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Haemophilia. 2017 Mar;23(2):238-246. doi: 10.1111/hae.13119. Epub 2016 Nov 27.

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

Author information

1
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
2
SI Institute of Blood Pathology and Transfusion Medicine of NAMSU, Lviv, Ukraine.
3
Hospital Universitario La Paz, Madrid, Spain.
4
Hospital Tengku Ampuan Rahimah, Klang, Selangor, Malaysia.
5
Great Ormond Street Hospital for Children, London, UK.
6
Baxalta Innovations GmbH, now part of Shire, Vienna, Austria.

Abstract

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.

KEYWORDS:

children; extended half-life FVIII; prophylaxis

PMID:
27891721
DOI:
10.1111/hae.13119
[Indexed for MEDLINE]

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