Fasedienol Shows Progressive Improvement in Social Anxiety During PALISADE-4 Extension

Vistagen reported preliminary safety and exploratory efficacy data from the open-label extension of its Phase 3 PALISADE-4 study (NCT06615557) of fasedienol nasal spray in adults with social anxiety disorder. As-needed use of 3.2 µg fasedienol, up to six times daily for anxiety-provoking social and performance situations, was well tolerated, while social anxiety scores improved progressively over four months.

Fasedienol Demonstrates Favorable Long-Term Safety

The PALISADE-4 open-label extension (OLE) included 322 adults with social anxiety disorder (SAD) who elected to continue treatment after the randomized study phase.

Participants used 3.2 µg of intranasal fasedienol as needed, up to six times daily, with a maximum daily dose of 19.2 µg, during anxiety-provoking social and performance situations in everyday life. The July 24, 2026 data cutoff provided safety information extending to 12 months.

Five participants (1.6%) discontinued because of adverse events, and none of these discontinuations were attributed to fasedienol. More than 95% of treatment-emergent adverse events were mild or moderate.

The most common events were headache (18.0%), upper respiratory tract infection (9.9%), rhinorrhea (7.1%), and oropharyngeal pain (5.3%). No serious adverse events were considered related to fasedienol.

Laboratory assessments, ECGs, physical examinations, and vital signs also revealed no new safety signals of concern.

LSAS Scores Improved Progressively Over Four Months

Exploratory efficacy analyses showed increasing improvement on the Liebowitz Social Anxiety Scale (LSAS), a clinician-administered measure covering fear or anxiety and avoidance across social and performance situations.

The baseline mean LSAS score was 99.3, placing the 320 participants with available data in the very severe SAD category.

The analysis also showed improvement in both LSAS domains, suggesting reductions in reported fear or anxiety as well as avoidance.

A 20-point reduction is commonly used as a threshold for clinically meaningful improvement in LSAS-based clinical research, although the appropriate interpretation can vary by study population and methodology. The OLE analysis therefore provides supportive evidence of meaningful change, but does not establish treatment efficacy because the extension lacked a concurrent placebo control.

Patient-Reported Anxiety Also Improved

The Social Phobia Inventory (SPIN) provided a patient-reported assessment of fear, avoidance, and physiological symptoms associated with social anxiety.

The baseline mean SPIN score was 48.5, consistent with severe social anxiety.

The 10-point threshold was used by the study to characterize a clinically meaningful degree of improvement. As with the LSAS threshold, it should not automatically be interpreted as a universal MCID across all SAD populations and trial designs.

PALISADE-4 Primary Study Did Not Meet Its Endpoint

The OLE findings must be considered alongside the results of the randomized portion of PALISADE-4.

In June 2026, Vistagen reported that the placebo-controlled Phase 3 public-speaking challenge did not meet its primary endpoint. The study evaluated least-squares mean change from baseline in the Subjective Units of Distress Scale (SUDS) after a simulated public-speaking challenge.

A subsequent post-hoc analysis of 123 participants with very severe SAD, defined by an LSAS score of at least 95 at screening, found a nominally statistically significant difference in SUDS change. The least-squares mean change was -12.8 for fasedienol versus -3.7 for placebo, producing a between-group difference of -9.1 points (p=0.036).

Because this analysis was post hoc and involved a predefined subgroup rather than the overall randomized population, it does not overturn the negative primary endpoint.

FDA Discussion Planned for Next Phase 3 Study

Fasedienol is an intranasal pherine being developed to engage nose-to-brain neurocircuitry for anxiety-related conditions. The PALISADE program evaluates as-needed administration in real-world social and performance situations, rather than continuous daily treatment.

Vistagen said it plans to meet with the FDA during the current quarter to discuss a proposed new registrational Phase 3 study in SAD.

The OLE data expand the longer-term safety dataset and show progressive improvements in clinician- and patient-reported measures during repeated as-needed use. However, the open-label design and absence of a concurrent placebo group limit causal interpretation. A new controlled Phase 3 study will be important for determining whether the observed longer-term changes translate into a reproducible treatment benefit.

Reference

Vistagen Announces Preliminary Positive Data from Open-Label Extension Portion of PALISADE-4 Phase 3 Study of Fasedienol for the Acute Treatment of Social Anxiety Disorder, Vistagen, 22 September 2026

Fasedienol Nasal Spray for the Acute Treatment of Anxiety in Adults with Social Anxiety Disorder (PALISADE-4) (PALISADE-4), ClinicalTrials.gov ID NCT06615557