First Participant Enrolled in Phase 3 Trial of Fasedienol for Social Anxiety Disorder

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Vistagen has enrolled the first participant in the PALISADE-3 phase 3 trial of fasedienol, an investigational pherine candidate for the acute treatment of social anxiety disorder (SAD).¹ The US Food and Drug Administration has already granted Fast Track designation for the investigation of fasedienol for the acute treatment of SAD back in late 2019.²

“Initiating PALISADE-3 is another major milestone in our plan to develop and commercialize fasedienol as the first treatment of its kind for social anxiety disorder,” said Shawn Singh, chief executive officer of Vistagen. “We look forward to initiating PALISADE-4 in the second half of this year and advancing our innovative pherine pipeline to deliver pioneering neuroscience to patients affected by mental health disorders and unsatisfied with current treatments.”

Fasedienol—a first-in-class, rapid-onset investigational pherine nasal spray—is different than any currently approved anxiety medication. Its novel proposed mechanism of action separates it from SSRIs and SNRIs currently approved for the treatment of SAD, and even benzodiazepines prescribed off-label, as it regulates the olfactory-amygdala neural circuits of fear and anxiety and attenuates the tone of the sympathetic autonomic nervous system, without systemic distribution, potentiation of GABA-A receptors, or direct activity on neurons in the brain.

The randomized, double-blind, placebo-controlled PALISADE-3 phase 3 study is designed to evaluate the efficacy, safety, and tolerability of the acute administration of fasedienol to relieve anxiety symptoms in participants with SAD. Approximately 236 adults aged 18-65 will be randomized in a 1:1 ratio to either fasedienol or placebo. Anxiety symptoms will be induced by a public speaking challenge conducted in the clinical setting. The primary outcome measure is the participant self-rated Subjective Units of Distress Scale (SUDS). Any participant who completes PALISADE-3 will have the option to enroll in an open-label extension.

PALISADE-3 builds upon the research of PALISADE-2, another earlier phase 3 trial which met its primary endpoint, in which fasedienol demonstrated a statistically significant difference in average SUDS score during a public speaking challenge when compared with placebo (P=0.015). Additionally, the trial also met its secondary endpoint; there was a statistically significant difference in the proportion of clinician-assessed responders between fasedienol and placebo as measured by the CGI-I scale (P=0.033). Fasedienol was well-tolerated and demonstrated a favorable safety profile consistent with all prior trials. Fasedienol has not demonstrated any signals of abuse potential or physical dependence in any clinical trial conducted to date.³

“Fasedienol demonstrated a rapid and very clinically meaningful reduction in SUDS score, indicating a single administration has the potential to reduce anxiety symptoms during an anxiety-provoking situation,” said Michael R. Liebowitz, MD, innovator of the Liebowitz Social Anxiety Scale, former Columbia University psychiatrist, director and founder of the Anxiety Disorders Clinic at the New York State Psychiatric Institute, and current managing director of The Medical Research Network LLC in New York City.³

In the second half of 2024, Vistagen plans to initiate PALISADE-4, which will be a replicate of PALISADE-3.

SAD is an underappreciated entity that is often confused with shyness and with temperamental disposition, in which there is an underlying layer of negative cognition suggesting to the beholder that they will be judged, ridiculed, or otherwise negatively perceived. If you are interested in reading a case study on this disorder, make sure to check out the Tales From the Clinic article, “Social Anxiety Disorder: An Underappreciated Entity.”

References

1. Vistagen initiates PALISADE-3 phase 3 study of fasedienol for the acute treatment of social anxiety disorder following positive results of PALISADE-2. News release. April 1, 2024. https://www.vistagen.com/news-releases/news-release-details/vistagen-initiates-palisade-3-phase-3-study-fasedienol-acute

2. U.S. FDA grants VistaGen Therapeutics Fast Track Designation for PH94B for treatment of social anxiety disorder. News release. December 10, 2019. Accessed April 1, 2024. https://www.vistagen.com/news-releases/news-release-details/us-fda-grants-vistagen-therapeutics-fast-track-designation-ph94b

3. Vistagen announces positive top-line results from phase 3 PALISADE-2 trial of Fasedienol (PH94B) nasal spray in social anxiety disorder. News release. August 7, 2023. Accessed April 1, 2024. https://www.vistagen.com/news-releases/news-release-details/vistagen-announces-positive-top-line-results-phase-3-palisade-2