Vistagen (Nasdaq: VTGN) confirmed that its PALISADE-3 Phase 3 clinical trial evaluating fasedienol nasal spray for acute treatment of social anxiety disorder (SAD) remains on track to deliver topline data in the fourth quarter of 2025. The company also announced that topline results for its PALISADE-4 Phase 3 trial are expected in the first half of 2026.
"We are very encouraged by the progress of our PALISADE-3 trial, which remains on track for a topline readout in the fourth quarter of this year, and our PALISADE-4 trial, for which we expect topline results in the first half of 2026," said Shawn Singh, President and Chief Executive Officer of Vistagen. "Patient and physician enthusiasm for our PALISADE trials continues to be strong, and we remain focused on meticulous patient recruitment."
Novel Mechanism of Action Differentiates Fasedienol
Fasedienol represents a potential first-in-class, investigational neurocircuitry-focused pherine nasal spray designed to have rapid onset with a novel mechanism of action that is differentiated from all currently approved anxiety medications. The drug is designed to regulate the olfactory-amygdala neural circuits of fear and anxiety and attenuate the tone of the sympathetic autonomic nervous system without systemic absorption, potentiation of GABA-A receptors, or binding to neurons in the brain.
The U.S. FDA has granted Fast Track designation for the development of fasedienol for the acute treatment of SAD, recognizing the significant unmet medical need in this patient population.
Addressing a Significant Medical Need
Social anxiety disorder is a highly prevalent, serious, and sometimes life-threatening psychiatric mental health disorder affecting over 30 million adults in the U.S. With onset typically early in life, usually during adolescence, SAD persists for many years thereafter, with a reported mean duration of about 20 years.
The disorder can manifest acutely when triggered by anxiety-provoking social and performance situations during which individuals with SAD experience extreme anxiety, distress, fear, and impairment due to their feelings of embarrassment, judgment, humiliation, negative evaluation, and scrutiny. The disorder can significantly disrupt family and social life, diminish self-esteem, and hinder work performance. Anxiety associated with SAD often results in avoidance of everyday interactions and opportunities in academic, social, and vocational settings and an increased risk of serious and life-threatening co-morbid depression, substance abuse, suicidal ideation, and suicide.
PALISADE Phase 3 Program Design
The ongoing clinical trials in Vistagen's U.S. registration-directed PALISADE Phase 3 Program for fasedienol include the PALISADE-3 and PALISADE-4 Phase 3 trials and a small Phase 2 repeat dose study, which is being conducted at the FDA's request to further elucidate fasedienol's dose response and mechanism of action.
PALISADE-3 and PALISADE-4 are multi-center, randomized, double-blind, placebo-controlled Phase 3 trials designed similarly to PALISADE-2 to evaluate the efficacy, safety, and tolerability of the acute administration of fasedienol to relieve anxiety symptoms in subjects with SAD induced by a public speaking challenge conducted in a clinical setting.
The ongoing trials involve the same public speaking challenge study design as the successful PALISADE-2 Phase 3 trial, as well as certain protocol and operational enhancements related to site training, surveillance and subject selection. These strategic enhancements were designed with the objective of replicating the success of PALISADE-2.
Regulatory Pathway Forward
Vistagen reported positive results from its PALISADE-2 Phase 3 trial of fasedienol for acute treatment of SAD in 2023. The company believes either PALISADE-3 or PALISADE-4, if successful, together with the positive results from PALISADE-2, may establish substantial evidence of the effectiveness of fasedienol in support of a potential fasedienol New Drug Application (NDA) submission to the U.S. FDA for the acute treatment of SAD.
Pherine Technology Platform
Vistagen is leveraging a deep understanding of nose-to-brain neurocircuitry to develop and commercialize a broad and diverse pipeline of clinical-stage product candidates from a new class of intranasal therapies called pherines. Pherines specifically and selectively bind as agonists to peripheral receptors on human nasal chemosensory neurons, and are designed to rapidly activate olfactory bulb-to-brain neurocircuits believed to regulate brain areas involved in behavior and autonomic nervous system activity.
They are 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. The company's neuroscience pipeline also includes an oral prodrug with potential to impact certain neurological conditions involving the NMDA receptor.
