What could become the first fast-acting drug for social anxiety is working its way through late-stage clinical trials.
Everyday antidepressants are currently the only approved drugs for the condition, but they don’t provide immediate relief from anxiety spikes. Vistagen hopes to offer a better option with its investigational phase 3 drug, fasedienol, which was granted fast track status by the FDA in 2019.
The on-demand spray, which users can take moments before a stressful event, belongs to a new drug class called pherines. It targets nasal receptors using a low microgram dose, ultimately triggering a reaction in the neurocircuitry in the amygdala, the primitive part of the brain that regulates fear response, said Shawn Singh, Vistagen’s CEO.
Showing clinical promise
Although the company said the drug missed its primary endpoint in an initial phase 3 trial due to variability created by the “unprecedented clinical development environment” during the COVID-19 pandemic, it hit the mark in a subsequent phase 3 PALISADE-2 trial. The study included 141 patients and found that those who used the nasal spray saw a statistically significant improvement in a patient-reported measure of anxiety called the Subjective Units of Distress Scale.
Reviewers also rated nasal spray users as less anxious during a simulated public speaking challenge compared with participants who took the placebo — 37.7% versus 21.4%.
“A key hallmark of the drug’s mechanism is that it does not require systemic or full body absorption,” Singh said.
The drug doesn’t bind to abuse-liability receptors in the brain, which reduces the potential for addiction. And it notched fewer side effects than many antidepressants that can trigger weight gain and suicidal thoughts, or impact sex drive. Most commonly, trial participants on fasedienol experienced headaches, according to Singh.
When the drug wears off after about an hour, users can maintain the effect by taking up to four to six additional doses per day, said Singh.
“It's really important to have that flexibility without the unwanted consequences of the current meds. They want to maintain perfect cognition. They don't want to be sedated. They certainly don't want to become addicted,” Singh said.
"Any amount of penetration we’re able to achieve is going to affect a lot of lives.”
Shawn Singh
CEO, Vistagen
The drug is now in a third phase 3 trial, and, if all goes as planned, the company could submit a new drug application in the first part of 2026. It also hopes to test the nasal spray in children with social anxiety.
In addition to fasedienol, Vistagen is testing other pherines to treat depression, menopausal hot flashes, wasting syndrome and cognitive and psychomotor impairment due to mental fatigue. Its pipeline includes an investigational drug, AV-101, an oral antagonist of the glycine site of the N-methyl-D-aspartate receptor, for central nervous system disorders. And the FDA granted AV-101 a fast track designation for major depressive disorder and as a non-opioid treatment for neuropathic pain.
Although other companies are also working on new treatments for social anxiety, including a negative allosteric modulator from Bionomics and a pharmaceutical-grade cannabidiol product from EmpowerPharm, Singh said fasedienol would still offer a unique option.
“There isn't anybody in a late stage, let alone anybody with the safety profile and rapid onset effect that we've seen,” Singh said. “That doesn't mean we're going to conquer the entire universe. However, it is important to know that any amount of penetration we're able to achieve is going to affect a lot of lives.”
