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Recombinant B‐domain‐deleted porcine sequence factor VIII (r‐ pFVIII ) for the treatment of bleeding in patients with congenital haemophilia A and inhibitors
Author(s) -
Mahlangu J. N.,
Andreeva T. A.,
Macfarlane D. E.,
Walsh C.,
Key N. S.
Publication year - 2017
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.13108
Subject(s) - medicine , recombinant dna , haemophilia a , sequence (biology) , haemophilia , haemophilia b , domain (mathematical analysis) , biochemistry , surgery , gene , biology , mathematical analysis , mathematics
Development of inhibitors to human FVIII ( hFVIII ) significantly complicates the control of bleeding events in patients with haemophilia A. Aim This prospective, multicentre, open‐label, non‐comparative, Phase II study evaluated the haemostatic activity of a recombinant B‐domain‐deleted porcine FVIII (r‐ pFVIII ), in the treatment of non‐life/non‐limb‐threatening bleeding in individuals with haemophilia A and FVIII inhibitors. Methods Acute bleeding episodes in patients with pFVIII inhibitor titres <0.8 BU mL −1 were treated with 50 U kg −1 body weight r‐ pFVIII . Those with pFVIII inhibitor titres of >0.8 BU mL −1 received an initial calculated r‐ pFVIII loading dose followed by 50 U kg −1 treatment dose. Treatment continued at 6‐hourly intervals until bleeding was determined, controlled or till a maximum of eight doses was reached. Results All 25 bleeding episodes in nine patients (mean age: 23.7 years; range: 14–34 years) were controlled successfully with eight or fewer injections of r‐ pFVIII . The median time from bleeding onset to the administration of r‐ pFVIII was 5.7 h (range: 1.5–20.0 h). Twenty of the bleeding episodes (80%) were controlled with one treatment dose of r‐ pFVIII (with or without a loading dose, median dose: 200.8 U kg −1 ; range: 50–576 U kg −1 ) regardless of pFVIII level. r‐ pFVIII was well tolerated and no treatment‐emergent serious adverse events were considered by the investigator to be related to r‐ pFVIII administration. Conclusion The results suggest that FVIII replacement therapy with r‐ pFVIII could be a viable alternative to bypassing agents for the treatment of bleeding episodes in individuals with haemophilia A and FVIII inhibitors.