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Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia
E S Mullins1, O Stasyshyn2, M T Alvarez-Román3
1Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Insights
Twice-weekly prophylaxis with BAX 855 demonstrated safety and efficacy in children with severe hemophilia A. This extended half-life factor VIII (FVIII) treatment reduced bleeding events and improved outcomes in previously treated patients.
Area of Science:
- Hematology
- Pharmacology
- Pediatrics
Background:
- Severe hemophilia A in children necessitates effective factor VIII (FVIII) prophylaxis.
- Extended half-life (T1/2) FVIII formulations aim to reduce infusion frequency while maintaining efficacy.
Purpose of the Study:
- To evaluate the immunogenicity, pharmacokinetics (PK), efficacy, safety, and quality of life associated with BAX 855 prophylaxis in pediatric patients with severe hemophilia A.
- BAX 855 is a novel polyethylene glycol (peg)-ylated FVIII concentrate based on full-length recombinant FVIII (ADVATE).
Main Methods:
- Paediatric previously treated patients (PTPs) under 12 years old received twice-weekly BAX 855 infusions (50 ± 10 IU/kg) for at least 50 exposure days.
- Pharmacokinetic parameters were assessed after single infusions (60 ± 5 IU/kg).
- Dose adjustments up to 80 IU/kg were permitted under specific conditions.
Main Results:
- BAX 855 demonstrated a 1.3- to 1.5-fold increase in T1/2 and mean residence time compared to ADVATE.
- The mean annualized bleeding rate was 3.04 (median 2.0), with 38% of subjects experiencing zero bleeds.
- Excellent or good hemostatic efficacy was observed in 90% of bleeds, with no inhibitors or safety-affecting antibodies developing.
Conclusions:
- Twice-weekly prophylaxis with BAX 855 is safe and effective for pediatric PTPs with severe hemophilia A.
- BAX 855 offers a promising treatment option with reduced bleeding and improved outcomes.
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 (T1/2 ) 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-1 BAX 855 for ≥50 exposure days. Prophylactic dose increases to ≤80 IU kg-1 were allowed under predefined conditions. PK was evaluated after single infusions of 60 ± 5 IU kg-1 .
Results:
T1/2 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-1 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.
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