Updated Giroctocogene Fitelparvovec Study for Patients with Severe Hemophilia A

Pfizer Inc and Sangamo Therapeutics Inc announced follow-up data from the phase 1 and phase 2 Alta study of giroctocogene fitelparvovec (SB-525 or PF-07055480), an investigational gene therapy for patients with severe hemophilia A, which was presented at the 62^nd American Society of Hematology Annual meeting on December 7, 2020.

The update outlines that all 5 patients in the high dose 3 x 10¹³ vg/kg cohort have had at least 1 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 10¹³ vg/kg cohort within 9 weeks of treatment with giroctocogene fitelparvovec, with no bleeding events and no FVIII infusions during the first year, according to the study authors.

As of the cutoff date on August 31, 2020, 1 patient had a target joint bleed requiring FVIII therapy, occurring after week 52.

“It is promising to see how quickly all five patients in the 3 x 1013 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 Alta and AFFINE study investigator Andrew D. Leavitt, MD, in a press release. “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, with 1 patient in the 3 x 1013 vg/kg dose cohort reporting a treatment-related serious adverse event (TRAE) of hypotension and fever, with symptoms of headache and tachycardia, which occurred 6 hours post-infusion with giroctocogene fitelparvovec, and which fully resolved within 24 hours. No other TRAEs were reported as of the cutoff date.

Among the 5 patients in the 3 x 1013 vg/kg dose cohort, 4 received corticosteroids for liver enzyme (alanine aminotransferase or ALT) elevations. Further, 3 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.

“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, MD, MBA, chief medical officer of Sangamo, in a press release. “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.”

REFERENCE

Pfizer and Sangamo Announce Updated Phase 1/2 Results Showing Sustained Factor VIII Activity Levels in 3x1013 VG/KG Cohort Through One Year Following Hemophilia A Gene Therapy. BusinessWire. https://www.businesswire.com/news/home/20201207005251/en/Pfizer-and-Sangamo-Announce-Updated-Phase-12-Results-Showing-Sustained-Factor-VIII-Activity-Levels-in-3x1013-VGKG-Cohort-Through-One-Year-Following-Hemophilia-A-Gene-Therapy. Published December 7, 2020. Accessed December 8, 2020.