Sangamo and Pfizer Announce Phase 1/2 Interim Data for Investigational Hemophilia A Gene Therapy
- 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
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.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190402005390/en/
“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.
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
View source version on businesswire.com: https://www.businesswire.com/news/home/20190402005390/en/