Nasal Spray Fasedienol Provides Rapid Social Anxiety Benefit in Phase 3 Trial

An investigative nasal spray designed to treat social anxiety disorder (SAD) achieved late-stage clinical trial endpoints including improved Subjective Units of Distress Scale (SUDS) scores in patients undergoing a public speaking challenge, according to biopharmaceutical company Vistagen.¹

The company’s product, fasedienol (previously PH94B), has achieved top-line phase 3 trial results that investigators believe may support its eventual US Food and Drug Administration (FDA) approval to treat patients with SAD—a common condition that which currently lacks any specifically indicated therapeutics.

What’s more, the drug may provide fast-acting benefit to patients with SAD encountering an anxiety-inducing situation.

Fasedienol is a first-in-class pherine nasal spray designed to provide rapid-onset benefit for SAD through a novel proposed mechanism of action that regulates olfactory-amygdala neural circuits associates with fear and anxiety and attenuates the tone of the sympathetic autonomic nervous system, according to Vistagen. The product provides therapeutic response without mechanisms generally associated with available antidepressants, including systemic distribution, GABA-A receptor potentiation or direct brain neuron activity.

Shawn Singh, chief executive officer of Vistagen, praised the capability of the nasal spray product to deliver a novel option to anxiety care market—specifically for the treatment of a condition which impacts an estimated 25 million-plus Americans.

“As a new class of medicines, our pherine nasal spray pipeline holds the potential to transform the treatment landscape across numerous therapeutic areas,” Singh said. “At the head of that class, fasedienol’s potential, as demonstrated in this phase 3 trial, sets the stage for the first fundamentally new class of medicine for individuals living with SAD in more than 20 years.”

The PALISADE-2 trial is a randomized, double-blind, placebo-controlled phase 3 clinical trial assessing the efficacy, safety and tolerability of acute fasedienol administration in adult patients with SAD across multiple care centers. Fasedienol’s benefit for SAD was assessed by patient-reported SUDS scores during a simulated public speaking challenge designed to provoke anxiety.

Eligible adult patients had a diagnosis of SAD at baseline, as well as a Liebowitz Social Anxiety Scale (LSAS) score of ≥70. The 24-item, self-rated LSAS was designed by former Columbia University psychiatrist Michael R. Liebowitz, MD, director and founder of the Anxiety Disorders Clinic at the New York State Psychiatric Institute; it provides a score for social anxiety on a scale of 0 – 95, with greater scores indicating severity.

The total enrollment of US participants was 141 patients, due in part to a pause in enrollment following the third-party review of achieved top-line results in PALISADE-1. “Although the results of the independent interim analysis indicated that continuation of PALISADE-2 would not be futile, Vistagen determined the best course of action was to close the PALISADE-2 study given the expense, time and methodological complexities involved in resuming PALISADE-2,” the company stated.

Investigators reported the PALISADE-2 trial met its primary efficacy endpoint of difference in mean SUDS score during the public speaking challenge from baseline to treatment with fasedienol among the 70 treated patients versus the 71 patients in the control arm. Mean SUDS score reduced by 13.8 among the fasedienol arm, versus -8.0 among the control arm, indicating a significantly greater difference of -5.8 (P = .015).

Fasedienol also achieved the secondary end point of statistically significant improvement in proportion of clinician-assessed patients reporting “very much less anxious” or “much less anxious” status on the Clinical Global Impression – Improvement (CGI-I) scale after treatment (37.7%) versus those administered placebo (21.4%; P = .033).

Additionally, patient-reported anxiety was significant improved among the fasedienol arm. Investigators observed a significant improvement in proportion of patients identifying as “very much less anxious” or “much less anxious” on the Patient’s Global Impression of Change (PGI-C) scale with fasedienol (40.6%) than those with placebo (18.6%; P = .003).

What’s more, greater than one-third of all treated patients (35.7%) achieved a ≥20-point improvement in patient-assessed SUDS scores baseline to treatment, versus just 18.6% of placebo-treated patients (P = .02).

Regarding safety and tolerability, fasedienol was not associated with any severe or serious adverse events; no events occurred in more than 2% of the treatment arm.

Liebowitz, an investigator for the potential treatment, praised the rapid and significant clinical benefit observed per SUDS score in the fasedienol arm, “indicating a single administration has the potential to reduce anxiety symptoms during an anxiety-provoking situation.”

“A future phase 3 study involving multiple administrations of fasedienol over several weeks on a patient-tailored, as-needed basis will build on the body of evidence now demonstrated in PALISADE-2 and multiple phase 2 studies,” Liebowitz said in the statement. “Fasedienol could be an optimal treatment for social anxiety patients given its ability to be used acutely to reduce anxiety while helping to reduce SAD severity over time.”

Vistagen stated additional data analysis from the phase 3 trial is ongoing; the company intends to present the peer-reviewed results of the stated outcomes at upcoming scientific meetings.

References

1. ^{Vistagen. Vistagen Announces Positive Top-Line Results from Phase 3 PALISADE-2 Trial of Fasedienol (PH94B) Nasal Spray in Social Anxiety Disorder. Press release. Published August 7, 2023. https://www.vistagen.com/news-releases/news-release-details/vistagen-announces-positive-top-line-results-phase-3-palisade-2}