Sangamo and Pfizer Announce Updated Phase 1/2 Results for SB-525 Investigational Hemophilia A Gene Therapy Showing Sustained Increased Factor VIII Levels
- 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
FDArecently granted regenerative medicine advanced therapy (RMAT) designation for SB-525 gene therapy to treat severe hemophilia A
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“The initial results with SB-525 gene therapy for patients with severe hemophilia A continue to look very promising,” said
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
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
Based on the accumulating results from the Alta study, the
“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
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.
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.
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,
Pfizer Disclosure Notice
The information contained in this release is as of
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
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
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