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Thromb Haemost 2016; 116(01): 1-8
DOI: 10.1160/TH15-10-0780
Coagulation and Fibrinolysis
Schattauer GmbH

Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) for perioperative haemostatic management in severe haemophilia A

Johnny N. Mahlangu
1   Faculty of Health Sciences, University of the Witwatersrand and NHLS, Johannesburg, South Africa
,
Margaret Ragni
2   University of Pittsburgh and the Hemophilia Center of Western Pennsylvania, Pittsburgh, PA, USA
,
Naresh Gupta
3   Maulana Azad Medical College Associated LNJP Hospital, New Delhi, India
,
Savita Rangarajan
4   Basingstoke and North Hampshire Hospital, Basingstoke, UK
,
Robert Klamroth
5   Zentrum fuer Gefaessmedizin/Haemophiliezentrum, Vivantes Klinikum im Friedrichshain, Berlin, Germany
,
Johannes Oldenburg
6   University Clinic Bonn, Bonn, Germany
,
Keiji Nogami
7   Nara Medical University, Nara, Japan
,
Guy Young
8   Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California, USA
,
Lynda M. Cristiano
9   Biogen, Cambridge, Massachusetts, USA
,
Yingwen Dong
9   Biogen, Cambridge, Massachusetts, USA
,
Geoffrey Allen
9   Biogen, Cambridge, Massachusetts, USA
,
Glenn F. Pierce
9   Biogen, Cambridge, Massachusetts, USA
,
Brian Robinson
9   Biogen, Cambridge, Massachusetts, USA
› Author Affiliations Financial support: These studies were funded by Biogen and Sobi.
Further Information

Publication History

Received: 07 October 2015

Accepted after major revision: 28 February 2016

Publication Date:
27 November 2017 (online)

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Summary

The Phase 3 A-LONG and Kids A-LONG studies demonstrated the prolonged half-life of rFVIIIFc compared with rFVIII, and the safety and efficacy of rFVIIIFc in subjects with severe haemophilia A. Eligible subjects from A-LONG and Kids A-LONG continued rFVIIIFc treatment by enrolling in ASPIRE, an ongoing extension study. Based on combined data from the primary studies and ASPIRE interim data, the safety and efficacy of rFVIIIFc in subjects requiring surgery were evaluated. Perioperative dosing regimens were determined by investigators with guidance based on pharmacokinetic data and recommendations from a clinical dosing committee. In addition to dosing frequency, factor consumption, blood loss, transfusions, bleeding episodes, and haemostatic response were assessed. Across studies, 21 subjects underwent 23 evaluable major surgeries, including 19 orthopaedic surgeries; 41 subjects underwent 52 minor surgeries, including 30 dental procedures. No major and 10 minor surgeries were performed in paediatric subjects. Of the major (n = 22) and minor (n = 32) surgeries assessed for haemostatic response, all were rated as excellent or good by the investigator/surgeon. During most major surgeries (95.7 %), haemostasis was maintained with one rFVIIIFc infusion. Blood loss in major surgeries was consistent with similar surgeries in subjects without haemophilia. Across studies, rFVIIIFc was well tolerated; no subject developed an inhibitor.

Keywords

Phase 3 trial - factor VIII - haemophilia A - haemostasis - surgery

 

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