Fasedienol for Social Anxiety Disorder Does Not Demonstrate Significant Improvement in Phase 3 Study

Vistagen announced results from the PALISADE-3 phase 3 study of intranasal fasedienol for acute treatment of social anxiety disorder, showing no statistically significant improvement in primary endpoint measures.¹ The trial did not meet primary or secondary endpoints, and showed favorable safety data consistent with previous trials.

“We are disappointed by the unexpected results of this public speaking challenge trial, which are inconsistent with positive outcomes observed in Phase 2 and our PALISADE-2 Phase 3 study,” said Shawn Singh, JD, president and chief executive officer of Vistagen, in a press release. “We are thoroughly reviewing the results of the study, evaluating the potential impact of the results on our ongoing studies and plan to seek feedback from the [US Food and Drug Administration],” he added.

The PALISADE-3 phase 3 trial was a multicenter, randomized, double-blind, placebo-controlled study evaluating efficacy and safety of single dose fasedienol. Intranasal administration of fasedienol was intended to reduce anxiety symptoms during a simulated public speaking challenge. Participant anxiety and distress symptoms were evaluated using the Subjective Units of Distress Scale (SUDS).

PALISADE-3 included adults aged 18 to 65 with a diagnosis of social anxiety disorder as defined by the DSM-5 and confirmed by a Mini-International Neuropsychiatric Interview.² Clinician-rated Liebowitz Social Anxiety Scale score of 70 or greater and Hamilton Depression Rating Scale score of less than 16 were required. Participants also needed normal olfactory function for inclusion. Exclusion criteria included any history of bipolar disorder, schizophrenia, and psychosis, among other psychiatric disorders; moderate to severe alcohol use disorder within 1 year prior to the study and use of illicit substances or THC within 2 months prior to study; risk for suicidal behavior; nasal pathology including nasal trauma, nasal surgery, anosmia; 2 or more documented failed treatment trials for social anxiety disorder; and receiving cognitive behavioral therapy.

Fasedienol did not demonstrate a statistically significant improvement in the primary endpoint measurement of SUDS. There was also no treatment difference for secondary endpoints. As measured by the least squares mean change from baseline on the SUDS score for fasedienol (13.6 +/-1.54 standard error, SE) compared with placebo (14.0 +/-1.51 SE), least squares mean difference of 0.4 (P not significant), the trial did not meet its primary endpoint. The safety profile was consistent with previous studies, although the endpoint results were not as positive as previous studies of the drug.

Fasedienol modulates the olfactory-limbic amygdala fear and anxiety neurocircuitry. The drug selectively binds as an agonist to peripheral receptors on nasal chemosensory neurons and is intended to trigger olfactory bulb-to-brain neurocircuits thought to regulate brain regions involved in behavior and autonomic nervous system activity. With the intranasal form of this medication, the design hopes to allow for therapeutic benefits without requiring absorption into blood or uptake into the brain. The design has a distinct tolerability profile because neuromodulation can occur without binding to brain neurotransmitter receptors. Vistagen noted that this formulation may have potential for a better safety profile compared with other pharmacological options. Based on nonclinical data, fasedienol showed no positive signal of abuse potential.

Patients who participated in the PALISADE-3 study may choose to continue with the open-label extension, using fasedienol for up to 12 months. The FDA has also granted Fast Track designation for the development of fasedienol for acute treatment of social anxiety disorder.³

References

1. Vistagen announces topline results from PALISADE-3 phase 3 public speaking challenge study of fasedeniol for the acute treatment of social anxiety. Press release. December 17, 2025. Accessed December 17, 2025. https://www.vistagen.com/news-releases/news-release-details/vistagen-announces-topline-results-palisade-3-phase-3-public

2. Fasedienol nasal spray for acute treatment of anxiety in adults with social anxiety disorder (PALISADE-3). ClinicalTrials.gov. November 26, 2025. Accessed December 17, 2025. https://www.clinicaltrials.gov/study/NCT06358651

3. US FDA grants VistaGen Therapeutics Fast Track designtation for PH94B for treatment of social anxiety disorder. December 10, 2019. Accessed December 17, 2025. https://www.vistagen.com/news-releases/news-release-details/us-fda-grants-vistagen-therapeutics-fast-track-designation-ph94b