PH94B Nasal Spray for Acute Treatment of Anxiety in Adults with Social Anxiety Disorder
Social Anxiety Disorder
Social anxiety disorder (SAD) affects as many as 23.7 million Americans and is the second most commonly diagnosed anxiety disorder.1,2 A person with SAD feels intense, persistent symptoms of anxiety or fear in certain social situations, such as meeting new people, dating, being on a job interview, answering a question in class, or talking to a cashier in a store. Doing common, everyday things in front of people causes profound anxiety or fear of being humiliated, evaluated, judged, or rejected. SAD can get in the way of going to work, attending school, or doing a wide variety of activities that occur in a situation that has the potential for interpersonal interaction. It can lead to avoidance and opportunity cost that can significantly impact a person's employment and social activities and be very disruptive to overall quality of 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 U.S. Food and Drug Administration (FDA)-approved medication for acute (as-needed) treatment of anxiety in individuals with SAD. SAD is commonly treated chronically with certain FDA-approved antidepressants, which have a slow onset of effect (several weeks) and limited therapeutic benefits, and benzodiazepines, which are not FDA-approved for treatment of SAD but are prescribed for off-label use. Both antidepressants and benzodiazepines have known side effects and safety concerns that may make them unattractive to individuals affected by SAD. Individuals affected by SAD need novel treatment alternatives with fast onset therapeutic benefits and far fewer side effects.
PH94B Nasal Spray
VistaGen’s PH94B 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 favorable safety and tolerability profile shown in all 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 a laboratory-based public speaking challenge and a social interaction challenge, PH94B, administered as a nasal spray at a non-systemic microgram dose, significantly improved the primary efficacy endpoint, as assessed using subject-reported Subjective Units of Distress Scale (SUDS), within 10 to 15 minutes of self-administration. PH94B was not observed to be addictive, sedative or have any troubling adverse events. Furthermore, in a 22-patient, four-week, randomized, double blind, placebo-controlled Phase 2 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 self-administered by subjects 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 acute treatment of SAD. VistaGen is currently conducting PALISADE-1, a U.S. multi-center, randomized, double-blind, placebo-controlled Phase 3 clinical study to evaluate the efficacy and safety of PH94B for the acute treatment of anxiety in adults with SAD. Topline results from PALISADE-1 are anticipated in mid-2022.
PH94B's Mechanism of Action
Recent in vitro electrophysiology data demonstrates 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"), a class of drugs commonly prescribed for treatment of SAD and other anxiety disorders and other conditions, which act as direct positive modulators of GABA-A receptors. These studies are significant because they indicate that PH94B has no relevant benzo-like activity.
Recently, the FDA released a Drug Safety Communication (DSC) detailing the risks associated with use of benzodiazepines. 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 potential mechanism of action demonstrating 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.