Sangamo’s gene therapy holds promise in treating hemophilia APublished: July 10, 2019
Sangamo Therapeutics together with its collaborator Pfizer has an¬nounced encouraging interim re¬sults from its ongoing Phase 1/2 study evaluating an AAV-based gene therapy approach to treat severe he¬mophilia A.
Data presented at the XXVII Congress of the International Society on Thrombosis and Haemostasis (ISTH), in Melbourne, Australia reported encouraging results of Sangamo’s Phase 1/2 Alta gene therapy trial.
The Alta study of SB-525 is de¬signed to evaluate the safety and kinetics of a single intravenous in¬fusion of SB-525 in hemophilia A patients. SB-525 is a recombinant adeno-associated virus vector 6 (AAV6) encoding the complemen¬tary deoxyribonucleic acid for B do¬main deleted human FVIII.
The study evaluated ten pa¬tients across four ascending dosage cohorts; two patients in the first three cohorts and 4 patients in the highest dose (3e13 vg/kg) cohort. Patients demonstrated a dose-dependent increase in FVIII levels and dose-dependent decrease in the use of FVIII replacement therapy. Patients in the highest dose cohort achieved normal FVIII levels starting at 5-7 weeks following the therapy. The treatment was generally well tolerated.
2 patients in the 3e13 vg/kg cohort continue to have normal FVIII levels through 24 and 19 weeks of follow-up. The next two patients in this cohort are at 7 and 4 weeks of follow-up and have demonstrated FVIII activity kinetics similar to that of the previous patients in the same cohort.
Sangamo entered into a global collaboration and license agree¬ment with Pfizer in 2017 for the SB-525 program. Later the col¬laboration was also extended to developing gene therapies for amyotrophic lateral sclerosis and frontotemporal lobar degeneration using Sangamo’s proprietary zinc finger protein transcription-factor technology.
SB-525 received FDA’s Orphan Drug and Fast Track designations and EMA’s Orphan Medicinal Product designation. FDA has also recently granted regenerative medicine advanced therapy (RMAT) designation for SB-525 gene therapy to treat severe hemophilia A. RMAT designation will allow the company to interact with FDA more frequently.
Sangamo intends to dose a fifth patient in the 3e13 vg/kg cohort. Sangamo and Pfizer are working on plans to advance SB-525 to a registrational study. Pfizer will hold responsibility for late-stage development and manufacturing of the therapy, transfer of which from Sangamo to Pfizer has been initiated.
Seng Cheng, Senior Vice President and Chief Scientific Officer of Pfizer’s Rare Diseases Research Unit commented: “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. 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.”
Source: Sangamo and Pfizer Announce Updated Phase 1/2 Results for SB-525 Investigational Hemophilia A Gene Therapy Showing Sustained Increased Factor VIII Levels; Press Release