Full Press Release Details
Reports Topline Phase 2 Results for AV-101 as an Adjunctive
Treatment of Major Depressive Disorder
SOUTH SAN FRANCISCO, Calif., November 14, 2019 VistaGen
Therapeutics (NASDAQ: VTGN), a clinical-stage
biopharmaceutical company developing new generation medicines for
central nervous system (CNS) diseases and disorders with high unmet
need, today announced topline results from the ELEVATE study, a
Phase 2 study of AV-101, its NMDA (N-methyl-D-aspartate) receptor
glycine site antagonist, as an adjunctive treatment of major
depressive disorder (MDD). In this study, the AV-101 treatment arm
did not differentiate from placebo on the primary endpoint (change
in the Montgomery- sberg Depression Rating Scale (MADRS-10)
total score compared to baseline). As in prior clinical studies,
AV-101 was well tolerated, with no psychotomimetic side
effects or serious adverse
we are disappointed with the topline 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. We will continue to examine the full
dataset from this study to evaluate effects on other endpoints and
pharmacokinetics, as well as consider both the upcoming results
from a target engagement study and the potential impact of
compelling new evidence from recent preclinical studies
demonstrating substantial concentration increases of AV-101
(approximately a 7-fold increase) and 7-Cl-KYNA (approximately a
35-fold increase) in the brain in rodent studies when AV-101 is
administered in combination with probenecid, an FDA-approved anion
transport inhibitor used adjunctively with numerous
well-established medications to enhance efficacy, said
Shawn Singh, Chief Executive Officer of
The rigorous conduct of the study makes us confident that
AV-101, at the concentrations used, was not effective, but will
also allow us to interrogate the database without the confound of
excessive placebo responses. There is a clear need for new and safe
agents that can be used for augmentation among depressed patients
with inadequate response to antidepressant therapies,
said Dr. Maurizio Fava,
Psychiatrist-in-Chief of Massachusetts General
remain excited by and focused on continued execution of our Phase 3
program for PH94B in social anxiety disorder and our Phase 2
program for PH10 in major depressive disorder, added Mr.
Singh. Each of these first-in-class compounds is further
along in development than AV-101, as they have already demonstrated
clinical proof of concept in Phase 2 studies, and, thus, in 2020,
we will be proceeding into Phase 3 and Phase 2b studies,
respectively. During 2020, we also will review the total body of
preclinical and clinical work on AV-101, across all indications
(depression, epilepsy, levodopa-induced dyskinesia, neuropathic
pain and suicidal ideation), as well as additional preclinical
studies involving AV-101 and probenecid, and then determine the
most appropriate path forward for potential clinical development of
AV-101. We deeply appreciate the patients, their caregivers, and
the investigators who supported the ELEVATE study, including Dr.
Fava as principal investigator. Our determination to develop safe,
life-changing new generation medications for mental health
disorders and neurological conditions with high unmet need remains
ELEVATE study was a Phase 2, double-blind, placebo-controlled,
multi-center, sequential parallel comparison design (SPCD) study
that evaluated the safety, tolerability, and efficacy of AV-101 as
an adjunctive treatment in patients with MDD who had an inadequate
response to a stable dose of standard antidepressant therapy
(either a selective serotonin reuptake inhibitor (SSRI) or a
serotonin norepinephrine reuptake inhibitor (SNRI)). The study
randomized 199 patients across 25 clinical research centers in the
United States. Consistent with the SPCD, the study was
conducted in two, two-week sequential stages. Eligible subjects
continued receiving their SSRI or SNRI antidepressant at a stable
dose for the duration of the study. Patients were randomly assigned
(1:3) to AV-101 1440 mg/day or placebo in Stage 1. Placebo
non-responders (defined as a < 50% reduction from baseline in
MADRS-10 total score at the end of Stage 1) were re-randomized
(1:1) in Stage 2 to receive AV-101 1440 mg/day or placebo for 2
weeks. The primary efficacy endpoint was the absolute change from
baseline to end of treatment in the MADRS-10 score of AV-101
compared to placebo, both in combination with ongoing therapy with
an SSRI or SNRI. Treatment differences from Stage 1 and Stage 2
were combined as weighted averages.
Therapeutics is a clinical-stage biopharmaceutical company
developing new generation medicines for CNS diseases and disorders
where current treatments are inadequate, resulting in high unmet
need. VistaGen's pipeline is
focused on clinical-stage CNS drug candidates with a differentiated
mechanism of action, an exceptional safety profile in all clinical
studies to date, and therapeutic potential in multiple large and
growing CNS markets. For more information, please
visit www.vistagen.com and
connect with VistaGen on Twitter, LinkedIn and Facebook.
Forward-Looking Statements
release contains various statements concerning VistaGen's future
expectations, plans and prospects, including without limitation,
our expectations regarding development and commercialization of our
three drug candidates: (i) AV-101 for MDD, neuropathic pain,
epilepsy, dyskinesia associated with levodopa therapy for
Parkinson's disease and suicidal ideation; (ii) PH94B for
social anxiety disorder and other anxiety disorders; and (iii) PH10
for MDD. In addition, statements concerning the Company's
future expectations may include statements regarding intellectual
property and commercial protection of our drug candidates. Each of
these statements constitute forward-looking statements for the