Sangamo BioSciences Initiates Phase 2 Clinical Trial of Treatment for Amyotrophic Lateral Sclerosis (ALS)
Posted : Wed, 03 Sep 2008 11:02:23 GMT
Author : Sangamo BioSciences, Inc.
Category : Press Release





SB-509 to be Evaluated in Repeat-Dosing Study in Subjects with ALS RICHMOND, Calif., Sept. 3

RICHMOND, Calif., Sept. 3 /PRNewswire-FirstCall/ -- Sangamo BioSciences,
Inc. (Nasdaq: SGMO) announced today that it has opened a Phase 2 clinical
trial (SB-509-801) to evaluate its drug, SB-509, in subjects with ALS, a
progressive, degenerative motor-neuron disease for which there are limited
treatment options and no cure.

Sangamo's drug, SB-509, is an injectable formulation of a plasmid encoding
a zinc finger DNA-binding protein transcription factor (ZFP TF(TM)) designed
to upregulate the expression of the gene encoding vascular endothelial growth
factor (VEGF-A). SB-509 is also in three additional Phase 2 clinical trials
for diabetic neuropathy and stem cell mobilization. VEGF-A has been shown to
have nerve protection properties as well as promoting nerve, blood vessel and
muscle growth.

In ALS, the motor nerves comprised of nerve cells in the brain and spinal
cord that control the body's voluntary muscles, gradually degenerate. As the
nerve cells begin to die, the muscles weaken and shrink. As the disease
progresses, patients gradually lose the use of their limb and neck muscles,
ultimately becoming paralyzed and unable to breathe without assistance. Fifty
percent of patients with ALS die within three to five years of diagnosis.
Currently, there is only one approved drug for ALS; Riluzole has been
demonstrated to slow the progression of this debilitating disease with only
modest clinical benefit, extending the survival of ALS patients by
approximately three months.

"Initiation of a Phase 2 clinical study of SB-509 in subjects with a motor
neuron and muscle disease such as ALS is an obvious next step in the
evaluation of this novel therapeutic," stated Dale Ando, M.D., Sangamo's vice
president of therapeutic development and chief medical officer. "The drug is
designed to activate the expression of the subject's own VEGF-A gene. There is
mounting pre-clinical and clinical evidence to support a correlation between
reduced VEGF-A levels and progression of this life-threatening disease. Our
Phase 1 clinical studies of SB-509 in diabetic neuropathy have shown that the
drug is well tolerated. Data from this clinical study and pre-clinical studies
in animal models of nerve damage reveal positive effects of SB-509 on motor
nerve function and muscle composition. Similar effects on motor nerves and
muscles in these patients may slow the progression of ALS by preserving nerve
function and improving muscle fiber composition and strength."

The Phase 2 trial (SB-509-801) is a randomized repeat-dosing, open-label,
multi-center study designed to evaluate the effect of intramuscular
administration of SB-509 on the progression of the disease in subjects with
ALS, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) a
validated rating instrument for monitoring the progression of disability in
patients with ALS. Efficacy of SB-509 will be evaluated by comparing the rate
of ALS disease progression in subjects treated with SB-509 in this study to
historical placebo controls. In addition to gathering data on safety and
tolerability of SB-509 in subjects with ALS, data will be collected to
evaluate the effect of SB-509 on additional clinical measures. These measures
include Forced Vital Capacity (FVC), a test of lung function; Neurophysiologic
Index (NI), a measure of neurologic impairment; Manual Muscle Test (MMT), a
test of muscle strength; and survival. Finally, the study will also evaluate
stem cell mobilization in subjects with ALS receiving SB-509.

"We are pleased to meet our goal of beginning a Phase 2 clinical trial in
ALS this year and are very excited to begin these proof of principle studies,"
said Edward Lanphier, Sangamo's president and CEO. "VEGF has been demonstrated
to have a fundamental role in the growth and health of blood vessels, nerves
and muscle and we believe that our approach of using a ZFP TF to stimulate the
expression of all of the natural forms of a subject's own VEGF-A gene may have
potential therapeutic benefit for a variety of neurodegenerative conditions
including ALS."


About the Study, SB-509-801

A total of 40 subjects with ALS will be enrolled in this trial and
randomized into one of two treatment cohorts. The first cohort of 35 subjects
will receive 60 mg of SB-509 in a divided dose into muscles in the arm, leg,
and along the spine on both sides of the body. A second cohort of 5 subjects
will receive 60 mg of SB-509 in a divided dose into the muscles in the lower
limb in both legs. Each subject will receive a total of two treatments of 60
mg of SB-509 intramuscularly three months apart on Day 0 and Day 90. The study
will be carried out over 11 months, including 2 months for screening, 3 months
for two study treatments, and 6 months of follow-up after administration of
the final dose. Individuals interested in participating in this trial should
visit http://www.clinicaltrials.gov/ or http://www.alsa.org


About Amyotrophic Lateral Sclerosis (ALS)

More than 30,000 Americans have ALS, according to the ALS Association, a
nonprofit organization that supports ALS research and public and patient
education about the disease. 3,000 to 5,000 new cases of the disease are
diagnosed every year. Men and women of all ethnic and racial groups are
equally affected, usually between the ages of 40 and 70. The disease attacks
the motor nerves, nerve cells in the brain and spinal cord that control the
body's voluntary muscles. As the motor nerves begin to die, the muscles weaken
and shrink. Early symptoms of ALS may include unusual tiredness and
clumsiness, muscle weakness, slurred speech, and difficulty swallowing. As the
disease progresses, patients gradually lose the use of their hands, arms,
legs, and neck muscles, ultimately becoming paralyzed. They can speak and
swallow only with great difficulty. About half of people with ALS die within
three to five years of diagnosis.


About Sangamo

Sangamo BioSciences, Inc. is focused on the research and development of
novel DNA-binding proteins for therapeutic gene regulation and modification.
The most advanced ZFP Therapeutic(TM) development program is currently in
Phase 2 clinical trials for evaluation of safety and clinical effect in
patients with diabetic neuropathy and ALS. Other therapeutic development
programs are focused on cancer, HIV/AIDS, neuropathic pain, nerve
regeneration, Parkinson's disease and monogenic diseases. Sangamo's core
competencies enable the engineering of a class of DNA-binding proteins known
as zinc finger DNA-binding proteins (ZFPs). By engineering ZFPs that recognize
a specific DNA sequence Sangamo has created ZFP transcription factors
(ZFP TF(TM)) that can control gene expression and, consequently, cell
function. Sangamo is also developing sequence-specific ZFP Nucleases (ZFN(TM))
for gene modification. Sangamo has established strategic partnerships with
companies outside of the human therapeutic space including Dow AgroSciences,
Sigma-Aldrich Corporation and several companies applying its ZFP Technology to
enhance the production of protein pharmaceuticals. For more information about
Sangamo, visit the company's web site at http://www.sangamo.com.

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