VistaGen Reports Positive Preclinical Data Differentiating Mechanism of Action of PH94B from Risk-Ridden Benzodiazepines
BY PR Newswire
— 8:30 AM ET 11/12/2020
SOUTH SAN FRANCISCO, Calif., Nov. 12, 2020 /PRNewswire/ -- VistaGen Therapeutics , a biopharmaceutical company developing new generation medicines for anxiety, depression and other central nervous system (CNS) disorders, today announced new in vitro electrophysiology data demonstrating that the mechanism of action of PH94B, the intranasal neuroactive steroid the Company is preparing for Phase 3 development as a potential acute rapid-onset treatment of anxiety in adults with social anxiety disorder, does not involve direct activation of GABA-A receptors, in distinct contrast to the mechanism of action of benzodiazepines ("benzos"), which act as direct positive modulators of GABA-A receptors.
Social anxiety disorder (SAD) affects as many as 20 million Americans and is the second most commonly diagnosed anxiety disorder.
"We are very pleased with the results of these studies that suggest PH94B's mechanism of action may not have benzodiazepine-like side effects, such as sedation and cognitive impairment, or abuse liability," stated Shawn K. Singh, Chief Executive Officer of VistaGen. "While benzodiazepines provide relief for many Americans struggling with anxiety, their extremely risky safety profile does not lend itself to long term use. The mechanism of action contributes to the safety profile. As we have seen in Phase 2 clinical studies, while PH94B is able to produce rapid-onset benzo-like, anti-anxiety effects, this study demonstrates that PH94B does not have a benzo-like mechanism of action. As we approach Phase 3 development of PH94B, especially given the FDA's recent public announcement about safety concerns associated with benzo use, these new data make us even more excited about PH94B's potential to change lives without the risky side effects and safety concerns of benzos."
Recently, the U.S. Food and Drug Administration (FDA) released a Drug Safety Communication (DSC) detailing the risks associated with use of benzodiazepines, a class of drugs commonly prescribed for treatment of anxiety disorders and other conditions. According to the FDA communication, 92 million benzodiazepine prescriptions were filled in 2019. The FDA's 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.
"We thought it was important to conduct a study to help differentiate the mechanism of action of PH94B from that of benzodiazepines, therefore, we contracted with EuroFins Discovery to determine whether PH94B has positive modulatory effects on GABA receptors using in vitro patch clamp electrophysiology," noted Mark A. Smith, M.D., Ph.D., Chief Medical Officer of VistaGen. "Benzodiazepines such as alprazolam and diazepam mediate their anti-anxiety effects by acting as positive modulators at GABA receptors to make them more responsive to GABA and thereby increase inhibitory neuronal activity in the brain. PH94B had no agonist or antagonist effects on GABA receptors. While PH94B may regulate endogenous GABA circuits in the brain, it does not appear to directly bind to or modulate GABA receptors at concentrations <10mM, which differentiates its mechanism of action from benzodiazepines."
These studies are significant because they indicate that PH94B has no relevant benzodiazepine-like activity. With widespread anxiety-provoking stressors related to the COVID-19 pandemic, civil unrest, election results, the economy, and distance learning during 2020, the number of individuals facing anxiety disorders is rising and a safer treatment alternative to benzodiazepines is imperative. PH94B may have the potential to displace benzodiazepines and become the safer alternative in the drug treatment paradigm for anxiety disorders.
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