Hemophilia A is a rare bleeding disorder caused by mutations in the F8 gene, resulting in a deficiency of clotting factor VIII (FVIII), a protein that is required for normal blood clotting. The severity of hemophilia is determined by the amount of FVIII in the blood. The lower the amount of FVIII, the more likely it is that bleeding will occur, which can lead to serious health problems.
Hemophilia A occurs in approximately one in every 5,000-10,000 male births worldwide. For people who live with hemophilia A, there is an increased risk of spontaneous bleeding as well as bleeding following injuries or surgery. It is a lifelong disease that requires constant monitoring and therapy.
Giroctocogene fitelparvovec is a liver-tropic rAAV6 vector carrying a B-domain deleted F8 gene that is delivered through a single IV infusion. Giroctocogene fitelparvovec aims to deliver a working copy of the F8 gene to the liver so that liver cells can start producing functional FVIII clotting factor.
The Phase 1/2 Alta study is a single-dose, open-label, dose-ranging, multicenter, global clinical trial designed to assess the safety and tolerability of giroctocogene fitelparvovec in patients with severe hemophilia A. The mean age of the 11 male patients assessed across four dose cohorts (9e11 vg/kg – 2 patients; 2e12 vg/kg – 2 patients; 1 e13 vg/kg – 2 patients; and 3e13 vg/kg – 5 patients) is 30 years (range 18-47 years). Patients in this study will be assessed every six months until they enroll in a long-term follow-up study.
The Phase 3 AFFINE (NCT04370054) study is an open-label, single-dose, single-arm, multicenter study to evaluate the efficacy and safety of a single infusion of giroctocogene fitelparvovec in more than 60 adult (ages 18-64 years) male participants with moderately severe to severe hemophilia A. Eligible study participants will have completed at least six months of routine FVIII prophylaxis therapy during the lead-in Phase 3 study (NCT03587116) in order to collect pretreatment data for efficacy and selected safety parameters.
The primary endpoint is impact on annualized bleeding rate (ABR) through 12 months following treatment with giroctocogene fitelparvovec. This will be compared to ABR on prior FVIII prophylaxis replacement therapy. The secondary endpoints include FVIII activity level after the onset of steady state and through 12 months following infusion of giroctocogene fitelparvovec.
Giroctocogene fitelparvovec has received Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations from the U.S. Food and Drug Administration (FDA) and Orphan Medicinal Product designation from the European Medicines Agency (EMA).