J N Mahlangu1, T A Andreeva2, D E Macfarlane3, C Walsh4, N S Key5. 1. Department of Molecular Medicine and Haematology, Faculty of Health Sciences, Haemophilia Comprehensive Care Centre, NHLS and University of the Witwatersrand, Johannesburg, South Africa. 2. City Haemophilia Center, Saint Petersburg, Russia. 3. Department of Internal Medicine, University of Iowa, Iowa City, IA, USA. 4. Mt Sinai School of Medicine, New York, NY, USA. 5. Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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.
INTRODUCTION: Development of inhibitors to humanFVIII (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.
Authors: Claude Négrier; Johannes Oldenburg; Gili Kenet; Shannon L Meeks; Jean-Claude Bordet; Jens Müller; Sandra Le Quellec; Peter L Turecek; Nikola Tripkovic; Yesim Dargaud Journal: Res Pract Thromb Haemost Date: 2022-06-19