Pfizer Inc. and Sangamo Therapeutics, Inc., a genomic medicines company, today announced updated follow-up data from the Phase 1/2 Alta study of giroctocogene fitelparvovec (SB-525or PF-07055480), an investigational gene therapy for patients with severe hemophilia A. These data are being presented today at the 62nd American Society for Hematology Annual meeting taking place virtually from December 5th - 8th. The oral presentation slides, which include follow-up data up to 85 weeks for the longest treated patient, are available on Sangamo’s website in the Investors and Media section under.

All five patients in the high dose 3 x 10 vg/kg cohort have had at least one year of follow-up and showed sustained factor VIII (FVIII) activity levels, with a group median FVIII activity of 56.9% and a group geometric mean FVIII activity of 70.4% via chromogenic assay from week 9 to 52. Steady-state FVIII activity was achieved for all patients in the 3 x 10 vg/kg cohort within 9 weeks of treatment with giroctocogene fitelparvovec, with no bleeding events and no FVIII infusions (beyond 3 weeks post-infusion) within the first year. As of the cutoff date of August 31, 2020, one patient had one target joint bleed requiring FVIII therapy, occurring after week 52.

“It is promising to see how quickly all five patients in the 3 x 10 vg/kg cohort achieved steady-state FVIII activity levels, with no bleeding events and no factor usage within the first year and only one target joint bleed after 52 weeks,” said Andrew D. Leavitt, MD, Professor of Medicine, University of California, San Francisco, CA, and investigator of the Alta and AFFINE studies. “Our focus now is to confirm these exciting findings in the Phase 3 study, and to gather long-term data by following these patients and others in the Phase 3 study over a longer period of time.”

Giroctocogene fitelparvovec was generally well tolerated. As previously reported, one patient in the 3 x 10 vg/kg dose cohort had a treatment-related serious adverse event of hypotension (grade 3) and fever (grade 2), with symptoms of headache and tachycardia, which occurred six hours post-infusion with giroctocogene fitelparvovec, and which fully resolved within 24 hours. No other treatment-related serious adverse events were reported as of the cutoff date. Among the five patients in the 3 x 10 vg/kg dose cohort, four received corticosteroids for liver enzyme (alanine aminotransferase, ALT) elevations. Three patients had subsequent ALT elevations that responded to corticosteroids. All episodes of ALT elevations fully resolved with oral corticosteroids, and as of the cutoff date no participants were on corticosteroids and no corticosteroid use has been initiated after week 52.

“We continue to be encouraged by the findings from this Phase 1/2 study, which now include durable factor VIII expression through one year of follow-up, and we look forward to continuing to follow these patients,” said Seng Cheng, Senior Vice President and Chief Scientific Officer of Pfizer’s Rare Disease Research Unit. “With the first patient dosed in the Phase 3 AFFINE study in October 2020, we are on track for a readout from this pivotal Phase 3 trial in 2022, which will allow us to better assess the potential of our gene therapy across a larger sample size.”

“These latest results demonstrate that this gene therapy may bring clinical benefit to patients and has the potential to serve as an alternative to the burdensome standard of care for patients with hemophilia A,” said Bettina Cockroft, M.D., M.B.A, Chief Medical Officer of Sangamo. “We look forward to continuing to support our collaboration partners at Pfizer as they conduct the Phase 3 AFFINE study and assess the full potential of this promising therapy.”

Pfizer and Sangamo plan to present further follow-up data from the Alta study when all five patients in the 3 x 1013 vg/kg dose cohort have been followed for at least two years.