Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Real Life: One-Year Clinical and Economic Outcomes

Objective: To evaluate the efficacy of recombinant factor VIII FC fusion protein in haemophilia A patientreceiving on demand treatment only. Study Design: Comparative cross sectional study. Place and Duration of Study: Department of Hematology, Armed Forces Institute of Pathology and PakistanHemophilia Welfare Society, Rawalpindi, from Jun to Dec 2017. Methodology: Eighty-nine male patients of Hemophilia A already receiving recombinant factor VIII (20-30 Units/kg) on demand, with no history of inhibitors were included in study. Patients were divided as per age into paediatric and adult group and also on the basis of their basal factor VIII levels into severe, moderate and mild groups. Same patients were switched to recombinant factor VIII FC fusion protein (20-30 Units/kg) and its efficacy was measured and compared with recombinant Factor VIII in terms of dose requirement, injections, bleeds in six month period, presence of inhibitors and side effects. Results: Eighty nine male patients were studied. There was significant reduction in dose from median value of5750 units for group I to 4000 units for group II. Number of bleed in six month period were reduced from 5.3 ingroup I to 4.5 in group II. Number of injections were reduced on average to 1-2 injection per bleed in group II. No inhibitors were detected in group II. Conclusion: rFVIII Fc fusion protein has prolong activity and results in reduction of total dose, number of bleed,dose per bleed and has reduced antigenecity.

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Faculty Opinions recommendation of Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.720026512.793527664 ◽

2017 ◽

Author(s):

Chava Kimchi-Sarfaty

Keyword(s):

Fusion Protein ◽

Factor Viii ◽

Hemophilia A ◽

Recombinant Factor Viii ◽

Fc Fusion Protein

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Faculty Opinions recommendation of Reduction of Factor VIII Inhibitor Titers During Immune Tolerance Induction With Recombinant Factor VIII-Fc Fusion Protein.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726061363.793544802 ◽

2018 ◽

Author(s):

Valder Arruda ◽

Ben Samelson-Jones

Keyword(s):

Fusion Protein ◽

Factor Viii ◽

Immune Tolerance ◽

Tolerance Induction ◽

Recombinant Factor Viii ◽

Factor Viii Inhibitor ◽

Immune Tolerance Induction ◽

Fc Fusion Protein ◽

Viii Inhibitor

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Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs

Blood ◽

10.1182/blood-2011-08-367813 ◽

2012 ◽

Vol 119 (13) ◽

pp. 3024-3030 ◽

Cited By ~ 99

Author(s):

Jennifer A. Dumont ◽

Tongyao Liu ◽

Susan C. Low ◽

Xin Zhang ◽

George Kamphaus ◽

...

Keyword(s):

Fusion Protein ◽

Factor Viii ◽

Half Life ◽

Hemophilia A ◽

Specific Activity ◽

Recombinant Factor Viii ◽

Prophylactic Efficacy ◽

Reduced Frequency ◽

Fc Fusion Protein ◽

Partial Correction

Abstract Despite proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of factor VIII. A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed to determine the potential for reduced frequency of dosing. rFVIIIFc has an ∼ 2-fold longer half-life than rFVIII in hemophilia A (HemA) mice and dogs. The extension of rFVIIIFc half-life requires interaction of Fc with the neonatal Fc receptor (FcRn). In FcRn knockout mice, the extension of rFVIIIFc half-life is abrogated, and is restored in human FcRn transgenic mice. The Fc fusion has no impact on FVIII-specific activity. rFVIIIFc has comparable acute efficacy as rFVIII in treating tail clip injury in HemA mice, and fully corrects whole blood clotting time (WBCT) in HemA dogs immediately after dosing. Furthermore, consistent with prolonged half-life, rFVIIIFc shows 2-fold longer prophylactic efficacy in protecting HemA mice from tail vein transection bleeding induced 24-48 hours after dosing. In HemA dogs, rFVIIIFc also sustains partial correction of WBCT 1.5- to 2-fold longer than rFVIII. rFVIIIFc was well tolerated in both species. Thus, the rescue of FVIII by Fc fusion to provide prolonged protection presents a novel pathway for FVIII catabolism, and warrants further investigation.

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