Objective:
This report assesses the changes in bleeding patterns as previously treated severe hemophilia A patients were switched from their pre-study standard factor VIII (FVIII) prophylactic treatment regimen to prophylaxis with BAX 855 - an extended half-life, pegylated, full-length recombinant FVIII built on ADVATE - during their participation in the pivotal trial.
Methods:
Patients’ informed consent and appropriate ethics committee approvals were obtained. At baseline, eligible patients reported their pre-study treatment regimen and average annualized bleeding rate (ABR) for the previous 3-6 months. Patients assigned to the prophylactic arm were to receive 45±5 IU/kg of BAX 855 twice weekly for ≥50 exposure days or approximately 6 months. This per-protocol analysis included 101 treated patients in the prophylactic arm.
Summary:
The overall mean (SD) ABR for these treated patients was 3.7 (4.7), which was lower than the ABR for the 17 patients treated on-demand during the study (40.8 [16.3] - who were all treated on-demand pre-study). Of the 101 subjects in BAX 855 prophylactic arm, 82 were treated on prophylaxis and 19 were treated on-demand during the pre-study period. The BAX 855 prophylactic dosing frequency was reduced by a mean (SD) of 26.7% (27.9) compared to the frequency reported in the pre-study period, which is approximately equivalent to one less prophylactic infusion per week when using BAX 855 for prophylaxis. The mean dose per prophylactic infusion was higher for the BAX 855 treatment regimen compared to pre-study (44.53 vs 38.12 IU/kg), but FVIII consumption per week was lower during the study compared to pre-study (83.96 vs 97.79 IU/kg/week). More patients treated on BAX 855 prophylaxis during the study treatment period had zero bleeding episodes compared to during their pre-study period: 37.8% vs 23.2%. The mean ABR was lower for subjects on BAX 855 prophylaxis compared to pre-study: 4.13 vs 9.74.
As expected, the 19 patients treated on-demand pre-study had a higher mean ABR (31.53) and all experienced bleeding (ie, none had zero hemarthroses during the pre-study period) compared to during their BAX 855 prophylactic treatment period (mean ABR of 1.68 and 47.4% had zero bleeding episodes).
Conclusions:
These results further demonstrate the benefit of BAX 855 prophylaxis (45±5 IU/kg twice weekly) and support its efficacy profile for the prevention of bleeding when used twice weekly, which suggests that fewer infusions may be needed to maintain prophylactic efficacy.