California’s VistaGen Therapeutics announced topline data from its Phase III PALISADE-1 trial, showing that PH94B, its nasal spray candidate for anxiety, depression and other central nervous system disorders, fell short of its primary endpoint.
PALISADE-1 was a randomized, double-blinded and parallel study that enrolled more than 200 participants with a social anxiety disorder (SAD) across the United States. The trial compared PH94B with a nasal spray placebo to assess if it could induce self-reported feelings of anxiety during a public speaking challenge.
PH94B’s overall impact, as measured by the Subjective Units of Distress Scale, was not significantly better than that of the placebo.
As a consolation, VistaGen’s candidate was generally well-tolerated, causing no new safety concerns or severe side effects. The company finds PH94B’s safety profile encouraging and plans to rechannel the candidate into other indications.
“While the results of PALISADE-1 are not consistent with prior positive results from Phase 2 trials of PH94B in social anxiety disorder, we remain committed to transforming the treatment landscape for those living with anxiety, depression, and other central nervous system disorders,” Shawn Singh, chief executive officer of VistaGen, said in a statement.
“As part of this commitment, our team will continue to pursue PH94B’s potential as a new treatment option for multiple anxiety disorders — including for both acute treatment for social anxiety disorder in our ongoing PALISADE-2 Phase 3 trial and for continued use in our ongoing Phase 2 trial in adjustment disorder with anxiety,” Singh added.
VistaGen was pinning much of its hopes on PH94B. In May, Singh told BioSpace that the company wanted to provide an alternative to benzodiazepines, a common prescription for anxiety. However, when used excessively, benzodiazepines can lead to dependence and, ultimately, substance abuse, which could harm the user’s overall health and wellbeing.
“We know there’s a benzo epidemic,” Singh said. “There are a lot of potential downstream worries associated with benzos. There’s cognitive impairment, there’s sedation, there’s the risk of abuse, as well as liability for long-term use. We need to provide alternatives.”
But with PH94B’s failure in SAD, VistaGen is now back to the exploratory Phase II stage, looking for signals that its nasal spray drug might be effective against various anxiety disorders, including adjustment disorder, post-traumatic stress disorder, postpartum anxiety and generalized anxiety disorder.
Aside from PH94B, the company is also working on PH10, another nasal spray-based candidate meant for neuropsychiatric conditions related to depression. In March last year, PH10 set itself apart from benzodiazepines by showing in a preclinical study that its mechanism of action did not directly involve GABA-A receptors.
Currently, VistaGen is planning a Phase IIb trial to evaluate PH10 as a standalone therapy for major depressive disorder. The candidate is also awaiting exploratory Phase IIa studies for treatment-resistant depression, postpartum depression and suicidal ideation.
Both PH94B and PH10 deliver proprietary pherines, a family of neurosteroid compounds designed to rapidly elicit their effects. Both candidates act through chemosensory receptors in the nose, activating a group of neurons in the amygdala, the brain region associated with stress and anxiety. Because they work directly at the site where they are applied, PH94B and PH10 do not need systemic uptake; they aren’t detectable in the blood and do not interfere with other medications.