VistaGen's Antidepressant Fails in Difficult-to-Treat Patients Trial

When major depressive disorder (MDD) does not respond to at least two different types of antidepressant treatments in a moderate-to-severe depressive episode, it is reclassified as treatment-resistant depression or TRD. South San Francisco-based VistaGen Therapeutics’ AV-101 failed to meet its primary efficacy endpoints for TRD in a Phase II clinical trial.

AV-101 is an oral NMDA receptor glycine site antagonist that is a potential treatment for multiple central nervous system (CNS) indications with a high unmet medical need. The drug was received Fast Track designation by the U.S. Food and Drug Administration (FDA) for adjunctive treatment for MDD and as a non-opioid therapy for neuropathic pain.

In the 19-patient Phase II clinical trial sponsored and conducted by the U.S. National Institute of Mental Health (NIMH), AV-101 did not show significant change from baseline in patients compared to placebo. The key objective of the trial wasn’t efficacy, but to evaluate the drug’s safety in TRD patients, and this was consistent with the drug’s effects in Phase I trials. It was very well-tolerated with no ketamine-like psychological side effects or safety concerns.

“Although this small NIMH monotherapy study did not meet its primary endpoint in this very difficult-to-treat TRD population, we remain firmly committed to developing novel treatments for those suffering from MDD,” stated Shawn Singh, VistaGen’s chief executive officer. “In contrast to the NIMH study, our ongoing ELEVATE study is designed to evaluate AV-101 as a novel adjunctive therapy in a significantly different population of MDD patients, namely those whose current depressive episode is less than 2 years. ELEVATE is on track and we will announce top-line results later this year.”

In the NIMH trial, TRD patients tapered off all antidepressant treatments, including adjunctive atypical antipsychotics, for 2 to 5 weeks. They then stayed off medication for another two weeks before receiving AV-101.

The patients were randomized at that point to receive either a daily dose of AV-101 for 14 days in a dosing of 1080 mg for 7 days followed by 1440 mg for 7 days, or a placebo for 14 days. After a 2- to 3-week period called “washout,” where they cleared the drugs from their systems, they then crossed over to the opposite study arm.

VistaGen plans to present detailed data at a scientific conference in the future.

On April 1, VistaGen announced additional data from a positive pilot Phase III trial of PH94B, a possible first-in-class neuroactive nasal spray being evaluated for the treatment of social anxiety disorder (SAD). The trial looked at 22 patients for four weeks. Patients who received the drug had a significantly greater drop in average peak Subjective Units of Distress scores compared to placebo within one week of treatment. There were also other evaluation scores, which the patients did well on. The drug’s safety profile was also excellent with no serious adverse events.

The company is preparing for a pivotal Phase III trial as a first-line as-needed (PRN) treatment for SAD.

“Social anxiety disorder is one of the most prevalent mental health conditions in the U.S., affecting as many as 15 million Americans,” stated Michael Liebowitz, developer of the Liebowitz Social Anxiety Scale (LSAS) and Principal Investigator of the study. “In both Phase II and pilot Phase III clinical studies, PH94B was more effective than placebo in the whole sample on the primary outcome measure. In the Phase II trial, which included both public speaking and a social situation challenge, PH94B significantly improved the primary efficacy endpoint within 10 to 15 minutes of self-administration.”

The company’s stocks, however, took a hit at today’s announcement, dropping 44.91% to $0.58.