Geron Corporation (Nasdaq:GERN) announced today that the U.S. Food and
Drug Administration (FDA) has granted clearance of the company’s
Investigational New Drug (IND) application for the clinical trial of
GRNOPC1 in patients with acute spinal cord injury.
The clearance enables Geron to move forward with the world’s first study
of a human embryonic stem cell (hESC)-based therapy in man. Geron plans
to initiate a Phase I multi-center trial that is designed to establish
the safety of GRNOPC1 in patients with “complete” American Spinal Injury
Association (ASIA) grade A subacute thoracic spinal cord injuries.
“The FDA’s clearance of our GRNOPC1 IND is one of Geron’s most
significant accomplishments to date,” said Thomas B. Okarma, Ph.D.,
M.D., Geron’s president and CEO. “This marks the beginning of what is
potentially a new chapter in medical therapeutics – one that reaches
beyond pills to a new level of healing: the restoration of organ and
tissue function achieved by the injection of healthy replacement cells.
The ultimate goal for the use of GRNOPC1 is to achieve restoration of
spinal cord function by the injection of hESC-derived oligodendrocyte
progenitor cells directly into the lesion site of the patient’s injured
spinal cord.”
GRNOPC1, Geron’s lead hESC-based therapeutic candidate, contains
hESC-derived oligodendrocyte progenitor cells that have demonstrated
remyelinating and nerve growth stimulating properties leading to
restoration of function in animal models of acute spinal cord injury (Journal
of Neuroscience, Vol. 25, 2005).
“The neurosurgical community is very excited by this new approach to
treating devastating spinal cord injury,” said Richard Fessler, M.D.,
Ph.D., professor of neurological surgery at the Feinberg School of
Medicine at Northwestern University. “Demyelination is central to the
pathology of the injury, and its reversal by means of injecting
oligodendrocyte progenitor cells would be revolutionary for the field.
If safe and effective, the therapy would provide a viable treatment
option for thousands of patients who suffer severe spinal cord injuries
each year.”
The GRNOPC1 Clinical Program
Patients eligible for the Phase I trial must have documented evidence of
functionally complete spinal cord injury with a neurological level of T3
to T10 spinal segments and agree to have GRNOPC1 injected
into the lesion sites between seven and 14 days after injury. Geron has
selected up to seven U.S. medical centers as candidates to participate
in this study and in planned protocol extensions. The sites will be
identified as they come online and are ready to enroll subjects into the
study.
Although the primary endpoint of the trial is safety, the protocol
includes secondary endpoints to assess efficacy, such as improved
neuromuscular control or sensation in the trunk or lower extremities.
Once safety in this patient population has been established and the FDA
reviews clinical data in conjunction with additional data from ongoing
animal studies, Geron plans to seek FDA approval to extend the study to
increase the dose of GRNOPC1, enroll subjects with complete cervical
injuries and expand the trial to include patients with severe incomplete
(ASIA grade B or C) injuries to enable access to the therapy for as
broad a population of severe spinal cord-injured patients as is
medically appropriate.
Preclinical Evidence of Safety,
Tolerability and Efficacy
Geron submitted evidence of the safety, tolerability and efficacy of
GRNOPC1 to the FDA in a 21,000-page IND application that described 24
separate animal studies requiring the production of more than five
billion GRNOPC1 cells. Included in the safety package were studies that
showed no evidence of teratoma formation 12 months after injection of
clinical grade GRNOPC1 into the injured spinal cord of rats and mice.
Other studies documented the absence of significant migration of the
injected cells outside the spinal cord, allodynia induction (increased
neuropathic pain due to the injected cells), systemic toxicity or
increased mortality in animals receiving GRNOPC1.
In vitro studies have shown that GRNOPC1 is minimally recognized
by the human immune system. GRNOPC1 is not recognized in vitro by
allogeneic sera, NK cells or T cells (Journal of Neuroimmunology, Vol.
192, 2007). These immune-privileged characteristics of the hESC-derived
cells allow a clinical trial design that incorporates a limited course
of low-dose immunosuppression and provide the rationale for an
off-the-shelf, allogeneic cell therapy.
Also included in the IND application were published studies supporting
the utility of GRNOPC1 for the treatment of spinal cord injury. Those
studies showed that administration of GRNOPC1 significantly improved
locomotor activity and kinematic scores of animals with spinal cord
injuries when injected seven days after the injury (Journal of
Neuroscience, Vol. 25, 2005). Histological examination of the
injured spinal cords treated with GRNOPC1 showed improved axon survival
and extensive remyelination surrounding the rat axons. These effects of
GRNOPC1 were present nine months after a single injection of cells. In
these nine-month studies, the cells were shown to migrate and fill the
lesion cavity, with bundles of myelinated axons crossing the injury site.
Production and Qualification of GRNOPC1
GRNOPC1 is produced using current Good Manufacturing Practices (cGMP) in
Geron’s manufacturing facilities. Geron’s GRNOPC1 production process and
clean-room suites have been inspected and licensed by the state of
California. The cells are derived from the H1 human embryonic stem cell
line, which was created before August 9, 2001. Studies using this line
qualify for U.S. federal research funding, although no federal funding
was received for the development of the product or to support the
clinical trial.
Geron’s H1 hESC master cell bank is fully qualified for human use and
was shown to be karyotypically normal and free of measurable
contaminants of human or animal origin. Production of GRNOPC1 from
undifferentiated hESCs in the master cell bank uses qualified reagents
and a standardized protocol developed at Geron over the past three
years. Each manufacturing run of GRNOPC1 is subjected to standardized
quality control testing to ensure viability, sterility and appropriate
cellular composition before release for clinical use. GRNOPC1 product
that has passed all such specifications and has been released is
available for the approved clinical trial. The current production scale
can supply product needs through pivotal clinical trials. The existing
master cell bank could potentially supply sufficient starting material
for GRNOPC1 to commercially supply the U.S. acute spinal cord injury
market for more than 20 years.
Intellectual Property
The production and commercialization of GRNOPC1 is protected by a
portfolio of patent rights owned by or exclusively licensed to Geron.
Patent rights owned by Geron protect key technologies developed at Geron
for the scalable manufacturing of hESCs, as well as the production of
neural cells by differentiation of hESCs. The fundamental patents
covering hESCs are exclusively licensed to Geron from the Wisconsin
Alumni Research Foundation (WARF) for the production of neural cells,
cardiomyocytes and pancreatic islets for therapeutic applications. The
validity of these patents was recently confirmed by the U.S. Patent and
Trademark Office in a re-examination proceeding. Geron funded the
original research at the University of Wisconsin-Madison that led to the
first isolation of hESCs. The production of oligodendrocytes from hESCs
is covered by patent rights exclusively licensed to Geron from the
University of California. These patent rights cover technology developed
in a research collaboration between Geron and University of California
scientists.
Conference Call and Video Webcast
Thomas B. Okarma, Ph.D., M.D., will host a conference call and video
Webcast presentation for investors and the media at 6:00 a.m. PST/9:00
a.m. EST today. Participants can access the conference call via
telephone by dialing 866-783-2145 (U.S.) or 857-350-1604
(international). The passcode is 89631672. The video Webcast
presentation is available at http://phx.corporate-ir.net/phoenix.zhtml?p=irol-eventDetails&c=67323&eventID=2077348.
All participants are encouraged to view Dr. Okarma’s presentation on the
Internet. The video Webcast will also be accessible through a link that
is posted on the home page of Geron’s Web site at http://www.geron.com.
Participants are encouraged to log on at least 15 minutes prior to the
beginning of the presentation in order to download any necessary
software. The video Webcast will be available for replay through
February 23, 2009.
Background information about human embryonic stem cells, GRNOPC1 and the
spinal cord injury clinical trial can be found at http://eon.businesswire.com/news/eon/20090122006356/en.
Geron is developing first-in-class biopharmaceuticals for the treatment
of cancer and chronic degenerative diseases, including spinal cord
injury, heart failure and diabetes. The company is advancing an
anti-cancer drug and a cancer vaccine that target the enzyme telomerase
through multiple clinical trials. Geron is also the world leader in the
development of human embryonic stem (hESC) cell-based therapeutics. The
company has received FDA clearance to begin the world’s first human
clinical trial of a hESC-based therapy: GRNOPC1 for acute spinal cord
injury. For more information, visit www.geron.com.
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 statements in this
press release regarding potential applications of Geron’s human
embryonic stem cell technology 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 Geron’s periodic reports, including the quarterly report
on Form 10-Q for the quarter ended September 30, 2008.
