New Preliminary Positive Data From Open-Label Extension of Phase 3 Study: Fasedienol for the Acute Treatment of Social Anxiety Disorder

Vistagen today announced preliminary positive data from the open-label extension (OLE) portion of its PALISADE-4 phase 3 study of fasedienol for the acute treatment of social anxiety disorder (SAD).¹

In a recent analysis of participants who elected to participate in the OLE portion of PALISADE-4 (safety population: N=322), administration of 3.2 µg of fasedienol, taken as needed up to 6 times per day in anxiety-provoking social and performance situations in everyday life for up to 12 months, was well-tolerated with no new drug-related safety findings. Exploratory efficacy data over the first 4 months of as-needed treatment demonstrated improvement over time on both the Liebowitz Social Anxiety Scale (LSAS) and the Social Phobia Inventory (SPIN).

“These preliminary PALISADE-4 OLE results are important because they reflect the potential impact of repeated, as-needed use of fasedienol in everyday life settings where social anxiety symptoms occur,” said Angel S. Angelov, MD, the chief medical officer of Vistagen. “These findings contribute to the deep clinical dataset informing our understanding of fasedienol’s potential clinical utility to help patients experience less fear, anxiety, and avoidance in social and performance situations over time.”

PALISADE-4

PALISADE-4 was a US-based, multi-center, randomized, double-blind, placebo-controlled phase 3 public speaking challenge study designed to evaluate the efficacy and safety of fasedienol in reducing anxiety symptoms during a simulated single-dose, clinic-based public speaking challenge, measured using the Subjective Units of Distress Scale (SUDS). PALISADE-4 participants who chose to continue with the OLE portion of the study could use fasedienol as needed in their daily lives up to 6 times per day for up to 12 months.

Then in June 2026, Vistagen shared topline results from the randomized portion of PALISADE-4.² The single-dose randomized portion of the study did not achieve its primary endpoint in the overall study population, as measured by the least squares mean change from baseline on the SUDS for fasedienol compared with placebo. The favorable safety results observed for fasedienol were consistent with those observed in previously completed clinical trials. In a post-hoc analysis of a subpopulation of patients with very severe social anxiety defined by a baseline score at screening of 95 or greater on the Liebowitz Social Anxiety Scale (LSAS) (n=123), fasedienol was nominally statistically significant as measured by the LS mean change from baseline on the SUDS score for fasedienol (-12.8+/-3.4 SE) compared with placebo (-3.7 +/-3.4 SE), with a difference in the LS means of -9.1 (P=0.036).

The OLE Portion

The OLE portion of PALISADE-4 was designed to evaluate the safety and tolerability of multiple, as-needed intranasal administrations of fasedienol (up to 6 times daily, maximum daily dose of 19.2 µg fasedienol) in adults with SAD over time in an everyday life setting. Monthly safety and tolerability assessments included change in adverse events, laboratory values, 12-lead electrocardiograms, physical examinations, and vital sign assessments. Investigators evaluated change from baseline over time in standard clinical measurements, including the LSAS and SPIN, as participants used fasedienol in anxiety-provoking social and performance situations in their everyday lives.

Endpoints of the OLE portion included monthly evaluation of change from baseline at study entry on the LSAS and Month 1 and Month 4 evaluation of change from baseline at study entry on the SPIN patient self-report questionnaire. Both scales provide validated psychological assessments of the severity of SAD, with a focus on fear, avoidance, and physiological discomfort in social and performance situations.

As previously noted, investigators used the LSAS, a clinician-administered scale (range 0-144) which assesses both fear or anxiety and avoidance across 24 standardized anxiety-provoking social-interaction and performance situations, with the goal of capturing not only how distressing situations are, but also whether participants entered, tolerated, remained in, or avoided them. Preliminary analysis of the data cut (July 24, 2026) from the initial 4-month period in the OLE portion of PALISADE-4 demonstrated a clinically relevant improvement from repeated as-needed use of fasedienol over time on the LSAS for subjects participating in the OLE.

At study entry, the mean baseline LSAS score (99.3, n=320) indicated very severe social anxiety (≥95). By month 1, mean improvement on the LSAS was 20.2 points (n=298, 44% had a ≥ 20 point-improvement). By month 2, mean improvement on the LSAS was 24.6 points (n=273, 54% had a ≥ 20 point-improvement). By month 3, mean improvement on the LSAS was 29.1 points (n=240, 60% had a ≥ 20 point-improvement). Finally, by month 4, mean improvement on the LSAS was 31.4 points (n=197, 65% had ≥ 20 point-improvement).

Continued improvements were observed through each month on both the fear or anxiety and avoidance subscales of the LSAS, suggesting that participants engaging in everyday life experienced less fear or anxiety and avoidance of anxiety-provoking situations. The mean change in LSAS achieved by month 2 showed a clinically meaningful improvement of 2 social anxiety disorder severity categories, which was maintained through month 4. The percentage of participants who improved by 2 social anxiety disorder severity categories also increased steadily over 4 months. Social anxiety disorder severity categories based on the LSAS are defined as: 0-29 minimal (remission, patient does not suffer social anxiety disorder); 30-49 (mild); 50-64 (moderate); 65-79 (marked); 80-94 (severe); ≥95 (very severe).

Investigators also utilized the SPIN, a 17-item patient-reported scale (range 0-64) which measures fear, avoidance, and physiological components of social phobia over time. The recent preliminary analysis of the initial 4-month data cut from the OLE portion demonstrated consistent improvement over time on the SPIN for subjects participating in the OLE.

At study entry, the mean baseline SPIN score (48.5, n=321) indicated severe social anxiety (≥41). By month 1, mean improvement on the SPIN was 10.5 points (n=299, 45% had a ≥ 10-point improvement). By month 4, mean improvement on the SPIN was 14.9 points (n=199, 59% had a ≥ 10-point improvement).

Next Steps

Vistagen believes that results from a placebo-controlled phase 2 crossover study of fasedienol and the open-label extensions of the PALISADE phase 3 studies conducted to date in everyday life settings suggest that acute treatment with fasedienol, administered as-needed at the patient’s discretion, was accompanied by a persistent change in the overall severity of SAD, including observed reductions in fear, anxiety, and avoidance as measured by the LSAS over the course of fasedienol usage. Vistagen is now preparing to meet with the FDA to consider a proposed new registrational phase 3 clinical trial of fasedienol in SAD.

References

1. 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. News release. September 22, 2026. Accessed September 22, 2026. https://www.vistagen.com/news-releases/news-release-details/vistagen-announces-preliminary-positive-data-open-label

2. Vistagen announces topline and post-hoc data from PALISADE-4 phase 3 public speaking challenge trial of fasedienol for the acute treatment of social anxiety disorder. News release. June 30, 2026. Accessed September 22, 2026. https://www.vistagen.com/news-releases/news-release-details/vistagen-announces-topline-and-post-hoc-data-palisade-4-phase-3