VistaGen’s CNS drug fails in Phase II depression study

15th November 2019 (Last Updated December 24th, 2019 06:41)

VistaGen Therapeutics has reported that AV-101 did not meet the primary endpoint in a Phase II clinical trial of patients with major depressive disorder (MDD).

VistaGen’s CNS drug fails in Phase II depression study
ELEVATE involved patients with major depressive disorder in the US. Credit: Małgorzata Tomczak from Pixabay.

VistaGen Therapeutics has reported that AV-101 did not meet the primary endpoint in a Phase II clinical trial of patients with major depressive disorder (MDD).

AV-101 is an antagonist of N-methyl-D-aspartate (NMDA) receptor glycine site. It is formulated as an oral prodrug of 7-chlorokynurenic acid (7-Cl-KYNA) and is being developed to treat various central nervous system (CNS) disorders.

The double-blind, placebo-controlled, multi-centre, sequential parallel comparison design (SPCD) Phase II trial, named ELEVATE, assessed the safety, tolerability and efficacy of 1,440mg a day AV-101 as adjunctive therapy for MDD.

The study enrolled 199 patients who did not experience an adequate response to a stable standard antidepressant therapy dose at 25 sites in the US.

Eligible participants continued their stable dose of a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) during the trial.

The primary efficacy endpoint was the absolute change in the Montgomery-Åsberg Depression Rating Scale (MADRS-10) score of AV-101 from baseline to the end of the therapy period compared to placebo.

According to the data, ELEVATE failed to meet the primary goal, with no difference in the MADRS-10 total score between AV-101 and placebo groups.

Safety analysis showed that AV-101 was well-tolerated, without any psychotomimetic side effects or serious adverse events.

VistaGen Therapeutics CEO Shawn Singh said: “While we are disappointed with the top-line results of the study, it is possible that efficacy may have been compromised by either insufficient transport of AV-101 across the blood-brain barrier or subsequent inadequate concentrations of its active metabolite, 7-Cl-KYNA, in the brain.”

Singh added that the company will further analyse the Phase II data for AV-101’s effects on other endpoints and pharmacokinetics.

In addition to depression, the drug candidate is being studied for the treatment of epilepsy, neuropathic pain, levodopa-induced dyskinesia, and suicidal ideation.