Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B

K.John Pasi; Kathelijn Fischer; Margaret Ragni; Beatrice Nolan; David J. Perry; Roshni Kulkarni; Margareth Ozelo; Johnny Mahlangu; Amy D. Shapiro; Ross I. Baker; Carolyn M. Bennett; Christopher Barnes; Johannes Oldenburg; Tadashi Matsushita; Huixing Yuan; Alejandra Ramirez-Santiago; Glenn F. Pierce; Geoffrey Allen; Baisong Mei

doi:10.1160/TH16-05-0398

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2017; 117(03): 508-518
DOI: 10.1160/TH16-05-0398

Coagulation and Fibrinolysis

Schattauer GmbH

Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B

Authors

K.John Pasi

¹Royal London Haemophilia Centre, Barts and The London School of Medicine and Dentistry, London, UK
Kathelijn Fischer

²Van Creveldkliniek, University Medical Center, Utrecht, The Netherlands
Margaret Ragni

³Hemophilia Center of Western Pennsylvania, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Beatrice Nolan

⁴Our Lady’s Children’s Hospital, Dublin, Ireland
David J. Perry

⁵Addenbrookes Hospital, Cambridge, UK
Roshni Kulkarni

⁶Michigan State University, East Lansing, Michigan, USA
Margareth Ozelo

⁷INCT do Sangue Hemocentro UNICAMP, University of Campinas, Brazil
Johnny Mahlangu

⁸Haemophilia Comprehensive Care Centre, Faculty of Health Sciences, University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital and NHLS, Johannesburg, South Africa
Amy D. Shapiro

⁹Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana, USA
Ross I. Baker

¹⁰Western Australian Centre for Thrombosis and Haemostasis, Murdoch University, Perth, Western Australia, Australia
Carolyn M. Bennett

¹¹Emory University School of Medicine, Children’s Healthcare of Atlanta, Aflac Cancer and Blood Disorders Center, Atlanta, Georgia, USA
Christopher Barnes

¹²The Royal Children’s Hospital, Parkville, Melbourne, Victoria, Australia
Johannes Oldenburg

¹³Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, Bonn, Germany
Tadashi Matsushita

¹⁴Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan
Huixing Yuan

¹⁵Biogen, Cambridge, Massachusetts, USA
Alejandra Ramirez-Santiago

¹⁵Biogen, Cambridge, Massachusetts, USA
Glenn F. Pierce

¹⁵Biogen, Cambridge, Massachusetts, USA
Geoffrey Allen

¹⁵Biogen, Cambridge, Massachusetts, USA
Baisong Mei

¹⁵Biogen, Cambridge, Massachusetts, USA

Abstract

Summary

The safety, efficacy, and prolonged half-life of recombinant factor IX Fc fusion protein (rFIXFc) were demonstrated in the Phase 3 B-LONG (adults/adolescents ≥12 years) and Kids B-LONG (children <12 years) studies of subjects with haemophilia B (≤2 IU/dl). Here, we report interim, long-term safety and efficacy data from B-YOND, the rFIXFc extension study. Eligible subjects who completed B-LONG or Kids B-LONG could enrol in B-YOND. There were four treatment groups: weekly prophylaxis (20–100 IU/kg every 7 days), individualised prophylaxis (100 IU/kg every 8–16 days), modified prophylaxis (further dosing personalisation to optimise prophylaxis), and episodic (ondemand) treatment. Subjects could change treatment groups at any point. Primary endpoint was inhibitor development. One hundred sixteen subjects enrolled in B-YOND. From the start of the parent studies to the B-YOND interim data cut, median duration of rFIXFc treatment was 39.5 months and 21.9 months among adults/adolescents and children, respectively; 68/93 (73.1 %) adults/adolescents and 9/23 (39.1 %) children had ≥100 cumulative rFIXFc exposure days. No inhibitors were observed. Median annualised bleeding rates (ABRs) were low in all prophylaxis regimens: weekly (≥12 years: 2.3; <6 years: 0.0; 6 to <12 years: 2.7), individualised (≥12 years: 2.3; 6 to <12 years: 2.4), and modified (≥12 years: 2.4). One or two infusions were sufficient to control 97 % (adults/adolescents) and 95 % (children) of bleeding episodes. Interim data from B-YOND are consistent with data from B-LONG and Kids B-LONG, and confirm the longterm safety of rFIXFc, absence of inhibitors, and maintenance of low ABRs with prophylactic dosing every 1 to 2 weeks.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Factor IX - haemophilia - prophylaxis - recombinant fusion proteins

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Referenzen

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