Recombinant B-domain-deleted porcine sequence factor VIII (r-pFVIII) for the treatment of bleeding in patients with congenital haemophilia A and inhibitors

Abstract

Introduction: 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.