Vistagen's Fasedienol Nasal Spray Well Tolerated Over 12 Months in PALISADE-4 Open-Label Extension, With LSAS and SPIN Gains
核心洞察
Vistagen (搜索) reported preliminary positive data from the open-label extension of its PALISADE-4 Phase 3 study of fasedienol nasal spray for acute treatment of social anxiety disorder (搜索).
In 322 adults, as-needed fasedienol 3.2 micrograms up to six times daily was well tolerated for up to 12 months, with no new drug-related safety findings.
Exploratory efficacy showed mean LSAS improvement rising from 20.2 points at Month 1 to 31.4 points at Month 4, with 65% achieving at least a 20-point gain.
Vistagen (搜索) has reported preliminary positive data from the open-label extension (OLE) portion of its PALISADE-4 Phase 3 study of fasedienol nasal spray for the acute treatment of social anxiety disorder (搜索). In the safety population of 322 adults, fasedienol 3.2 micrograms taken as needed up to six times per day in anxiety-provoking social and performance situations was well tolerated for up to 12 months, with no new drug-related safety findings, according to the company's September 22 announcement.
The OLE was a voluntary extension of the randomized, double-blind, placebo-controlled portion of PALISADE-4, open to participants who chose to continue per the study protocol. It was designed to evaluate the safety and tolerability of multiple as-needed intranasal administrations of fasedienol, with a maximum daily dose of 19.2 micrograms, in adults with social anxiety disorder (搜索) in an everyday life setting. Monthly assessments included adverse events, laboratory values, 12-lead electrocardiograms, physical examinations and vital sign assessments.
Safety Profile Through 12 Months
As of a July 24, 2026 data cut-off, the rate of discontinuation due to adverse events was 1.6% (5/322), with no discontinuations attributed to fasedienol. More than 95% of treatment-emergent adverse events (TEAEs) were mild or moderate in severity. TEAEs occurring in more than 5% of subjects were headache (18.0%; 58/322), upper respiratory tract infection (9.9%; 32/322), rhinorrhoea (7.1%; 23/322) and oropharyngeal pain (5.3%; 17/322). No serious adverse events related to fasedienol were reported, and no safety signals of concern were identified related to laboratory values, ECGs, physical examinations or vital signs.
"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, M.D., Chief Medical Officer of Vistagen (搜索). "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."
Exploratory Efficacy on LSAS and SPIN
The OLE explored change from baseline at study entry on the Liebowitz Social Anxiety Scale (LSAS), a clinician-administered scale ranging from 0 to 144 that assesses fear or anxiety and avoidance across 24 standardized anxiety-provoking social-interaction and performance situations, capturing both how distressing situations are and whether patients entered, tolerated, remained in or avoided them.
At study entry, the mean baseline LSAS score was 99.3 (n=320), indicating very severe social anxiety, defined as a score of 95 or greater. Mean improvement was 20.2 points at Month 1 (n=298; 44% had at least a 20-point improvement), 24.6 points at Month 2 (n=273; 54%), 29.1 points at Month 3 (n=240; 60%) and 31.4 points at Month 4 (n=197; 65%). Continued improvements were observed on both the fear or anxiety and avoidance subscales. The mean change in LSAS achieved by Month 2 represented a clinically meaningful improvement of two social anxiety disorder (搜索) severity categories, which was maintained through Month 4, and the percentage of participants improving by two severity categories increased steadily over the four months. LSAS severity categories are defined as 0-29 minimal (remission), 30-49 mild, 50-64 moderate, 65-79 marked, 80-94 severe and 95 or greater very severe.
On the Social Phobia Inventory (SPIN), a 17-item patient-reported scale ranging from 0 to 64 that measures fear, avoidance and physiological components of social phobia, the mean baseline score was 48.5 (n=321), indicating severe social anxiety, defined as 41 or greater. Mean improvement was 10.5 points at Month 1 (n=299; 45% had at least a 10-point improvement) and 14.9 points at Month 4 (n=199; 59%).
Vistagen (搜索) said it believes 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 social anxiety disorder (搜索), including observed reductions in fear, anxiety and avoidance as measured by the LSAS over the course of fasedienol usage.
Regulatory Path After a Missed Primary Endpoint
The randomized portion of PALISADE-4, a U.S. multi-center, double-blind, placebo-controlled Phase 3 public speaking challenge study, evaluated fasedienol in reducing anxiety symptoms during a simulated single-dose, clinic-based public speaking challenge using the Subjective Units of Distress Scale (SUDS). In June 2026, Vistagen (搜索) announced topline results showing the single-dose randomized portion 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 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 screening LSAS score of 95 or greater (n=123), fasedienol was nominally statistically significant on the SUDS, with an LS mean change from baseline of -12.8 (plus or minus 3.4 SE) versus -3.7 (plus or minus 3.4 SE) for placebo, a difference in LS means of -9.1 (p=0.036).
Vistagen (搜索) said it is preparing to meet with the FDA during the current quarter to consider a proposed new registrational Phase 3 clinical trial of fasedienol in social anxiety disorder (搜索). The company has stated its belief that its fasedienol development program could support a potential New Drug Application submission to the FDA for the acute treatment of social anxiety disorder.
Study Closure and Data Limitations
Vistagen (搜索) closed the OLE portion of PALISADE-4 in July 2026, prior to the data cut-off, for business reasons after concluding that its clinical program for fasedienol nasal spray has achieved the minimum patient exposures recommended under ICH E1, the international regulatory standard governing safety database exposure recommendations for drugs intended for long-term treatment of non-life-threatening conditions. Because of the closure, not all participants had the opportunity to reach the four-month observation point, and the efficacy findings are exploratory, drawn from an open-label extension without blinding or a concurrent control arm.
Fasedienol is Vistagen (搜索)'s most advanced intranasal pherine product candidate. The company describes pherines as a class of rapid-onset neurocircuitry-focused intranasal candidates 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's other pherine candidates are itruvone for major depressive disorder (搜索) and refisolone (搜索) for vasomotor symptoms (搜索) due to menopause.