The mazda pharma Guide 15th Julu - 21st july 2013 | Page 68

�PHARMACEUTICAL ARTICLE

Selected, preliminary data from the MERIT
research abstract stated,“ This current study
complete remission( CR) or a complete remission
trial is expected to be presented at the ALK company-
investigates whether mesencephalic astrocyte-derived
with incomplete blood count recovery( Cri).
sponsored symposium on June 23 during the EAACI-
neurotrophic factor( MANF) inhibits oxygen-glucose
“ The initiation of this randomized phase II
WAO( European Academy of Allergy and Clinical
deprivation( OGD)-induced cell damage and
trial is an important milestone in the clinical
Immunology – World Allergy Organization)
inflammatory cytokine secretion by suppressing
development of Pracinostat,” said Robert D Mass,
Congress. This announcement does not impact ALK ' s
endoplasmic reticulum stress in rat primary
MD, chief medical officer of MEIPharma.“ The
financial guidance for 2013. ALK is a research-driven
astrocytes. We found that MANF alleviated OGD-
results from the pilot study reported at ASH were
global pharmaceutical company focusing on allergy
induced astrocyte damage and rescued the cell
very exciting and helped to inform the design of this
prevention, diagnosis and treatment.
viability, and the upregulation of GRP78
more robust, placebo-controlled trial. Now, our goal
POSITIVE RESULTS ON MANF
( endoplasmic reticulum( ER) stress marker) and NF-
is to build on these preliminary data and get a more
NEUROPROTECTIVE PROPERTIES
? B p65( one of the central mediators of
precise estimate of the clinical benefit of Pracinostat
DEMONSTRATED IN PRECLINICAL STUDY:
proinflammatory pathways) induced by OGD were
in combination with standard-of-care.”
Amarantus BioScience Holdings, Inc., a
significantly reduced by preincubation of MANF. In
The multi-centre phase II trial is expected to
biotechnology company discovering and developing
addition, the increases of secretion and mRNA
enroll 100 patients with a one-to-one randomization.
treatments and diagnostics for diseases associated
expression levels of the proinflammatory cytokines
Completion of enrollment is anticipated by June 2014
with neurodegeneration and apoptosis, has reported
IL-1ß, IL-6, and TNF-a in astrocytes induced by
with topline data in December 2014. The primary
positive neuroprotective properties for its MANF
OGD were significantly suppressed by MANF.”
endpoint of the study is complete remission( CR).
therapeutic were demonstrated in a preclinical
MANF( Mesencephalic-Astrocyte-derived
Secondary endpoints include overall response rate
research study conducted by the Department of
Neurotrophic Factor) is believed to have broad
( CR + CRi + PR), haematologic improvement, duration
Orthopaedics at Qilu Hospital of Shandong
potential because it is a naturally-occurring protein
of response, progression-free survival, rate of
University, in Jinan, China.
produced by the body for the purpose of reducing and
leukaemic transformation, overall survival and safety.
Specifically, a published abstract of the study
preventing apoptosis( cell death) in response to injury
The trial is being conducted in collaboration with the
concluded,“ These findings demonstrate that MANF
or disease, via the unfolded protein response. By
Sarah Cannon Research Institute; Dr Guillermo
shows the potential to alleviate cell damage and
manufacturing MANF and administering it to the
Garcia-Manero of the MD Anderson Cancer Centre is
inflammation in rat primary astrocytes by suppressing
body, Amarantus is seeking to use a regenerative
the principal investigator.
ER( endoplasmic reticulum) stress, indicating that
medicine approach to assist the body with higher
“ This represents the first in a series of phase II
MANF plays an important role in astrocyte
quantities of MANF when needed. Amarantus is the
studies we have planned for Pracinostat in the months
inflammation and functioning and may suggest a
front-runner and primary holder of intellectual
ahead,” said Daniel P Gold, Ph. D., president and
promising strategy for neuroprotection in the central
property( IP) around MANF, and is initially focusing
chief executive officer of MEI Pharma.“ We believe
nervous system.
on the development of MANF-based protein
that Pracinostat truly has the potential to become a
“ The findings from the study at Shandong
therapeutics. MANF ' s current lead indication is
best-in-class drug. We intend to execute a
University are consistent with the results we obtained
Parkinson ' s disease with additional focus on
comprehensive development programme in order to
in our own research with MANF on rat models for
Traumatic Brain Injury( TBI). Future indications may
realize its full potential and determine the most
Parkinson ' s disease, which were reported in March
include myocardial infarction and certain rare and
efficient registration path forward.”
2013,” said John W. Commissiong, Ph. D., chief
ultra-rare orphan diseases for which MANF is
In addition to the randomized phase II clinical
scientific officer of Amarantus.“ We are very pleased
currently being evaluated.
trial in frontline MDS, the Company is also preparing
that independent research is contributing to the
Amarantus is a development-stage
for the initiation of two open-label phase II trials of
further understanding of MANF. The protective
biotechnology company and focussed on developing
Pracinostat: one in combination with Vidaza in
activity demonstrated by this independent work
certain biologics surrounding the intellectual property
frontline acute myeloid leukaemia( AML) in the fall
clearly suggests MANF may have utility in the
and proprietary technologies it owns to treat and / or
of 2013 and the other in combination with Vidaza or
treatment of conditions such as stroke, post-stroke
diagnose Parkinson ' s disease, Traumatic Brain Injury,
Dacogen( decitabine) in patients with refractory MDS
recovery, Traumatic Brain Injury and concussion, as
Ischemic Heart Disease and other human diseases.
soon thereafter.
well as having relevance to the use of MANF in
PHASE II TRIAL OF PRACINOSTAT IN
Pracinostat is an orally available histone
Parkinson ' s disease. We continue to conduct
COMBO WITH VIDAZA TO TREAT
deacetylase( HDAC) inhibitor that has been tested in
additional experiments with MANF in support of a
MYELODYSPLASTIC SYNDROME:
MEI
a number of phase I and exploratory phase II clinical
planned Investigational New Drug( IND) application
Pharma, Inc., an oncology company focused on the
trials in advanced haematologic disorders and solid
to the FDA.”
clinical development of novel therapies for cancer,
tumour indications in both adult and paediatric
An abstract of the research report titled
has dosed its first patient in a phase II clinical trial of
patients. Pracinostat has been generally well tolerated
“ Mesencephalic Astrocyte-Derived Neurotrophic
its lead drug candidate Pracinostat in combination
in more than 200 patients to date, with readily
Factor Inhibits Oxygen-Glucose Deprivation-Induced
with Vidaza( azacitidine) in patients with previously
manageable side effects that are often associated with
Cell Damage and Inflammation by Suppressing
untreated intermediate-2 or high-risk myelodysplastic
drugs of this class, such as fatigue. Pracinostat has
Endoplasmic Reticulum Stress in Rat Primary
syndrome( MDS). The randomized, double-blind trial
exhibited pharmacokinetic properties that compare
Astrocytes,” was e-published in the Journal of
is designed to evaluate the safety and efficacy of
favorably to other oral HDAC inhibitors, including
Molecular Neuroscience. Glucose and oxygen
Pracinostat compared to placebo when combined
Zolinza( vorinostat), which is approved by the FDA
deprivation is a common factor in conditions
with Vidaza, a drug approved by the US Food &
for the treatment of cutaneous T-cell lymphoma. In
involving reduced blood flow to the brain. This
Drug Administration( FDA) for the treatment of
addition to the evidence of clinical activity observed
places energy stress on cells such as astrocytes, which
MDS.
in combination with Vidaza in patients with MDS,
then become damaged, functionally impaired or even
Results from an earlier pilot study of
Pracinostat has demonstrated single-agent activity in
die. Release of inflammatory mediators from stressed
Pracinostat in combination with Vidaza in patients
AML, including two CRs out of 14 patients( 14 per
astrocytes causes further damage to neurons, with
with intermediate-2 or high-risk MDS were presented
cent) in a dose-escalation trial, with durable
resulting neurological impairment. The work from
at the American Society of Haematology( ASH)
responses persisting up to 362 days. MEIPharma
Shandong University suggests MANF may protect
Annual Meeting in December 2012 showed an
owns exclusive worldwide rights to Pracinostat.
against such neurological damage by suppressing
overall response rate of 89 per cent( eight out of
these pro-inflammatory changes in astrocytes. The
nine), including seven patients who achieved either a
68 THE MAZADA PHARMA GUIDE ●15 July- 21 July 2013