RICHMOND, Calif., March 8, 2012 /PRNewswire/ -- Sangamo
BioSciences, Inc. (Nasdaq: SGMO) announced that new data from its
program to develop a 'functional cure' for HIV/AIDS were
described in two presentations at the 19th Conference on
Retroviruses and Opportunistic Infections (CROI), held in
Seattle from March 5 to March 8, 2012.
"These data differentiate SB-728-T from other novel therapies as
a feasible approach to controlling HIV/AIDS," said Ronald Mitsuyasu, M.D., Professor of Medicine,
David Geffen School of Medicine at
UCLA and a principal investigator in
Sangamo's SB-728-T studies. "The results suggest that
SB-728-T has a positive effect on immune health of HIV-infected
patients and this effect is persistent for over a year in some
subjects. Most importantly, SB-728-T treatment provides
HIV-resistant T-cells that are capable of mounting an immune
response to an inflammatory event in lymphoid tissues and has
yielded encouraging effects on HIV viral load when antiretroviral
drugs are withdrawn during a treatment interruption."
"These data add to our understanding of the positive viral load
changes in SB-728-T-treated subjects, and suggest that an early
cytokine burst may initiate the dramatic and prolonged increase in
CD4 counts observed following SB-728-T treatment," said
Dale Ando, M.D., Sangamo's vice
president of therapeutic development and chief medical officer.
"They also confirm that SB-728-T meets key requirements for our
strategy for a 'functional cure' for HIV, by demonstrating durable
engraftment and prolonged trafficking and dynamic immunological
responsiveness in the gut mucosa. Together, these data
further validate our strategy for the continued development of this
ZFP Therapeutic as a 'functional cure' for HIV in two ongoing Phase
2 clinical trials designed to extend the observation of a
statistically significant correlation between levels of bi-allelic
modification of CD4 T cells and viral load reductions during
treatment interruptions in HIV infection. The first study builds on
the approximate doubling of bi-allelic engraftment that can be
achieved in CCR5 delta-32 heterozygotes and seeks to confirm the
occurrence of aviremia during treatment interruption as
observed in one such patient in our Phase 1 program. The
other clinical trial will examine the ability of a lymphopenic
preconditioning regimen to enhance bi-allelic engraftment, and
reduce viral load during treatment interruption, in
non-CCR5-mutated HIV subjects."
Clinical Trial Data Summary
Abstract # 155 "Induction of Acquired CCR5
Deficiency with Zinc Finger Nuclease (ZFN) Modified Autologous CD4
T-cells (SB-728-T) Correlates with Increases in CD4 Count and
Effects on Viral Load (VL) in HIV-infected Subjects"
-Thursday, March 8, 2012
21 HIV-infected subjects were enrolled in Phase 1 clinical studies
at the University of Pennsylvania and
in California (SB-728-902) and
received a single dose of SB-728-T (5 to 30 billion cells). All
subjects were taking highly active antiretroviral therapy (HAART)
and had stably controlled undetectable levels of HIV in their
blood. Subjects were classified into two groups based on
their CD4+ T-cell counts: one group of 15 subjects, with CD4+
T-cell counts below 500 cells/ ul designated Immune Non-Responders
(INR), and a second group of six subjects with CD4+ T-cell counts
of greater than 450 cells/ ul designated Immune Responders
(IR). One month after SB-728-T treatment, six subjects in the
INR group enrolled in the University of
Pennsylvania study underwent a 12-week treatment
interruption (TI) of their HAART.
The studies evaluated safety and tolerability, changes in CD4+
T-cell counts and the ratio of CD4+ to CD8+ T-cells as well as
persistence of SB-728-T in the blood and trafficking of these
ZFN-modified cells into gut-associated lymph tissue. In addition,
viral DNA and changes in viral load (VL), as measured by HIV-RNA,
were measured during the TI in the six INR subjects.
These studies demonstrated:
- During the TI, the viral load, as measured by HIV-RNA levels,
initially increased as expected in all six subjects.
Subsequently, a 0.8 to >2.0-log reduction in VL from peak
achieved during the TI was observed in 3 of 6 subjects with the
highest estimated circulating levels of cells with biallelic
modification of their CCR5 gene. In one subject
(Subject 205) VL decreased to undetectable levels such that the
subject was aviremic at the end of the TI period. This
subject entered the study carrying the natural CCR5 delta-32
mutation on one copy of his CCR5 gene resulting in an estimated
percentage of biallelically-disrupted CCR5 genes that was twice
that of subjects entering the study with wild-type CCR5 genes.
- Control of HIV-RNA (suppression of VL) correlates significantly
(p