GERMANTOWN, Md., March 12, 2015 /PRNewswire/ -- Neuralstem,
Inc. (NYSE MKT: CUR) announced top line data from the Phase II
trial of NSI-566 spinal cord-derived neural stem cells under
development for the treatment of amyotrophic lateral sclerosis
(ALS). The study met primary safety endpoints. The maximum
tolerated dose of 16 million transplanted cells and the surgery was
well tolerated.
Secondary efficacy endpoints at nine months post-surgery
indicate a 47% response rate to the stem cell treatment, as
measured by either near-zero slope of decline or positive slope of
ALSFRS score in seven out of 15 patients and by either a near-zero
decline, or positive strengthening, of grip strength in seven out
of 15 patients. Grip strength is an indicator of direct muscle
strength of the lower arm. ALSFRS is a standard clinical test used
to evaluate the functional status of ALS patients. The average
ALSFRS score for responders at 9 months after treatment was 37.
Non-responders scored an average of 14. These scores represent 93%,
versus 35%, of the baseline score retained, respectively, by the
responders versus non-responders at 9 months, which is a
statistically significant difference. As measured by an average
slope of decline of ALSFRS, responders' disease progression was
-0.007 point per day, while non-responders' disease progression was
-0.1 per day, which was again statistically significant. Lung
function as measured by Seated Vital Capacity shows that responder
patients remained within 94% of their starting scores, versus 71%
for non-responder patients. The trial met its primary safety
endpoints. Both the surgery and cells were well-tolerated, with one
patient experiencing a surgical serious adverse event.
"In this study, cervical intervention was both safe and
well-tolerated with up to 8 million cells in 20 bilateral
injections," said Karl Johe, PhD,
Neuralstem Chief Scientific Officer. "The study also demonstrated
biological activity of the cells and stabilization of disease
progression in a subset of patients. As in the first trial, there
were both responders and non-responders within the same cohort,
from patients whose general pre-surgical presentation is fairly
similar. However, we believe that through the individual
muscle group measurements, we may now be able to differentiate the
responders from the non-responders.
"Our therapy involves transplanting NSI-566 cells directly into
specific segments of the cord where the cells integrate into the
host motor neurons. The cells surround, protect and nurture the
patient's remaining motor neurons in those various cord segments.
The approximate strength of those remaining motor neuron pools can
be measured indirectly through muscle testing of the appropriate
areas, such as in the grip strength tests. We believe these
types of endpoints, measuring muscle strength, will allow us to
effectively predict patients that will respond to treatment, adding
a sensitive measure of the therapeutic effects after treatment.
Testing this hypothesis will be one of the primary goals of our
next trial." The full data is being compiled into a manuscript for
publication.
"We believe the top-line data are encouraging," said
Eva Feldman MD, PhD, Director of the
A. Alfred Taubman Medical Research Institute and Director of
Research of the ALS Clinic at the University
of Michigan Health System, and an unpaid consultant to
Neuralstem. "We were able to dose up to 16 million cells in 40
injections, which we believe to be the maximum tolerated
dose. As in the first trial, the top-line data show disease
stabilization in a subgroup of patients. Perhaps equally as
important, we believe the top-line data may support a method of
differentiating responders from non-responders, which we believe
will support our efforts as we move into the next, larger
controlled trial expected to begin this summer."
"The top-line data look very positive and encouraging. If this
proportion of patients doing well after treatment can be
corroborated in future therapeutic trials, it will be better than
any response seen in any previous ALS trials," said site principal
investigator, Jonathan D. Glass, MD,
Director of the Emory ALS Center. "Elucidating which factors define
a patient who may have a therapeutic response to the stem cell
treatment will be the next key challenge. We are hopeful that a set
of predictive algorithms can be established to help pre-select the
responders in our future trials."
"We were very excited to participate as a site in this clinical
trial," said Merit Cudkowicz, MD, Chief of Neurology,
Massachusetts General Hospital and Co-Chair of the Northeast ALS
Consortium (NEALS). "We are hopeful with respect to the top-line
results and we need to move swiftly and safely forward to confirm
the responder effect and identify people who might benefit from
this treatment approach."
The open-label, dose-escalating trial treated 15 ambulatory
patients, divided into 5 dosing cohorts, at three centers,
Emory University Hospital in
Atlanta, Georgia, the ALS Clinic
at the University of Michigan Health
System, in Ann Arbor, Michigan,
and Massachusetts General Hospital in Boston, Massachusetts, and under the direction
of principal investigator (PI), Eva
Feldman, MD, PhD, Director of the A. Alfred Taubman Medical
Research Institute and Director of Research of the ALS Clinic at
the University of Michigan Health
System. Dosing increased from 1 million to 8 million cells in the
cervical region of the spinal cord. The final trial cohort also
received an additional 8 million cells in the lumbar region of the
spinal cord.
The company anticipates commencing a later-stage, multicenter
trial of NSI-566 for treatment of ALS in 2015. Neuralstem has
received orphan designation by the FDA for NSI-566 in ALS.
About Neuralstem
Neuralstem's patented technology enables the production of
multiple types of central nervous system stem cells in FDA GMP
commercial quantities. These stem cells are under development for
the potential treatment of central nervous system diseases and
conditions.
Neuralstem's ability to generate human neural stem cell lines
for chemical screening has led to the discovery and patenting of
compounds that Neuralstem believes may stimulate the brain's
capacity to generate neurons, potentially reversing pathologies
associated with certain central nervous system (CNS) conditions.
The company has completed Phase Ia and Ib trials evaluating
NSI-189, its first neurogenic small molecule product candidate, for
the treatment of major depressive disorder (MDD), and is expecting
to initiate a Phase II study for MDD and a Phase Ib study for
cognitive deficit in Schizophrenia in 2015.
Neuralstem's first stem cell product candidate, NSI-566, a
spinal cord-derived neural stem cell line, is under development for
treatment of amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). The primary endpoints
were met in Phase II. In addition to ALS, NSI-566 is also in a
Phase I trial in chronic spinal cord injury at UC San Diego School
of Medicine. NSI-566 is also in clinical development to treat
neurological diseases such as ischemic stroke and acute spinal cord
injury.
Neuralstem's next generation stem cell product, NSI-532.IGF,
consists of human cortex-derived neural stem cells that have been
engineered to secrete human insulin-like growth factor 1 (IGF-1).
In animal data presented at the Congress of Neurological Surgeons
2014 Annual Meeting, the cells rescued spatial learning and memory
deficits in an animal model of Alzheimer's disease.
For more information, please visit www.neuralstem.com or connect
with us on Twitter, Facebook and LinkedIn
Cautionary Statement Regarding Forward Looking Information:
This news release contains "forward-looking statements" made
pursuant to the "safe harbor" provisions of the Private Securities
Litigation Reform Act of 1995. Such forward-looking
statements relate to future, not past, events and may often be
identified by words such as "expect," "anticipate," "intend,"
"plan," "believe," "seek" or "will." Forward-looking statements by
their nature address matters that are, to different degrees,
uncertain. Specific risks and uncertainties that could cause our
actual results to differ materially from those expressed in our
forward-looking statements include 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 September 30,
2014.
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SOURCE Neuralstem, Inc.