NEW YORK, Jan. 5, 2018 /PRNewswire/
-- Neurotrope (NASDAQ: NTRP) today announced that a
post-hoc analysis of data from its Phase 2 trial in patients with
advanced Alzheimer's disease (AD) found evidence of improvement in
cognition in patients receiving the 20μg bryostatin regimen who did
not receive memantine, an approved AD treatment, as background
therapy. The findings suggest this investigational drug could
potentially help treat the progression of AD, rather than only its
symptoms. The findings will be presented by Daniel Alkon, MD, President and Chief Scientific
Officer of Neurotrope in a keynote presentation at the Sachs'
Neuroscience Innovation Forum on January
7 in San Francisco.
The follow-on analysis also found that patients in the 20μg
treatment arm showed a sustained improvement in cognition over
baseline compared to the placebo group at week 15 (30 days after
last dose at week 11). These data were observed in the study
population as a whole.
"These findings are intriguing and warrant further study to
confirm whether the observed treatment benefit can be replicated
and enhanced," said Martin R.
Farlow, MD, Vice Chairman for Research in the Department of
Neurology, Indiana University School of
Medicine, Indiana Alzheimer Disease Center, who previously
presented the top-line data from Neurotrope's study at the 2017
Alzheimer's Association International Conference.
Memantine, an NMDA receptor antagonist, is marketed under the
brand names Namenda®, Namenda® XR, and Namzaric® (a combination of
memantine and donepezil) for the treatment of dementia in patients
with moderate-to-severe AD. It has been shown to delay cognitive
decline and help reduce disease symptoms. The interaction between
NMDA function and protein kinase C (PKC) has been well studied, and
the scientific rationale elucidating the interactions are explored
in many peer reviewed publications.
"The discovery that an NMDA inhibitor like memantine may
diminish the effect of bryostatin, a PKC epsilon activator is very
interesting as it is consistent with the proposed mode of action of
bryostatin, and provides an internal control within the trial. This
represents one of the most promising new developments in AD
research and is welcome news following so many heartbreaking
disappointments in the field," said George
Perry, PhD, Semmes Foundation University Chair in
Neurobiology, and Dean of the College of Sciences at The
University of Texas at San Antonio, an
internationally recognized leader in AD research who recently
joined Neurotrope's Board as a Director. "These findings suggest
that, for the first time, we may be able to reverse cognitive
decline and actually improve cognition in people with
moderate-to-severe Alzheimer's disease. It will be important to
further investigate these results with confirmatory studies."
In this exploratory Phase 2 study in 150 patients with advanced
AD, two doses of bryostatin (20μg and 40μg) were compared with
controls to assess safety and preliminary efficacy after 12 weeks
of treatment. The pre-specified primary endpoint, the Severe
Impairment Battery (SIB) used to evaluate cognition in severe
dementia, compared each dose of bryostatin with controls at week 13
in two sets of patients: 1) the modified intent-to-treat (mITT)
population (consisting of all patients who received the study drug
and had at least one efficacy/safety evaluation), and 2) the
Completers population (consisting of those patients within the mITT
population who completed the 13-week assessment). As previously
reported, the 20μg dose was found to be safe and well tolerated,
and showed evidence of sustained improvement in cognition compared
to controls, while the 40μg dose did not show an improvement in
cognition.
The follow-on analysis of the data evaluated SIB scores of
patients at 15 weeks, 30 days after all dosing had been completed.
For the 20μg group, patients in the mITT population (n=34) showed
an overall improvement compared to controls (n=33) of 3.59
(p=0.0503) and in the Completers population (n=34) showed an
overall improvement compared to controls (n=33) of 4.09
(p=0.0293). In summary, patients on the 20μg dose showed a
persistent SIB improvement 30 days after all dosing had been
completed. These p-values and those below are one-tailed.
The post-hoc analysis comparing SIB scores in non-memantine
versus memantine patients found the following:
- At week 15, non-memantine patients in the mITT Group treated
with 20μg (n=14) showed an SIB improvement of 5.88, while the
placebo patients (n=11) showed a decline in their SIB scores of
-0.05 for an overall treatment Δ of 5.93 from baseline
(p=0.0576).
- At week 15, non-memantine patients in the Completers Group
treated with 20μg (n=14) showed an SIB improvement of 6.24, while
the placebo patients (n=11) showed a decline in their SIB scores of
-0.12 for an overall treatment Δ of 6.36 from baseline
(p=0.0488).
- Patients taking memantine as background therapy in the 20μg
(n=20) and control (n=22) groups showed no improvement in SIB
scores.
Neurotrope is planning a confirmatory study in advanced AD
patients not taking memantine as background therapy to evaluate
whether the improvements in SIB scores in those patients can be
replicated. The company is in discussions with a leading academic
institution to design and conduct the trial, which is expected to
begin in the first half of 2018.
"Neurotrope's next clinical trial will focus on
the 20μg dose, which showed evidence of
sustained cognitive improvement in advanced Alzheimer's
disease patients," said Dr. Alkon. "It will be designed to confirm,
with increased power, the increases in SIB scores
observed among memantine-free patients in the recently completed
Phase 2 trial. The company has the financial resources required to
complete the planned study."
About Bryostatin
Bryostatin-1 is a protein kinase C epsilon (PKCɛ) activator that
works through synaptic growth factors, as well as anti-amyloid and
anti-tangle signaling pathways in the brain. It has been shown in
preclinical efficacy studies to induce the growth of mature
synapses in the brain and prevent neuronal death. Thus,
Bryostatin-1 introduces a fundamentally different biological
mechanism of action with the potential for longer lasting effects
than the other currently available therapies. Bryostatin-1 is the
first PKCε modulator to be tested in a Phase 2 clinical study
for patients suffering from advanced AD — a difficult to treat
population.
The rationale for researching this novel mechanism in AD results
from in vitro and in vivo models of AD demonstrating
that modulation of PKCε by Bryostatin-1 enhances synaptogenesis and
prevents neuronal death. As synaptic loss is tightly
correlated with cognitive impairment in AD, this attribute of the
molecule made bryostatin an intriguing candidate for additional
investigation in dementia. Furthermore, preclinical studies also
demonstrated bryostatin reduces toxic Aß levels, prevents plaque
formation, inhibits tau phosphorylation, and enhances
cognition. Thus, the multimodal effects of this first PKCε
modulator offer a potential new mechanism to study in AD with the
ultimate goal to slow or prevent the progression of
disease.
About Neurotrope
Neurotrope is at the forefront of developing a new approach to
combating AD and other neurodegenerative diseases. The
Company's world-class science offers the potential to realize a
paradigm shift to overcome one of today's most challenging clinical
problems — finding a way to slow or even prevent the progression of
AD.
In addition to the Company's Phase 2 trial of bryostatin-1 in
advanced AD, Neurotrope has also conducted preclinical studies of
bryostatin as a potential treatment for Fragile X Syndrome,
Niemann-Pick Type C disease and Rett Syndrome—three rare genetic
diseases for which only symptomatic treatments are currently
available. The FDA has granted Orphan Drug Designation to
Neurotrope for Bryostatin-1 as a treatment for Fragile X
Syndrome. Bryostatin-1 has already undergone testing in more
than 1,500 people in cancer studies, thus creating a large safety
data base that will further inform clinical trial designs in
AD.
Forward-Looking Statements
Any statements contained in this press release that do not
describe historical facts may constitute forward-looking
statements. These forward-looking statements include statements
regarding the Phase 2 study and further studies, and continued
development of use of Bryostatin-1 for Alzheimer's dementia and
other cognitive diseases. Such forward-looking statements are
subject to risks and uncertainties and other influences, many of
which the Company has no control over. These statements are subject
to the risk that further analyses of the Phase 2 data may lead to
different interpretations of the data than the analyses conducted
to date and/or may identify important implications of the Phase 2
data that are not reflected in these statements. Clinical trial
data are subject to differing interpretations, and regulatory
agencies, medical and scientific experts and others may not share
the Company's views of the Phase 2 data. There can be no assurance
that the clinical program for Bryostatin-1 will be successful in
demonstrating safety and/or efficacy that we will not encounter
problems or delays in clinical development, or that Bryostatin-1
will ever receive regulatory approval or be successfully
commercialized. Actual results and the timing of certain events and
circumstances may differ materially from those described by the
forward-looking statements as a result of these risks and
uncertainties. Additional factors that may influence or cause
actual results to differ materially from expected or desired
results may include, without limitation, the Company's inability to
obtain adequate financing, the significant length of time
associated with drug development and related insufficient cash
flows and resulting illiquidity, the Company's patent portfolio,
the Company's inability to expand the Company's business,
significant government regulation of pharmaceuticals and the
healthcare industry, lack of product diversification, availability
of the Company's raw materials, existing or increased
competition, stock volatility and illiquidity, and the
Company's failure to implement the Company's business plans or
strategies. These and other factors are identified and described in
more detail in the Company's filings with the SEC, including the
Company's Annual Report on Form 10-K for the year ended
December 31, 2016 and on Form 10-Q
for the quarter ending September 30,
2017. The Company does not undertake to update these
forward-looking statements.
Please visit www.neurotropebioscience.com for further
information.
Contact information:
Investors
Jeffrey Benison, Director of Corporate Communications
Neurotrope Bioscience, Inc.
(m) 516.286.6099
(e) jbenison@neurotropebioscience.com
Media
James Heins
Senior Vice President
ICR Healthcare
(m) 203.856.2121
(e) james.heins@icrinc.com
Related Links
http://www.neurotropebioscience.com
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SOURCE Neurotrope, Inc.