Sangamo, Pfizer announce Phase 1/2 interim data for SB-525 gene therapy

Sangamo Therapeutics (SGMO) and Pfizer (PFE) 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 levels across the four dosage cohorts. Eight patients total were dosed. Based on these results, the Safety Monitoring Committee recommended cohort expansion at the 3e13 vg/kg dose. The Phase 1/2 interim data include eight patients treated across four ascending dosage cohorts. 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. At week 6 post infusion, the two fourth dose cohort patients reached 140% and 94% of normal and 93% and 65%. 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 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. 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 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. The same patient in the fourth cohort experienced the aforementioned serious adverse event. SB-525 comprises a recombinant adeno-associated virus serotype 6 vector 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. 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.

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