South San Francisco-based Vistagen Therapeutics (Nasdaq: VTGN) reported topline results on August 6 from an exploratory Phase II study of fasedienol nasal spray in adults with social anxiety disorder (SAD), finding that a repeat dose in adults with social anxiety disorder did not meet its primary efficacy endpoint. The company said prespecified subgroup analyses identified a stronger treatment effect in patients with very severe disease, findings it plans to discuss with the US FDA as it evaluates a potential registrational pathway.
The three-arm, multicenter, randomized, double-blind, placebo-controlled trial (NCT06809179) enrolled 61 adults and compared two sequential 3.2 µg intranasal doses of fasedienol administered ten minutes apart against a single 3.2 µg dose and placebo, using a public speaking challenge to induce acute anxiety. The primary endpoint was the least squares mean change in subjective units of distress (SUDS) score from a baseline speech visit to a randomized speech visit. On this measure, pooled fasedienol (N=40) produced a mean change of -15.0 versus -6.8 for placebo, with a Cohen's d effect size of 0.46; the repeat dose arm (N=19) showed a change of -15.4 (Cohen's d=0.44) and the single dose arm (N=21) showed -14.7 (Cohen's d=0.47). None of these differences reached statistical significance, with p-values ranging from 0.10 to 0.17 across arms; the overall between-group comparison yielded p=0.2 based on the prespecified analysis of covariance model.
More pronounced separation emerged in a prespecified subgroup analysis restricted to patients with very severe SAD, defined by a baseline Liebowitz Social Anxiety Scale (LSAS) score of 95 or above. In this subgroup, pooled fasedienol (N=24) produced a mean SUDS change of -16.2 versus -1.6 for placebo (p=0.04, Cohen's d=0.78), and the single dose arm (N=14) reached p=0.05 (Cohen's d=0.80). The repeat dose arm (N=10) showed a numerically larger change of -17.5 (Cohen's d=0.74) but did not reach nominal significance at p=0.08, which Vistagen attributed to smaller sample size and greater variability. Because the study did not meet its primary endpoint, all subsequent analyses showing significance are classified as nominally statistically significant per the statistical analysis plan. The very severe subgroup finding is consistent with a post-hoc analysis from Vistagen's PALISADE-4 Phase III trial, where patients with LSAS ≥95 also showed nominally significant improvement versus placebo (p=0.036).
Responder rates on the CGI-I and PGI-C secondary endpoints were consistently higher with fasedienol than placebo, particularly among patients with very severe social anxiety. A prespecified exploratory analysis also suggested reduced anticipatory anxiety with pooled and repeat-dose fasedienol, although these findings were nominally significant following the missed primary endpoint.