-
Eight patients treated with SB-525 gene therapy showed
dose-dependent increases in FVIII activity, with the two patients
treated with the 3e13 vg/kg dose reaching normal FVIII levels -
Safety Monitoring Committee recommended expansion of the 3e13 vg/kg
dose cohort
BRISBANE, Calif. & NEW YORK–(BUSINESS WIRE)–Sangamo Therapeutics, Inc. (NASDAQ: SGMO), a genomic medicine company,
and Pfizer, Inc. (NYSE: PFE) today announced interim data from the Phase
1/2 Alta study evaluating investigational SB-525 gene therapy for severe
hemophilia A. Data indicate that SB-525 was generally well-tolerated and
demonstrated a dose-dependent increase in Factor VIII (FVIII) levels
across the four dosage cohorts. Eight patients total were dosed. Based
on these results, the Safety Monitoring Committee (SMC) recommended
cohort expansion at the 3e13 vg/kg dose. Further details will be
disclosed during Sangamo’s conference call and webcast scheduled for
8:00 a.m. ET today, which can be accessed on the Sangamo website.
“The interim data from the first eight patients with hemophilia A
treated with SB-525 gene therapy in the Alta study are encouraging and
demonstrate a dose-dependent relationship, evidence of sustained factor
levels, and low variability, both within each patient and within each
cohort,” said Edward Conner, MD, Chief Medical Officer of Sangamo.
“These interim results suggest that SB-525 may be well-tolerated and may
prove to have the predictability and sustained treatment effect that can
bring clinical benefit in patients with hemophilia A. We need to
continue observing how the data mature and how additional patients in
the expansion cohort respond to SB-525. We look forward to working with
Pfizer to potentially advance SB-525 into a registrational study.”
The Phase 1/2 interim data include eight patients treated across four
ascending dosage cohorts (9e11 vg/kg, 2e12 vg/kg, 1e13 vg/kg and 3e13
vg/kg, with two patients per cohort). Patients demonstrated a
dose-dependent increase in FVIII levels, achieving clinically relevant
increases in FVIII activity in the higher dosage cohorts and normal
FVIII levels in the 3e13 vg/kg dose cohort (normal range: 50-150%). At
week 6 post infusion, the two fourth dose cohort patients reached 140%
and 94% of normal (as measured by one-stage clotting assay) and 93% and
65% (as measured by chromogenic assay). A dose-dependent reduction in
the use of Factor VIII replacement therapy was also observed, with
patients in the highest dose cohort not requiring factor replacement
therapy after initial use of prophylactic factor and experiencing no
bleeding events to date. SB-525 was generally well-tolerated, with one
patient (treated with the 3e13 vg/kg dose) reporting a treatment-related
serious adverse event of hypotension and fever, which occurred following
vector infusion and resolved with treatment within 24 hours of
completion of vector infusion.
“The interim results with SB-525 gene therapy for patients with severe
hemophilia A are early but very promising,” said Barbara Konkle, MD,
Bloodworks Northwest and Professor of Medicine at University of
Washington and investigator of the Alta study. “It will be important to
observe additional patients and for a longer follow-up duration to
determine whether these positive interim findings are recapitulated and
sustained.”
Patients in the Alta study were not treated with prophylactic steroids.
No treatment-related serious adverse events and no ALT elevations
requiring more than seven days of corticosteroid treatment were observed
in the first three cohorts. One patient in the fourth cohort experienced
an ALT elevation (>1.5x ULN) at week four that required a tapering
course of oral steroids. The patient did not have any associated loss of
Factor VIII activity or ALT elevations seven weeks following initiation
of the steroid therapy (five weeks post vector infusion). The same
patient in the fourth cohort experienced the aforementioned serious
adverse event.
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.
“We are encouraged by the early clinical data suggesting tolerability of
the recombinant AAV6 vector and potential for normalization of Factor
VIII levels. We look forward to the opportunity to expanding the cohort
administered a 3e13 vg/kg dose and subsequent planning for the pivotal
study,” said Seng Cheng, SVP and Chief Scientific Officer of Pfizer’s
Rare Diseases Research Unit. “As the development and commercial partner
for SB-525, we are encouraged by the possibility that SB-525 may one day
transform the treatment landscape for patients with hemophilia A.”
Longer-term follow-up data will be presented at an upcoming scientific
meeting. Per the SMC recommendation and study protocol, the fourth
cohort will be expanded by up to five patients. Patient enrollment is
underway.
In addition to the partnership for the development and commercialization
of gene therapies for hemophilia A, Sangamo and Pfizer are also
collaborating 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.
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 up to 20
adult patients with severe hemophilia A. The U.S. Food and Drug
Administration has granted Orphan Drug and Fast Track 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 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.
Forward-Looking Statements
Pfizer Disclosure Notice
The information contained in this release is as of April 2, 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 an investigational
hemophilia A gene therapy, SB-525, including its potential benefits,
plans for the ongoing development of SB-525 and plans to present
additional data, and plans to collaborate with Pfizer on other product
candidates, as well as 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
uncertainties inherent in research and development, including risks
associated with interim data; the possibility of unfavorable new
clinical data and further analyses of existing clinical 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 SB-525’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; competitive developments; and Sangamo’s reliance on partners
and other third-parties to further develop product candidates. These
risks and uncertainties and other risks are described more fully in
Sangamo’s Annual Report on Form 10-K for the year ended December 31,
2018 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.
Contacts
Investor Relations – United States
McDavid
Stilwell
510-970-6000, x219
mstilwell@sangamo.com
Varant Shirvanian
510-970-6000, x205
vshirvanian@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