Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A.

INTRODUCTION

Primary factor VIII (FVIII) prophylaxis is the optimal treatment in children with severe haemophilia A. They are expected to benefit from extended half-life (T ) FVIII coverage by reduced infusion frequency while maintaining haemostatic efficacy.

AIMS

To determine immunogenicity, pharmacokinetics (PK), efficacy, safety and quality of life of prophylaxis with a polyethylene glycol (peg)-ylated FVIII (BAX 855) based on full-length recombinant FVIII (ADVATE) in paediatric previously treated patients (PTPs) with severe haemophilia A.

METHODS

PTPs <12 years without history of FVIII inhibitors received twice-weekly infusions of 50 ± 10 IU kg BAX 855 for ≥50 exposure days. Prophylactic dose increases to ≤80 IU kg were allowed under predefined conditions. PK was evaluated after single infusions of 60 ± 5 IU kg .

RESULTS

T and mean residence time were extended 1.3- to 1.5-fold compared to ADVATE (n = 31), depending on the analysis used. The point estimate for the mean annualized bleeding rate in 66 subjects receiving a median of 1.9 weekly infusions of 51.3 IU kg of BAX 855 each was 3.04 (median 2.0); 1.10 (median 0) for joint and 1.16 (median 0) for spontaneous bleeds. Overall, 38% of subjects had zero bleeds. No bleeds were severe. Haemostatic efficacy was rated excellent or good for 90% of bleeds; 91% were treated with one or two infusions. In 8/14 subjects all target joints resolved. No subject developed FVIII inhibitors or persistent binding antibodies that affected safety or efficacy. No adverse reactions occurred.

CONCLUSION

Twice-weekly prophylaxis with BAX 855 was safe and efficacious in paediatric PTPs with severe haemophilia A.