The Mazda Pharma Guide 7th October to 13th October | Page 68

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PHARMACEUTICAL ARTICLE
STEM CELLS TO TREAT TEN DIFFERENT
DISEASE INDICATIONS : Advanced Cell
Technology, Inc. (ACT), a leader in the field of
regenerative medicine, has filed an Investigational
New Animal Drug (INAD) application with the US
Food and Drug Administration (FDA) to test its
proprietary "off-the-shelf" mesenchymal stem cells
(MSC) in a range of different disease indications.
The studies will evaluate the safety and
efficacy of ACT's pluripotent stem cell-derived
MSCs in ten spontaneous disease models in dogs,
which are similar to various human inflammatory
and immune-mediated diseases. While these
companion animal studies represent research
intended for ultimate licensure of veterinary
therapeutics, ACT anticipates that the trial results
may be relevant to its path to clinical trials in
human patients and may provide a more robust
assessment of safety and therapeutic endpoints than
what can be obtained from inbred rodent models.
The INAD is directed to ten canine disorders
corresponding to hepatitis, glomerulonephritis,
osteoarthritis, Crohn's disease, inflammatory bowel
disease, spinal cord/ disc disease,
meningoencephalitis, hemolytic anaemia,
pancreatitis and sepsis.
"This INAD filing extends our ongoing
work with w orld experts in veterinary and
regenerative medicine," said Robert Lanza, MD,
chief scientific officer of ACT. "Preliminary studies
in rodents have shown that our hESC-derived
MSCs possess unique biological and therapeutic
properties, and can dramatically impact a spectrum
of diseases ranging from lupus to multiple sclerosis.
In addition to veterinary applications, these large
animal studies may help inform and optimize
subsequent human clinical trials that the company
may pursue. We believe the etiology and systemwide effects of naturally-occurring diseases in large
animals, such as dogs, provide an excellent model
of human conditions."
ACT's proprietary MSCs have been
extensively characterized both in vivo and in vitro,
and their effects have been shown to be superior in
animals to those of their bone marrow (BM)derived MSCs counterparts. ACT's proprietary
MSCs are immunoprivileged and therefore, may be
used "off the shelf" in a wide range of clinical
indications. In addition to increased efficacy, hESCMSCs can be expanded to large numbers in vitro
(approximately 30,000 times greater yields per unit
than adult BM sources). Since MSCs are derived
from an inexhaustible starting stem cell line, the
cost and regulatory burden of requiring many
donors is thereby removed, as is the case with the
adult sources of MSCs currently in the clinic.
Having a single, donor-less source of pluripotent
stem cells for manufacturing MSCs also removes
the batch-to-batch variability in potency and the
risk of communicable diseases that comes with
relying on bone marrow or other adult tissue donors
in the current MSC setting.
"The preclinical studies that Dr Lanza and
our team have carried out can now be translated
into companion animal studies and, hopefully,
human clinical studies in the not-too-distant
future," said Gary Rabin, chairman and CEO of

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ACT. "In addition to advancing our corporate
strategy to apply our cutting edge stem cell
technologies to bring human therapies to market,
this step into companion animals also elucidates
new potential market opportunities for our
company. The veterinary market is a large and
exciting market in which we may have a significant
opportunity to apply our leadership in regenerative
medicine. The development of these therapies may
permit veterinarians and pet owners to manage pets'
medical needs safely and effectively, and could
result in longer and improved quality of life for
pets." Advanced Cell Technology, Inc., is a
biotechnology company applying cellular
technology in the field of regenerative medicine.
PHASE III STUDY OF DRISAPERSEN TO
TREAT PATIENTS WITH DUCHENNE
MUSCULAR DYSTROPHY FAILS TO MEET
PRIMARY ENDPOINT : GlaxoSmithKline
(GSK), one of the world's leading research-based
pharmaceutical and healthcare companies, and
Prosensa, a Dutch biotechnology company, have
reported that GSK's phase III clinical study of
drisapersen, an investigational anti-sense
oligonucleotide, for the treatment of Duchenne
Muscular Dystrophy (DMD) patients with an
amenable mutation, did not meet the primary
endpoint of a statistically significant improvement
in the 6 Minute Walking Distance (6MWD) test
compared to placebo.
A total of 186 boys were randomised to
this double-blind, placebo-controlled study
(DMD114044) and received drisapersen at a dose
of 6mg/kg/week (N=125) or placebo (N=61) via
subcutaneous injection over 48 weeks. The
difference in 6MWD (mean (CI) 10.33m (-14.65,
35.31), p=0.415) between drisapersen and placebo
groups did not reach statistical significance. There
was no treatment difference in key secondary
assessments of motor function: 10-meter walk/run
test, 4-stair climb and North Star Ambulatory
Assessment. The most commonly reported adverse
events included injection site reactions (78 per cent
for drisapersen vs 16 per cent for placebo) and renal
adverse events (including subclinical proteinuria;
46 per cent for drisapersen vs 25 per cent for
placebo). No patients had thrombocytopenia.
Full evaluation of the benefit-to-risk
profile of drisapersen treatment across all studies is
anticipated to be completed by year end. This may
include analyses of pooled results from various
drisapersen studies.
“We appreciate that these results will be
disappointing for boys with DMD and their
families. We would like to sincerely thank all those
who participated in the study for their
commitment,” commented Carlo Russo, senior vice
president, head of GSK Rare Diseases Research &
Development. “We are committed to evaluating the
outcome of this study in the context of the overall
development programme with experts in the field,
and we expect such evaluation to help inform our
next steps for drisapersen. It is our hope that
progress will be made in an effort to help boys with
DMD.”
“While we are disappointed that this study
did not meet its primary endpoint, we remain

committed to the overall programme and will
continue to work closely with GSK.” said Hans
Schikan, chief executive officer of Prosensa. “With
no long term disease modifying therapies available
for DMD patients, research and development of
possible treatment options is of critical importance
for boys and their families affected by this
debilitating disease.”
Results have been submitted for
presentation at forthcoming scientific meetings and
will also be published in a scientific peer-reviewed
journal.
DRISAPERSEN IS NOT APPROVED OR
LICENSED FOR USE ANYWHERE IN THE
WORLD : Drisapersen, (previously
GSK2402968/PRO051) an antisense
oligonucleotide, which induces exon skipping of
exon 51, is currently in late stage development for
DMD.
GSK obtained an exclusive worldwide
license to develop and commercialise drisapersen
from Prosensa in 2009. Drisapersen has been
designated orphan drug status in the EU, US and
Japan. In June 2013, drisapersen was granted
Breakthrough Therapy designation by the US Food
and Drug Administration.
The overall clinical programme comprises
three early phase studies (PRO051-01, PRO051-02
and DMD114673) and three double-blind, placebocontrolled studies (DMD114117, DMD114876 and
DMD114044). Phase II results from DMD 114117
were presented at Cold Spring Harbor in April 2013
and are posted on www.gskclinicalstudyregister.com. The phase II results of
DMD114876 will be presented at DIA/FDA
oligonucleotide meeting, Sept 25-27, 2013,
Washington, USA and other scientific congress
meetings this year. The clinical programme also
includes an open-label extension study
DMD114349 for boys completing DMD114117 and
DMD114044.
The dystrophin gene is the largest gene in
the body, consisting of 79 exons. Exons are small
sequences of genetic code which lead to the
manufacture of sections of protein. In DMD, when
certain exons are mutated/deleted, the RNA cannot
read past the fault. This prevents the rest of the
exons being read, resulting in a non-functional
dystrophin protein and the severe symptoms of
DMD.
RNA-based therapeutics, specifically
antisense oligonucleotides inducing exon skipping,
are currently in development for DMD. This
technology uses synthetic antisense
oligonucleotides to skip an exon next to a deletion
and thereby correct the reading frame, enabling the
production of a novel dystrophin protein. Up to
13% of boys with DMD have dystrophin gene
mutation/deletions amenable to an exon 51 skip.
GlaxoSmithKline – – is committed to
improving the quality of human life by enabling
people to do more, feel better and live longer.
Prosensa is engaged in the discovery and
development of RNA-modulating therapeutics for
the treatment of genetic disorders.

THE MAZADA PHARMA GUIDE q
7 October - 13 October 2013