A Potential Benzodiazepine Replacement

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VistaGen Therapeutics presented data that highlighted the proposed mechanism of action (MOA) of its phase 3 investigational drug candidate PH94B in a poster session at the Anxiety and Depression Association of America’s 2021 Virtual Annual Conference. PH94B is a nasal spray designed for the treatment social anxiety disorder (SAD) without directly activating gamma-amino butyric acid (GABA_A) receptors.

This sets Ph94B’s MOA apart from that of benzodiazepines such as alprazolam, diazepam, and lorazepam, all direct GABA_A receptor positive modulators. VistaGen hopes to offer an alternative to displace these drugs, along with other highly-addictive benzodiazepines used for treating SAD and other anxiety disorders.

“The results are in agreement with PH94B’s lack of benzodiazepine-like side effects and safety concerns reported in PH94B clinical studies—for example, lack of sedation, cognitive impairment or abuse liability potential,” Louis Monti, MD, PhD, Vice President, Translational Medicine of VistaGen said to the press. “This study demonstrated that PH94B’s mechanism of action is through neural regulation of forward inhibitory GABAergic neurons in the limbic amygdala and is differentiated from benzodiazepines’ mechanism of action, which is through a direct local potentiating effect on GABA receptors. These data are key in understanding PH94B’s overall potential effectiveness and safety for individuals suffering from SAD and many other anxiety disorders.”

PH94B, an investigational odorless pherine nasal spray, also has therapeutic potential in a wide range of additional anxiety disorders and phobias. In phase 2 clinical trials, PH94B was self-administered in microgram-level doses and produced rapid-onset anti-anxiety effects within approximately 15 minutes.

To help differentiate PH94B’s MOA from that of benzodiazepines, VistaGen studied whether PH94B had positive modulatory effects on GABA receptors. For example, one of the key results reported in the poster presentation included no significant effect on GABA potentiation at doses up to 10 micromolar when compared to the 300% potentiation induced by diazepam, a commonly benzodiazepine.

“Given the FDA’s recent Drug Safety Communication that outlined and highlighted the safety risks associated with benzodiazepine use, the implications resulting from this study are significant,” said Mark Smith, MD, PhD, Chief Medical Officer of VistaGen. “PH94B may have the potential to displace benzodiazepines altogether and become the safer alternative to help the millions of Americans suffering from anxiety with limited options for safe, effective treatment options. These existing treatments can actually hurt instead of help. We look forward to launching our Phase 3 clinical development program for PH94B next quarter and continuing to push forward in our mission to get it into the hands of those in need as soon as possible.”

Further publications on PH94B can be found here.

Reference

1. Globe Newswire staff. VistaGen’s poster presentation at the Anxiety and Depression Association of America’s 2021 Annual Conference differentiates PH94B’s mechanism of action from highly-addictive benzodiazepines. VistaGen. March 22, 2021. https://ir.vistagen.com/press-releases/detail/166