Vistagen Completes Phase 3 PALISADE-3 Trial Evaluating Fasedienol for Acute Treatment of Social Anxiety Disorder
Vistagen (Nasdaq: VTGN), a late clinical-stage biopharmaceutical company advancing neuroscience through innovative nose-to-brain therapeutics, announced the completion of patient participation in the randomized, double-blind, placebo-controlled portion of its PALISADE-3 Phase 3 clinical trial evaluating fasedienol for the acute treatment of social anxiety disorder (SAD). The company confirmed that the last patient has finished the core treatment phase, marking a significant step forward in Vistagen’s mission to bring a novel, fast-acting therapy to millions living with this challenging mental health condition. The study’s open-label extension remains ongoing, allowing continued evaluation of fasedienol’s use in real-world settings.
A Major Clinical Milestone for Vistagen
Commenting on this milestone, Shawn Singh, President and Chief Executive Officer of Vistagen, emphasized the company’s growing momentum in its late-stage development program.
The completion of the PALISADE-3 Phase 3 public speaking challenge study marks an important milestone for Vistagen,” said Singh. “As we advance toward our expected topline results later this quarter, we remain encouraged by fasedienol’s potential to become the first and only acute treatment for the more than 30 million people living with social anxiety disorder. We are grateful to all the individuals who participated in this study, as well as the clinical investigators, site staff, and our contract research organization for their commitment and collaboration.”
Singh’s remarks underscore the high unmet medical need that persists in social anxiety disorder, where current treatment options are limited mainly to chronic antidepressant therapy and benzodiazepines—both associated with side effects, delayed onset of efficacy, or potential for dependence. In contrast, fasedienol, an intranasal formulation designed to act rapidly on neural circuits associated with fear and anxiety, could transform the way acute symptoms of social anxiety are managed.
Building on Previous Positive Data
The completion of PALISADE-3 follows the company’s strong Phase 3 results from the PALISADE-2 trial, which were reported in August 2023. That study demonstrated statistically significant and clinically meaningful improvement in anxiety symptoms following a single dose of fasedienol compared with placebo during a simulated public speaking challenge, a validated experimental model for assessing acute anxiety in individuals with SAD.
Encouraged by these results, Vistagen initiated PALISADE-3 and PALISADE-4, both of which are ongoing Phase 3 studies designed to confirm fasedienol’s efficacy and safety. Importantly, both trials employ the same study design and primary efficacy endpoint as PALISADE-2—the Subjective Units of Distress Scale (SUDS)—while incorporating certain protocol and operational enhancements such as improved site training, more rigorous subject screening, and enhanced data surveillance to ensure consistency and reliability of outcomes.
Vistagen expects to report topline results from PALISADE-3 later in 2025, while the topline data from PALISADE-4 are anticipated during the first half of 2026. Together, these trials are expected to generate a comprehensive dataset that could support a future New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) for fasedienol as an acute, on-demand treatment for SAD.
Understanding the PALISADE Program
The PALISADE clinical program is designed around the concept of the public speaking challenge (PSC), a well-established, reproducible method for inducing social stress and measuring physiological and emotional anxiety responses. Participants are asked to perform a simulated public speaking task in front of an audience while researchers measure distress using the SUDS, a subjective rating from 0 (no distress) to 100 (maximum distress).
In both PALISADE-3 and PALISADE-4, participants receive a single intranasal dose of fasedienol or placebo before the challenge, allowing researchers to assess the medication’s acute impact on anxiety symptoms. The trial’s open-label extension phase, now ongoing, enables participants who completed the double-blind portion to continue using fasedienol in their daily lives for up to 12 months, offering valuable insights into the therapy’s longer-term safety, tolerability, and effectiveness in real-world situations.
Fast Track Designation and Regulatory Outlook
The FDA has granted Fast Track designation for fasedienol’s development in the acute treatment of social anxiety disorder—a recognition that underscores the significant unmet need and potential clinical importance of the therapy. Fast Track status is intended to facilitate the development and expedite the review of drugs that demonstrate the potential to address serious conditions and fill unmet medical needs.
With the Fast Track pathway in place, Vistagen anticipates a more streamlined regulatory process, including opportunities for frequent FDA interactions, rolling review of NDA sections, and potential eligibility for priority review.
According to the company, if either PALISADE-3 or PALISADE-4 replicates the positive efficacy and safety findings observed in PALISADE-2, the combined data could provide substantial evidence of effectiveness required to support an NDA submission. Such an achievement would represent a significant step toward making fasedienol the first FDA-approved on-demand therapy specifically indicated for acute episodes of social anxiety.
The Science Behind Fasedienol
Fasedienol belongs to a novel class of compounds known as pherines, which are proprietary neuroactive molecules designed to engage receptors in the nasal chemosensory pathways that communicate directly with the brain’s limbic system—the network responsible for emotion regulation, fear, and anxiety responses.
Unlike traditional antidepressants or anxiolytics that act through systemic absorption and require weeks to months for therapeutic effect, fasedienol is engineered for rapid onset through direct nose-to-brain action, without systemic exposure or sedation. This mechanism could enable patients to manage acute anxiety episodes—such as during social interactions, presentations, or public speaking events—within minutes of administration, offering a new paradigm in psychiatric treatment.
Preclinical and clinical research has shown that pherines can modulate key neural circuits related to fear and anxiety by influencing GABAergic and glutamatergic signaling pathways without altering serotonin or dopamine levels, thereby minimizing the risk of side effects commonly seen with SSRIs or benzodiazepines.
Addressing a Significant Unmet Need
Social anxiety disorder affects more than 30 million adults in the United States alone, making it one of the most prevalent anxiety disorders. Individuals with SAD often experience intense fear of being judged, embarrassed, or scrutinized in social or performance situations. The condition can severely impair quality of life, academic and occupational performance, and interpersonal relationships.
Current pharmacological options are primarily chronic treatments such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). While effective for some patients, these drugs require daily use and can take several weeks to achieve meaningful benefit. Moreover, they may cause side effects such as weight gain, sexual dysfunction, and fatigue, leading many individuals to discontinue treatment prematurely.
Short-acting medications like benzodiazepines can reduce anxiety rapidly but carry a high risk of dependence and cognitive impairment, limiting their long-term use. In this therapeutic landscape, fasedienol’s potential as a safe, fast-acting, and non-addictive treatment could address a major gap in current psychiatric care.
Next Steps and Future Outlook
With the PALISADE-3 trial now fully enrolled and completed, Vistagen’s focus turns to analyzing the data and preparing for the release of topline results later this quarter. The company remains optimistic that these results, together with the ongoing PALISADE-4 trial and the previously successful PALISADE-2 data, will support regulatory submission and eventual commercialization.
Should the results continue to demonstrate significant efficacy and safety, Vistagen could be poised to transform the treatment landscape for social anxiety disorder, providing clinicians and patients with the first-ever on-demand pharmacotherapy tailored for acute symptom management.
In parallel, the company is expected to continue exploring additional indications for its pherine-based therapies across other psychiatric and neurological conditions characterized by dysregulated fear and anxiety responses, such as generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD).
About Social Anxiety Disorder
Social anxiety disorder is a highly prevalent, serious, and sometimes life-threatening psychiatric mental health disorder affecting over 30 million adults in the U.S. With onset typically early in life, usually during adolescence, social anxiety disorder persists for many years thereafter, with a reported mean duration of about 20 years. While often a long-term disorder, social anxiety disorder can manifest acutely when triggered by anxiety-provoking social and performance situations during which individuals with social anxiety disorder experience extreme anxiety, distress, fear, and impairment due to their feelings of embarrassment, judgment, humiliation, negative evaluation, and scrutiny.
The disorder can significantly disrupt family and social life, diminish self-esteem, and hinder occupational functioning. Anxiety associated with social anxiety disorder often results in avoidance of everyday interactions and opportunities in academic, social, and vocational settings and an increased risk of serious co-morbid depression and substance use disorders, and potentially life-threatening, suicidal ideation, and suicide.
About Vistagen
Headquartered in South San Francisco, CA, Vistagen (Nasdaq: VTGN) is a late clinical-stage biopharmaceutical company leveraging a deep understanding of nose-to-brain neurocircuitry to develop and commercialize a new class of intranasal product candidates called pherines. Pherines specifically and selectively bind as agonists on peripheral receptors on human nasal chemosensory neurons and are designed to rapidly trigger olfactory bulb-to-brain neurocircuits believed to regulate brain areas involved in behavior and autonomic nervous system activity. They are designed to achieve therapeutic benefits without requiring absorption into the blood or uptake into the brain, giving them the potential to be a safer alternative to other pharmacological options if successfully developed and approved.
Vistagen is passionate about developing transformative treatment options to improve the lives of individuals underserved by the current standard of care for multiple highly prevalent indications, including social anxiety disorder, major depressive disorder, vasomotor symptoms (hot flashes) associated with menopause and premenstrual dysphoric disorder.
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