PH94B Neuroactive Nasal Spray for Acute Treatment of Anxiety in Adults with Social Anxiety Disorder
Social Anxiety Disorder
Social anxiety disorder (SAD) affects as many as 20 million Americans and is the second most commonly diagnosed anxiety disorder.1,2 A person with SAD feels symptoms of extreme anxiety or fear in certain social situations, such as meeting new people, dating, being on a job interview, answering a question in class, or making small talk to a cashier in a store or a networking event at work. Doing everyday things in front of people - such as eating or drinking in front of others or using a public restroom - also causes anxiety or fear. The person is afraid that he or she will be humiliated, judged, and rejected. SAD can significantly compromise academic, social and work life and can predispose individuals to other anxiety disorders, depression and substance use disorders.3
SAD usually starts during youth. Without treatment, social anxiety disorder can last for many years or a lifetime and prevent a person from reaching his or her full potential.
There is no FDA-approved medication for acute (as-needed) treatment of anxiety in patients with SAD. While three antidepressants (two SSRIs and one SNRI) are FDA-approved for treatment of SAD, they take many weeks to work, if they work at all, must be taken chronically, and often present troubling side effects. Individuals affected by SAD need novel treatment alternatives with fast onset therapeutic benefits and far fewer side effects.
PH94B Neuroactive Nasal Spray
VistaGen’s PH94B neuroactive nasal spray is fundamentally different from all current drug treatments for SAD. PH94B binds to nasal chemosensory receptors which activate neural circuits that lead to rapid suppression of fear and anxiety. With its novel mechanism of pharmacological action, rapid-onset of therapeutic effects and exceptional safety and tolerability profile shown in clinical trials to date, PH94B has potential to become the first FDA-approved acute treatment for SAD.
In a 91-patient published, peer-reviewed, randomized, double-blind, placebo-controlled Phase 2 clinical trial, which included both laboratory-based public speaking and social situation challenges, PH94B, administered as a nasal spray at a non-systemic microgram dose, significantly improved the primary efficacy endpoint, as assessed using subjective anxiety ratings on the Subjective Units of Distress Scale (SUDS), within 10 to 15 minutes of self-administration. PH94B was not observed to be addictive, sedative or have other adverse events. Furthermore, in a 22-patient, four-week, randomized, double blind, placebo-controlled pilot Phase 3 crossover study, subjects receiving PH94B had a significantly greater decrease in average peak SUDS scores compared to placebo within one week of treatment. There was also a significantly greater decrease in Liebowitz Social Anxiety Scale (LSAS) avoidance scores for subjects who received PH94B first, before crossing over to placebo.
In all clinical studies to date, PH94B was administered intranasally at non-systemic microgram doses. PH94B's safety profile was excellent, with no placebo-like side effects and no serious adverse events.
The FDA has granted Fast Track designation for development of PH94B as a potential fast-acting neuroactive nasal spray for acute treatment of SAD. VistaGen is currently preparing for Phase 3 clinical development of PH94B for acute treatment of SAD.
PH94B's Mechanism of Action
Recent in vitro electrophysiology data demonstrating that the mechanism of action of PH94B 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. These studies are significant because they indicate that PH94B has no relevant benzodiazepine-like activity.
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.
Below is a video highlighting PH94B’s mechanism of action (MOA) - the way we believe it works to treat SAD and, potentially, other anxiety disorders where current treatments are inadequate, resulting in high unmet need.
PH94B Mechanism of Action video in Japanese (日本語)
PH94B Mechanism of Action video in Mandarin (中文)
- Harvard Medical School, 2007. National Comorbidity Survey (NCS). (2017, August 21); Kessler, et al, US National Comorbidity Survey Replication, 2005.
- Anxiety and Depression Association of America, https://adaa.org/understanding-anxiety/social-anxiety-disorder
- American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.
- Liebowitz, MR, Salman, E, Nicolini, H, Rosenthal, N, Hanover, R, Monti. L (2014). Effect of an acute intranasal aerosol dose of PH94B on social and performance anxiety in women with social anxiety disorder. Am. J. Psychiatry 171:675-682.
- Liebowitz MR, Hanover R, Draine A, Lemming R, Careri J, Monti L (2016). Effect of as‐needed use of intranasal PH94B on social and performance anxiety in individuals with social anxiety disorder. Depress Anxiety 33: 1081-1089.