Vistagen’s fasedienol (PH94B) is a first-in-class, rapid-onset investigational neuroactive pherine nasal spray in Phase 3 clinical development for acute treatment of social anxiety disorder (SAD). Designed for intranasal administration in low microgram doses, the proposed novel mechanism of action (MOA) of fasedienol is fundamentally differentiated from all current anti-anxiety medications, including all antidepressants approved by the U.S. Food and Drug Administration (FDA) for the treatment of SAD, as well as all benzodiazepines and beta blockers prescribed for SAD on an off-label basis.

When administered intranasally, fasedienol activates receptors of peripheral nasal chemosensory neurons connected to subsets of neurons in the olfactory bulbs that, in turn, connect to neurons in the limbic amygdala involved in the pathophysiology of SAD and potentially other anxiety and mood disorders. Fasedienol is pharmacologically active without requiring apparent systemic absorption and distribution of the compound to the brain to achieve its rapid-onset and short duration of anxiolytic effects.

Positive PALISADE-2 Phase 3 study of fasedienol yields statistically significant top-line results for the acute treatment of anxiety in adults with SAD

Vistagen’s PALISADE-2 trial (n=141) was a multi-center, randomized, double-blind, placebo-controlled, Phase 3 clinical study of fasedienol in adults diagnosed with SAD. The study was designed to evaluate the efficacy, safety, and tolerability of the acute (single-dose) administration of fasedienol to relieve anxiety symptoms in adult patients with SAD during a simulated anxiety-provoking public speaking challenge, as measured using the patient-reported Subjective Units of Distress Scale (SUDS).

PALISADE-2 met its primary efficacy endpoint, the difference in mean SUDS score during the public speaking challenge at baseline (Visit 2) and treatment (Visit 3) for patients who received fasedienol (n=70) versus placebo (n=71) at Visit 3. Fasedienol-treated patients demonstrated a statistically significant greater change in mean SUDS score (least-squares (LS) mean = -13.8) compared to placebo (LS mean = -8.0), for a difference between groups of -5.8 (p=0.015).

The trial also met its secondary endpoint, demonstrating a statistically significant difference in the proportion of clinician-assessed responders between fasedienol and placebo as measured by the Clinical Global Impressions Improvement (CGI-I) scale. Responders were identified as those who were rated ‘very much less anxious’ or ‘much less anxious’ with 37.7% (n=70) of fasedienol-treated patients rated as responders, as compared to 21.4% (n=71) of those treated with placebo (p=0.033).

Additionally, the trial met the important exploratory endpoint of the difference in the proportion of patient-assessed responders between fasedienol and placebo as measured by the Patient’s Global Impression of Change (PGI-C) scale. Responders were identified as those who self-rated ‘very much less anxious’ or ‘much less anxious’ with 40.6% (n=70) of fasedienol-treated patients rated as responders, as compared to 18.6% (n=71) of those treated with placebo (p=0.003).

Finally, the trial also met the exploratory endpoint of the difference in the proportion of patients in each treatment group with a 20-point improvement in patient-assessed SUDS score from baseline (Visit 2) to treatment (Visit 3). Of the fasedienol-treated patients, 35.7% (n=70) demonstrated this statistically significant and clinically meaningful improvement in SUDS score, as compared to 18.6% (n=71) in the placebo-treated group (p=0.020).

Fasedienol was observed to be well-tolerated with no severe or serious adverse events (AEs) reported. All treatment-emergent AEs reported for the overall study were mild or moderate. There were no AEs reported in the fasedienol treatment arm above 2% occurrence.

Fasedienol is an investigational neuroactive pherine nasal spray with a proposed rapid-onset, non-systemic MOA that sets it apart from all currently approved anti-anxiety medications.

Potential PALISADE-3 Phase 3 study of fasedienol for the acute treatment of anxiety in adults with SAD

Based on the positive top-line results of the PALISADE-2 Phase 3 study, Vistagen is currently planning to initiate a similar PALISADE-3 Phase 3 trial, with a potential start date during the first half of calendar 2024. Like PALISADE-2, PALISADE-3 will be designed as a U.S. multi-center, randomized, double-blind, placebo-controlled, Phase 3 clinical study to evaluate the efficacy, safety, and tolerability of the acute (single-dose) administration of fasedienol to relieve anxiety symptoms in adult patients with SAD during a simulated anxiety-provoking public speaking challenge, as measured using the patient-reported SUDS as the primary outcome measure.

For more information on partnering with Vistagen, please contact us at bd@vistagen.com.