GERMANTOWN, Md., June 18, 2014 /PRNewswire/ -- Neuralstem,
Inc. (NYSE MKT: CUR) announced that final data from the
Neuralstem NSI-189 Phase Ib study in major depressive disorder
(MDD) was presented yesterday at the American Society of Clinical
Psychopharmacology Annual Meeting in Hollywood, Florida. NSI-189 is Neuralstem's
first-in-class, lead neurogenic small molecule compound, shown to
promote neurogenesis in vitro. In animal studies, NSI-189 resulted
in a 20% increase in hippocampal volume. In a presentation called,
"A Phase Ib Randomized, Double-Blind, Placebo-Controlled,
Multiple-Dose Escalation Study Evaluating the Effects of NSI-189
Phosphate, A Neurogenic Compound, in Patients with Major Depressive
Disorder (MDD)," Marlene Freeman,
MD, Medical Director, Clinical Trials Network and Institute,
Massachusetts General Hospital, and Associate Professor of
Psychiatry, Harvard Medical School,
reported clinically meaningful reduction in cognitive and
depressive symptoms across all measures in depressed patients on
active therapy against the control group. These positive gains in
both cognitive function and diminishment of depression symptoms
continued for the duration of the trial, eight weeks after the
28-day treatment had stopped. The abstract can be found on page 73
of the abstract book
http://ascpmeeting.org/wp-content/uploads/2014/05/ASCP-Oral-Abstract-Book-Online.pdf
Specifically, a large effect was seen in all four scales
employed in the study that are commonly used to assess clinical
levels of depression and improvement: CGI-I (Clinical Global
Impression Improvement); MADRS (Montgomery-Asberg Depression
Scale); SDQ (Symptoms of Depression Questionnaire) and CPFQ
(Massachusetts General Cognitive and Physical Functioning
Questionnaire). In particular, the Symptoms of Depression
Questionnaire (SDQ) showed 0.02 p value at day 28 of dosing, with
large effect size (Cohen's d = 0.90), and 0.03 p value at day
84, 8 weeks after cessation of drug administration, also with large
effect size
(Cohen's d = 1.10). Also in cognitive testing, measured by the
CPFQ, the study recorded 0.01 p value with large effect size
(Cohen's d = 0.94) at day 28 and 0.01 p value also with large
effect size (Cohen's d = 1.20) at day 84, 8 weeks after cessation
of drug administration. Effect size is a statistical term measuring
the overall effect of the treatment. A value above .80 is
considered to be a large effect.
"I am glad to see our study selected for the oral presentation
at this prestigious conference. This further validates the paradigm
shift we are seeing from a serotonin-based to neurogenesis-based
theory of depression," said Karl
Johe, PhD, Neuralstem's Chairman and Chief Scientific
Officer. "We know from extensive preclinical studies that NSI-189
has a highly specific effect in the hippocampus, a well-known
neurogenic region in adults. Now in our human study, despite the
historical difficulty of showing drug effects in depression trials,
NSI-189 produced remarkably robust and long-lasting improvement in
patients at multiple doses compared to placebo.
In particular, I would like to highlight two unusual findings
that have not been seen in clinical trials of current depression
treatments. First, the large and significant effect size of the
antidepressant activity, as measured by MADRS and SDQ scores,
continued for the full duration of the monitoring period, eight
weeks after NSI-189 administration had been ceased. Secondly,
in addition to its antidepressive effects, NSI-189 showed a
significant effect size in cognitive function improvement. This
cognitive improvement also continued for eight weeks after the last
dose.
"These observations are consistent with our hypothesis that
NSI-189 is altering the fine structures within the hippocampus in a
manner that is long-lasting," Dr. Johe concluded. "This gives us
encouragement that NSI-189 may modify progression of cognitive
impairment diseases as well as depression."
"Treating depression through neurogenesis opens up an entirely
new avenue of treatment for patients who are suffering with these
diseases and need new and better treatment options," said lead
study author, Maurizio Fava, MD,
Executive Vice Chair, Department of Psychiatry, Executive Director,
Clinical Trials Network and Institute, Massachusetts General
Hospital, "This study represents the first demonstration of a
promising new compound being developed towards that goal and we
look forward to confirming these results in the next
trial."
"We wish to thank our collaborators at Parexel and at
Massachusetts General Hospital for helping us design, execute and
analyze this trial, particularly Dr. Maurizio Fava for his help and Dr. Marlene Freeman for making the presentation,"
said Richard Garr, Neuralstem's
President and CEO. "This successful trial marks an important
milestone for the company, as our small molecule regenerative
medicine platform has now demonstrated proof-of-concept functional
recovery in patients and will soon join our cell therapy platform
in later stage clinical trials. Our plans are to start a
larger NSI-189 Phase II trial to confirm this strong data by the
end of this year."
About the Trial
In a double-blinded, placebo controlled Phase Ib trial, 24
patients with recurrent major depressive disorder (MDD), divided
into three cohorts of eight each, received ascending doses of
NSI-189 for 28 days. Cohort 1 received 40 mg once daily. Cohort 2
received 40 mg twice daily. Cohort 3 received 40 mg three times
daily. In each cohort, two randomly selected, blinded patients
received placebo instead of active treatment. The patients were
tested at regular intervals along established clinical depression
and cognitive scales of assessment.
About Major Depressive Disorder
Major depressive disorder (MDD), also called major
depression, is characterized by a combination of symptoms that
interfere with a person's ability to function normally. MDD affects
approximately 14.8 million American adults and is the leading cause
of disability in the U.S. for ages 15-44, according to the National
Institute of Mental Health. While most treatments modulate brain
neurotransmitter levels to treat brain chemistry, new research
suggests that brain physiology could also be involved. Depressed
patients have reduced volume in the hippocampus, a part of the
brain that generates new neurons. Neuralstem believes that
stimulating the generation of new neurons in the hippocampus could
potentially address the pathology of the depression
itself.
About Neuralstem
Neuralstem's patented technology enables the production of
neural stem cells of the brain and spinal cord in commercial
quantities, and the ability to control the differentiation of these
cells constitutively into mature, physiologically relevant human
neurons and glial cells. Neuralstem's NSI-566 spinal cord-derived
stem cell therapy is in Phase II clinical trials for amyotrophic
lateral sclerosis (ALS), often referred to as Lou Gehrig's disease. Neuralstem has been
awarded orphan status designation by the FDA for its ALS cell
therapy.
In addition to ALS, the company is also targeting major
central nervous system conditions with its NSI-566 cell therapy
platform, including spinal cord injury and ischemic stroke. The
company has received FDA approval to commence a Phase I safety
trial in chronic spinal cord injury.
Neuralstem also maintains the ability to generate stable
human neural stem cell lines suitable for systematic screening of
large chemical libraries. Through this proprietary screening
technology, Neuralstem has discovered and patented compounds that
may stimulate the brain's capacity to generate neurons, possibly
reversing pathologies associated with certain central nervous
system conditions. The company has completed a Phase I safety trial
evaluating NSI-189, its first neurogenic small molecule product
candidate, for the treatment of major depressive disorder
(MDD). Additional indications might include traumatic brain
injury (TBI), Alzheimer's disease, and post-traumatic stress
disorder (PTSD).
For more information, please visit www.neuralstem.com or
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Cautionary Statement Regarding Forward Looking
Information:
This news release may contain forward-looking statements
made pursuant to the "safe harbor" provisions of the Private
Securities Litigation Reform Act of 1995. Investors are cautioned
that such forward-looking statements in this press release
regarding potential applications of Neuralstem's technologies
constitute forward-looking statements that involve risks and
uncertainties, including, without limitation, risks inherent in the
development and commercialization of potential products,
uncertainty of clinical trial results or regulatory approvals or
clearances, need for future capital, dependence upon collaborators
and maintenance of our intellectual property rights. Actual results
may differ materially from the results anticipated in these
forward-looking statements. Additional information on potential
factors that could affect our results and other risks and
uncertainties are detailed from time to time in Neuralstem's
periodic reports, including the annual report on Form 10-K for the
year ended December 31, 2013 and Form
10Q, for the period ended March 31,
2014.
SOURCE Neuralstem, Inc.