- The first two patients treated at the 3e13 vg/kg dose level
rapidly achieved normal, sustained Factor VIII (FVIII) levels with
no reported bleeding events and no factor usage for as long as 24
weeks of follow-up
- The two patients more recently treated at the 3e13 vg/kg dose
level demonstrated FVIII activity kinetics that appear consistent
with the first two patients in this dose cohort at similar early
time points
- SB-525 showed dose-dependent increases in FVIII activity levels
across all dose cohorts evaluated
- FDA recently granted regenerative medicine advanced therapy
(RMAT) designation for SB-525 gene therapy to treat severe
hemophilia A
Sangamo Therapeutics, Inc. (NASDAQ: SGMO), a genomic medicine
company, and Pfizer, Inc. (NYSE: PFE) today announced updated
results from the Phase 1/2 Alta study evaluating investigational
SB-525 gene therapy for severe hemophilia A. The data showed that
SB-525 was generally well-tolerated and demonstrated a
dose-dependent increase in Factor VIII (FVIII) activity levels. The
first two patients treated at the 3e13 vg/kg dose rapidly achieved
normal levels of FVIII activity as measured using a chromogenic
assay, with no reported bleeding events, and the response continues
to be durable for as long as 24 weeks, the extent of follow-up. The
two patients more recently treated at the 3e13 vg/kg dose level are
demonstrating FVIII activity kinetics that appear consistent with
the first two patients treated in this dose cohort at similar early
time points. Data from 10 patients treated with SB-525 were
presented during an oral presentation on July 6 at the XXVII
Congress of the International Society on Thrombosis and Haemostasis
(ISTH), in Melbourne, Australia. The SB-525 ISTH presentation
slides, which include the full data set, are available on Sangamo’s
website in the Investors and Media section under Events and
Presentations.
This press release features multimedia. View
the full release here:
https://www.businesswire.com/news/home/20190705005294/en/
“The initial results with SB-525 gene therapy for patients with
severe hemophilia A continue to look very promising,” said Barbara
Konkle, M.D., Bloodworks Northwest, Professor of Medicine at
University of Washington and a Principal Investigator of the Alta
study. “It is encouraging that patients in the 3e13 vg/kg cohort
have attained normal Factor VIII levels within 5-7 weeks of
treatment with SB-525 gene therapy and have sustained Factor VIII
activity with no bleeding episodes. It will be important to
continue to follow these patients to understand the potential
long-term durability of this gene therapy.”
Alta study data presented at ISTH included 10 patients treated
across four ascending dose cohorts: 9e11 vg/kg (2 patients), 2e12
vg/kg (2 patients), 1e13 vg/kg (2 patients) and 3e13 vg/kg (4
patients). Factor VIII activity data presented at ISTH included
results through June 18, 2019. All other data presented at ISTH
were as of May 30, 2019.
Across the dose cohorts, patients demonstrated a dose-dependent
increase in FVIII levels and a dose-dependent reduction in the use
of FVIII replacement therapy. In the two patients treated with the
1e13 vg/kg dose, FVIII activity levels have been durable through
weeks 52 and 32. For the four patients in the 3e13 vg/kg cohort,
FVIII activity data were available through 24, 19, 6, and 4 weeks
of follow-up, respectively. The first two patients treated in the
3e13 vg/kg cohort (Patients 7 and 8) remained in the normal range,
as measured using a chromogenic assay, through 24 and 19 weeks of
follow-up, respectively. The next two patients in the 3e13 vg/kg
cohort (Patients 9 and 10), with 6 and 4 weeks of follow-up,
respectively, demonstrated rapid FVIII activity kinetics that
appear consistent with Patients 7 and 8 at similar early time
points. Also noted in the presentation at ISTH, Patient 9 attained
normal FVIII activity levels at week 7, subsequent to the data
transfer for the conference. No patient in the 3e13 vg/kg dose
cohort has experienced bleeding events as of the data cut-off date,
nor have patients in this dose cohort required factor replacement
following initial use of prophylactic factor.
SB-525 was generally well tolerated. Patients in the Alta study
were not treated with prophylactic steroids. One treatment-related
serious adverse event (SAE) was reported. This patient experienced
hypotension and fever six hours after completion of SB-525
infusion; this fully resolved with treatment and the patient was
discharged as planned within 24 hours. No similar hypotension event
was observed in the three subsequent patients dosed. Adverse events
observed in 10% (n=1) or more patients included: increased alanine
aminotransferase (30%) and aspartate aminotransferase (10%),
pyrexia (30%), fatigue (10%), hypotension (10%), myalgia (10%), and
tachycardia (10%). No patients treated with SB-525 have experienced
an alanine aminotransferase (ALT) elevation associated with a loss
of Factor VIII expression. In the 3e13 vg/kg cohort, two subjects
experienced a transient grade 1 ALT elevation (>1.5 x baseline)
managed with a tapering course of oral steroids.
“The initial results of the Alta study presented at ISTH
demonstrate that SB-525 has the potential to be a predictable and
reliable treatment that may bring clinical benefit to patients with
hemophilia A,” said Adrian Woolfson, M.D., Ph.D., Executive Vice
President of Research and Development, Sangamo. “The results show
that SB-525 is well tolerated, that Factor VIII levels in the first
two patients in the 3e13 vg/kg cohort reached normal, sustained
levels as measured using a chromogenic assay, and that variability
of Factor VIII activity is low, both within each patient and within
each dose cohort. We look forward to continuing to follow these
patients to further understand the durability of response to SB-525
gene therapy and to working with Pfizer to potentially advance a
registrational study.”
Based on the accumulating results from the Alta study, the U.S.
Food and Drug Administration (FDA) has granted regenerative
medicine advanced therapy (RMAT) designation for SB-525 gene
therapy to treat severe hemophilia A. RMAT designation is granted
to regenerative medicine therapies intended to treat, modify,
reverse, or cure a serious condition, for which preliminary
clinical evidence indicates that the medicine has the potential to
address an unmet medical need. The RMAT designation includes all
the benefits of the fast track and breakthrough therapy designation
programs, including early interactions with FDA.
“We are encouraged by the initial clinical data suggesting
safety, tolerability, and efficacy of SB-525 and are beginning
preparations, including manufacturing, to potentially advance into
a registrational study. We are also encouraged by our interactions
with regulators and by the FDA’s recent RMAT designation,” said
Seng Cheng, Senior Vice President and Chief Scientific Officer of
Pfizer’s Rare Diseases Research Unit. “If FVIII levels are
sustained, and patients continue to have no bleeding episodes and
remain off factor replacement therapy, we believe that this gene
therapy may potentially represent a transformative treatment
paradigm for severe hemophilia A.”
The fifth patient in the 3e13 vg/kg cohort (Patient 11) is
expected to be treated soon. Sangamo and Pfizer are working on
plans to advance SB-525 to a registrational study. Pfizer will
assume responsibility for SB-525 late-stage development and
manufacturing. Transfer of the SB-525 manufacturing process from
Sangamo to Pfizer has been initiated.
In addition to the collaboration for the development and
commercialization of gene therapies for hemophilia A, Sangamo and
Pfizer are also working together on the development of gene
therapies for amyotrophic lateral sclerosis (ALS) and
frontotemporal lobar degeneration (FTLD) using Sangamo’s
proprietary zinc finger protein transcription-factor technology
(ZFP-TF).
About the Alta study
The Phase 1/2 Alta study is an open-label, dose-ranging clinical
trial designed to assess the safety and tolerability of SB-525 in
patients with severe hemophilia A. The mean age of the ten patients
assessed is 31 years (range 18-47 years). All ten patients are
male. The U.S. Food and Drug Administration has granted Orphan
Drug, Fast Track, and regenerative medicine advanced therapy (RMAT)
designations to SB-525, which also received Orphan Medicinal
Product designation from the European Medicines Agency. SB-525 is
being developed as part of a global collaboration between Sangamo
and Pfizer.
About SB-525 Gene Therapy
SB-525 comprises a recombinant adeno-associated virus serotype 6
vector (AAV6) encoding the complementary deoxyribonucleic acid for
B domain deleted human FVIII. The SB-525 vector cassette was
designed to optimize both the vector manufacturing yield and
liver-specific FVIII protein expression. The SB-525 transcriptional
cassette incorporates multi-factorial modifications to the
liver-specific promoter module, FVIII transgene, synthetic
polyadenylation signal and vector backbone sequence.
About Sangamo Therapeutics
Sangamo Therapeutics, Inc. is focused on translating
ground-breaking science into genomic medicines with the potential
to transform patients' lives. Our capabilities in gene therapy,
cell therapy, genome editing, and gene regulation allow us to apply
the appropriate therapeutic approach to the underlying genetic
cause of the disease. For more information about Sangamo, visit
www.sangamo.com.
Pfizer Inc: Working together for a healthier world®
At Pfizer, we apply science and our global resources to bring
therapies to people that extend and significantly improve their
lives. We strive to set the standard for quality, safety and value
in the discovery, development and manufacture of health care
products. Our global portfolio includes medicines and vaccines as
well as many of the world’s best-known consumer health care
products. Every day, Pfizer colleagues work across developed and
emerging markets to advance wellness, prevention, treatments and
cures that challenge the most feared diseases of our time.
Consistent with our responsibility as one of the world’s premier
innovative biopharmaceutical companies, we collaborate with health
care providers, governments and local communities to support and
expand access to reliable, affordable health care around the world.
For more than 150 years, we have worked to make a difference for
all who rely on us. We routinely post information that may be
important to investors on our website at www.pfizer.com. In
addition, to learn more, please visit us on www.pfizer.com and
follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube
and like us on Facebook at Facebook.com/Pfizer.
Pfizer Disclosure Notice
The information contained in
this release is as of July 5, 2019. Pfizer assumes no obligation to
update forward-looking statements contained in this release as the
result of new information or future events or
developments.
This release contains
forward-looking information about an investigational hemophilia A
agent, SB-525, including its potential benefits, that involves
substantial risks and uncertainties that could cause actual results
to differ materially from those expressed or implied by such
statements. Risks and uncertainties include, among other things,
the uncertainties inherent in research and development, including
the ability to meet anticipated clinical endpoints, commencement
and/or completion dates for our clinical trials, regulatory
submission dates, regulatory approval dates and/or launch dates, as
well as the possibility of unfavorable new clinical data and
further analyses of existing clinical data; risks associated with
interim data; the risk that clinical trial data are subject to
differing interpretations and assessments by regulatory
authorities; whether regulatory authorities will be satisfied with
the design of and results from our clinical studies; whether and
when drug applications for any potential indications for SB-525 may
be filed in any jurisdictions; whether and when regulatory
authorities in any jurisdictions may approve any such applications,
which will depend on myriad factors, including making a
determination as to whether the product's benefits outweigh its
known risks and determination of the product's efficacy and, if
approved, whether SB-525 will be commercially successful; decisions
by regulatory authorities impacting labeling, manufacturing
processes, safety and/or other matters that could affect the
availability or commercial potential of SB-525; and competitive
developments.
A further description of risks
and uncertainties can be found in Pfizer's Annual Report on Form
10-K for the fiscal year ended December 31, 2018 and in its
subsequent reports on Form 10-Q, including in the sections thereof
captioned "Risk Factors" and "Forward-Looking Information and
Factors That May Affect Future Results", as well as in its
subsequent reports on Form 8-K, all of which are filed with the
U.S. Securities and Exchange Commission and available at
www.sec.gov and www.pfizer.com.
Sangamo Disclosure Notice
This press release contains
forward-looking statements based on Sangamo's current expectations.
These forward-looking statements include, without limitation,
statements relating to the investigational hemophilia A gene
therapy, SB-525, including its potential therapeutic benefits; the
potential long-term durability of SB-525 gene therapy; SB-525
having the potential to be a predictable and reliable treatment
that may bring clinical benefit to patients with hemophilia A and
to potentially represent a transformative treatment paradigm; plans
to advance SB-525 into a potential registrational study; the
potential benefits of the RMAT designation for SB-525; and other
statements that are not historical fact. These statements are not
guarantees of future performance and are subject to certain risks,
uncertainties and assumptions that are difficult to predict.
Factors that could cause actual results to differ include, but are
not limited to, risks and uncertainties related to: the costly and
inherently uncertain research and development process; preliminary
or initial data, including the risk that the initial data reported
from the Alta study to date may not be indicative of the final
results from the Alta study and that such final results may not
validate and support the safety and efficacy of SB-525; the
completion of the Alta study; the possibility of unfavorable new
clinical data from the Alta study and further analyses of existing
clinical data from the study that may material change clinical
outcomes; the risk that clinical trial data are subject to
differing interpretations and assessments by regulatory
authorities; whether regulatory authorities will be satisfied with
the design of and results from the Alta study, any potential
registrational studies or any other clinical studies of SB-525;
Sangamo’s limited experience in conducting later stage clinical
trials and the potential inability of Pfizer and Sangamo to advance
SB-525 into a registrational study; whether Sangamo will be able to
maintain or receive the benefits associated with RMAT, Orphan Drug,
Fast Track and Orphan Medicinal Product designations for SB-525;
the fact that RMAT, Orphan Drug, Fast Track and Orphan Medicinal
Product designations may not lead to a faster development,
regulatory review or approval process, and do not increase the
likelihood that SB-525 will receive any marketing approvals;
Sangamo's reliance on Pfizer and other third-parties to meet their
clinical and manufacturing obligations; Sangamo’s ability to
maintain strategic partnerships; and the potential for
technological developments by Sangamo's competitors that will
obviate Sangamo's gene therapy technology. Further, there can be no
assurance that the necessary regulatory approvals will be obtained
for SB-525 or that Sangamo and its partners will be able to develop
commercially viable product candidates. Actual results may differ
from those projected in forward-looking statements due to these and
other risks and uncertainties that exist in Sangamo's operations
and business environments. These risks and uncertainties are
described more fully in Sangamo's Quarterly Report on Form 10-Q for
the quarter ended March 31, 2019 as filed with the Securities and
Exchange Commission. Forward-looking statements contained in this
press release are made as of this date, and Sangamo undertakes no
duty to update such information except as required under applicable
law.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20190705005294/en/
Investor Relations – United States
McDavid Stilwell 510-970-6000, x219 mstilwell@sangamo.com
Media Inquiries – United States
Aron Feingold 510-970-6000, x421 afeingold@sangamo.com
Investor Relations and Media Inquiries –
European Union Caroline Courme 33 4 97 21 27 27
ccourme@sangamo.com
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