Pfizer, Sangamo’s gene therapy show promise in phase 1/2 hemophilia A study

Pfizer and Sangamo Therapeutics revealed updated results from the Phase 1/2 Alta study, which demonstrated that SB-525 was generally well-tolerated and showed a dose-dependent increase in Factor VIII (FVIII) activity levels.

The SB-525 already secured orphan drug, fast track, and regenerative medicine advanced therapy (RMAT) designations from the US Food and Drug Administration, as well as orphan medicinal product designation from the European Medicines Agency.

The SB-525 includes a recombinant adeno-associated virus serotype 6 vector (AAV6), which encodes the complementary deoxyribonucleic acid for B domain deleted human FVIII. Its transcriptional cassette integrates multi-factorial modifications to the liver-specific promoter module, FVIII transgene, synthetic polyadenylation signal and vector backbone sequence.

Alta study principal investigator Dr Bloodworks said: “The initial results with SB-525 gene therapy for patients with severe hemophilia A continue to look very promising.”

The patients showed a dose-dependent increase in FVIII levels and a dose-dependent reduction in the use of FVIII replacement therapy across the dose cohorts.

The phase 1/2 Alta trial is an open-label and dose-ranging clinical study designed to evaluate the safety and tolerability of SB-525 in patients with severe hemophilia A.

Both firms are planning to advance SB-525 to a registrational study, and Pfizer will take responsibility for SB-525 late-stage development and manufacturing. A process has been initiated to transfer SB-525 manufacturing process from Sangamo to Pfizer.

The US Food and Drug Administration (FDA) has granted regenerative medicine advanced therapy (RMAT) designation for SB-525 gene therapy to treat severe hemophilia A, based on the accumulating results from the Alta study.

Sangamo and Pfizer have also collaborated 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), in addition to the development and commercialisation of gene therapies for hemophilia A.

Pfizer’s rare diseases research unit chief scientific officer and senior vice president Seng Cheng said: “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.”