, it does not appear to directly bind to or modulate GABA
receptors at concentrations of less than 10 micromolar, which
differentiates its mechanism of action from that of
benzodiazepines.”
In September 2020, the U.S. Food and Drug
Administration (FDA) released a Drug Safety Communication (DSC)
detailing the risks associated with use of benzodiazepines.
According to the FDA’s communication, 92 million benzodiazepine
prescriptions were filled in 2019. The DSC detailed safety concerns
regarding the serious risks of abuse, addiction, physical
dependence, and withdrawal reactions linked to long-term use of
benzodiazepines, and the FDA announced that it is requiring an
updated Boxed Warning, the FDA’s most prominent type of safety
warning, for all benzodiazepine medications.
According to the World Health Organization, MDD
affects more than 264 million adults globally. In the U.S., MDD is
one of the most common mental health disorders, with over 17
million adults having experienced at least one major depressive
episode within the most recent year (2017) reported by the U.S.
National Institute of Mental Health. For some individuals, MDD can
result in severe impairments that interfere with or limit one’s
ability to carry out major life activities and can have significant
emotional, functional, and economic impact on those who suffer from
the disorder as well as their loved ones.
The current most commonly prescribed oral
antidepressants are selective serotonin reuptake inhibitors (SSRIs)
and serotonin-norepinephrine reuptake inhibitors (SNRIs). SSRIs are
intended to increase the amount of available serotonin by
inhibiting the reuptake of serotonin in the brain, preventing nerve
cells from reabsorbing serotonin and reducing the levels in the
brain. SNRIs similarly are intended to inhibit the reuptake of
serotonin and another neurotransmitter, norepinephrine, and
increase the available amounts of each in the brain. While these
medications can certainly be effective in the right context, they
are associated with slow onset of action, numerous side effects and
limited therapeutic benefits, often challenging for medical
professionals to identify the right drug or combination of drugs
for particular individuals.
Recent studies have shown that there has been an
exacerbation of existing depression symptoms, with U.S. adults
showing three times as many symptoms of depression during the
COVID-19 pandemic, creating a critical need for new and
differentiated alternatives for treatment of MDD. PH10 may have the
potential to displace existing SSRIs and SNRIs as a stand-alone
alternative in the drug treatment paradigm for depression
disorders.
PH10 is a new generation antidepressant with a
mechanism of action that is designed to be fundamentally different
from all current FDA-approved antidepressants. After intranasal
administration, a non-systemic microgram-level dose of PH10 binds
to nasal chemosensory receptors that, in turn, activate key neural
circuits in the brain that can lead to rapid-onset antidepressant
effects, but without the psychological side effects or safety
concerns that may be caused by rapid-onset ketamine-based therapy,
including both intravenous ketamine and esketamine nasal spray, or
the side effects and safety concerns of current oral
antidepressants that may take many weeks to become effective.
About PH10 PH10 is a Phase 2
investigational pherine nasal spray designed to have rapid-onset
effects and therapeutic potential in several neuropsychiatric
indications involving depression. Self-administered in
microgram-level doses, PH10 does not require systemic uptake and
distribution to produce rapid-onset antidepressant effects.
Following completion of a successful exploratory Phase 2A clinical
study, VistaGen is preparing for a planned PH10 for a Phase 2B
clinical study in the U.S. as a stand-alone treatment of MDD. With
its rapid-onset pharmacology, lack of systemic exposure at clinical
doses administered to-date and favorable safety results observed in
all clinical studies to date, VistaGen believes PH10 has potential
to be a new stand-alone treatment for several depression
disorders.
About VistaGen VistaGen
Therapeutics is a biopharmaceutical company committed to developing
and commercializing innovative medicines with the potential to go
beyond the current standard of care for anxiety, depression, and
other CNS disorders. Each of VistaGen’s three drug candidates has a
differentiated potential mechanism of action, has been
well-tolerated in all clinical studies to date and has therapeutic
potential in multiple CNS markets. For more information, please
visit www.vistagen.com and connect with VistaGen on Twitter,
LinkedIn, and Facebook.
Forward Looking Statements
Various statements in this release are "forward-looking statements"
concerning our future expectations, plans and prospects, including
the potential for successful clinical development and
commercialization of PH10 for depression disorders, including MDD.
These forward-looking statements are neither promises nor
guarantees of future performance, and are subject to a variety of
risks and uncertainties which could cause actual results to differ
materially from those contemplated in these forward-looking
statements, including the risks that: development and approval of
PH10 may not be achieved in any market; the FDA or counterpart
foreign regulatory authorities may decide that the results of the
our PH10 clinical program are not sufficient for regulatory
approval for treatment of MDD or any other depression-related
disorder; development of PH10 may not be successful in any
indication; success in nonclinical studies or in earlier-stage
clinical trials may not be repeated or observed in future studies,
which may not support further development or be sufficient to gain
regulatory approval to market PH10; adverse events may be
encountered at any stage of development that negatively impact
further development. Other risks and uncertainties include, but are
not limited to, issues related to: adverse healthcare reforms and
changes of laws and regulations; general industry and market
conditions; manufacturing and marketing risks, including risks
related to the COVID-19 pandemic, which may include, but are not
limited to, unavailability of or delays in delivery of raw
materials for manufacture of PH10; inadequate and/or untimely
supply of PH10 to meet demand; entry of competitive products; and
other technical and unexpected hurdles in the development,
manufacture and commercialization of PH10, as well as those risks
more fully discussed in the section entitled "Risk Factors" in our
most recent Annual Report on Form 10-K for the year ended March 31,
2020, and in our most recent Quarterly Report on Form 10-Q for the
quarter and nine months ended December 31, 2020, as well as
discussions of potential risks, uncertainties and other important
factors in our other filings with the Securities and Exchange
Commission. In addition, any forward-looking statements represent
our views only as of today and should not be relied upon as
representing our views as of any subsequent date. We explicitly
disclaim any obligation to update any forward-looking
statements.
VistaGen Company Contact Mark
McPartland VistaGen Therapeutics Phone: (650) 577-3606 Email:
IR@vistagen.com
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