Vistagen’s social anxiety disorder (SAD) drug candidate has flunked another phase 3 trial. But with a post hoc subpopulation analysis linking fasedienol to a nominal statistically significant improvement, the biotech plans to talk to the FDA about a path to approval based on a single future pivotal study.
In December, Vistagen said intranasal fasedienol was statistically no better than placebo at improving a self-reported measure of distress in the phase 3 PALISADE-3 trial in SAD. The setback drove William Blair analysts to assign “a substantially higher-risk profile” to Vistagen’s PALISADE-4 study, reflecting doubts about whether “fasedienol is an active agent for the acute treatment of SAD.”
On Tuesday, Vistagen’s PALISADE-4 readout gave fasedienol skeptics fresh ammunition. The 238-subject study found fasedienol was statistically no better than placebo at reducing anxiety symptoms during a simulated anxiety-provoking public speaking challenge, causing the trial to miss its primary endpoint. The study also missed its secondary endpoints.
“Those results certainly were disappointing,” Vistagen CEO Shawn Singh said on a call with investors to discuss the data. “However, our multiple post hoc analyses of the data in patients with very severe social anxiety disorder, amounting to slightly over half of the patients randomized in the trial, demonstrate significant findings we believe are important from clinical and regulatory perspectives.”
The case for further development rests on a post hoc analysis in a subpopulation of 123 patients with very severe social anxiety. The analysis linked fasedienol to nominally significant reductions in anxiety symptoms, as measured on the Subjective Units of Distress Scale, or SUDS.
Fasedienol was numerically more effective in the subpopulation than in the overall trial, with SUDS scores falling 12.8 points and 9.5 points, respectively. Limiting the analysis to the subpopulation had a bigger effect on the placebo data. Having linked placebo to an 11.4-point reduction in the overall trial, Vistagen reported a 3.7-point decline in SUDS score in the subpopulation analysis.
Vistagen saw “notable differences between the mean and median placebo responses,” indicating that a relatively small number of “extreme values” in the control cohort influenced the overall result, Angel Angelov, M.D., chief medical officer at Vistagen, said on the call.
Based on the analysis and data from other fasedienol studies, Vistagen plans to talk to the FDA about running a single phase 3, multidose outpatient trial to support approval. The plan, which is based on draft guidance that the FDA released last week, would see Vistagen pivot from developing fasedienol for the treatment of acute symptoms to focusing on addressing SAD over time.
Vistagen’s share price fell 70% to 23 cents in premarket trading. The company’s cash runway extends into 2027.