K John Pasi1, Kathelijn Fischer2, Margaret Ragni3, Roshni Kulkarni4, Margareth C Ozelo5, Johnny Mahlangu6, Amy Shapiro7, Stephanie P'Ng8, Hervé Chambost9, Beatrice Nolan10, Carolyn Bennett11, Tadashi Matsushita12, Bent Winding13, Joachim Fruebis14, Huixing Yuan15, Dan Rudin14, Johannes Oldenburg16. 1. Royal London Haemophilia Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. 2. Van Creveldkliniek, University Medical Center, Utrecht, Netherlands. 3. Hemophilia Center of Western Pennsylvania, University of Pittsburgh, Pittsburgh, PA, USA. 4. Michigan State University, East Lansing, MI, USA. 5. Hemocentro UNICAMP, University of Campinas, Campinas, Brazil. 6. Haemophilia Comprehensive Care Centre, Faculty of Health Sciences, University of the Witwatersrand, and Charlotte Maxeke Johannesburg Academic Hospital and National Health Laboratory Service, Johannesburg, South Africa. 7. Indiana Hemophilia & Thrombosis Center, Inc., Indianapolis, IN, USA. 8. The Haemophilia and Haemostasis Centre, Fiona Stanley Hospital, Murdoch, WA, Australia. 9. Children's Hospital La Timone, and Aix Marseille University, INSERM, INRA, C2VN, Marseille, France. 10. Children's Health Ireland at Crumlin, Dublin, Ireland. 11. Emory University School of Medicine, Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, GA, USA. 12. Nagoya University Hospital, Nagoya, Japan. 13. Sobi, Stockholm, Sweden. 14. Bioverativ, a Sanofi company, Waltham, MA, USA. 15. Sanofi, Waltham, MA, USA. 16. Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
Abstract
INTRODUCTION: Recombinant factor IX Fc fusion protein (rFIXFc) has demonstrated efficacy for treatment of haemophilia B in the Phase 3 B-LONG and Kids B-LONG studies. However, long-term rFIXFc safety and efficacy data have not yet been reported. AIM: To report long-term rFIXFc safety and efficacy in subjects with haemophilia B. METHODS: B-YOND (NCT01425723) was an open-label extension for eligibl previously treated subjects who completed B-LONG or Kids B-LONG. Subjects received ≥1 treatment regimen: weekly prophylaxis (WP), individualized interval prophylaxis (IP), modified prophylaxis or episodic treatment. Subjects could switch regimens at any time. The primary endpoint was inhibitor development. RESULTS: Ninety-three subjects from B-LONG and 27 from Kids B-LONG (aged 3-63 years) were enrolled. Most subjects received WP (B-LONG: n = 51; Kids B-LONG: n = 23). For subjects from B-LONG, median (range) treatment duration was 4.0 (0.3-5.4) years and median (range) number of exposure days (EDs) was 146 (8-462) EDs. Corresponding values for paediatric subjects were 2.6 (0.2-3.9) years and 132 (50-256) EDs. No inhibitors were observed (0 per 1000 subject-years; 95% confidence interval, 0-8.9) and the overall rFIXFc safety profile was consistent with prior studies. Annualized bleed rates remained low and extended-dosing intervals were maintained for most subjects. Median dosing interval for the IP group was approximately 14 days for adults and adolescents (n = 31) and 10 days for paediatric subjects (n = 5). CONCLUSIONS: B-YOND results confirm the long-term (up to 5 years, with cumulative duration up to 6.5 years) well-characterized safety and efficacy of rFIXFc treatment for haemophilia B.
INTRODUCTION: Recombinant factor IX Fc fusion protein (rFIXFc) has demonstrated efficacy for treatment of haemophilia B in the Phase 3 B-LONG and Kids B-LONG studies. However, long-term rFIXFc safety and efficacy data have not yet been reported. AIM: To report long-term rFIXFc safety and efficacy in subjects with haemophilia B. METHODS: B-YOND (NCT01425723) was an open-label extension for eligibl previously treated subjects who completed B-LONG or Kids B-LONG. Subjects received ≥1 treatment regimen: weekly prophylaxis (WP), individualized interval prophylaxis (IP), modified prophylaxis or episodic treatment. Subjects could switch regimens at any time. The primary endpoint was inhibitor development. RESULTS: Ninety-three subjects from B-LONG and 27 from Kids B-LONG (aged 3-63 years) were enrolled. Most subjects received WP (B-LONG: n = 51; Kids B-LONG: n = 23). For subjects from B-LONG, median (range) treatment duration was 4.0 (0.3-5.4) years and median (range) number of exposure days (EDs) was 146 (8-462) EDs. Corresponding values for paediatric subjects were 2.6 (0.2-3.9) years and 132 (50-256) EDs. No inhibitors were observed (0 per 1000 subject-years; 95% confidence interval, 0-8.9) and the overall rFIXFc safety profile was consistent with prior studies. Annualized bleed rates remained low and extended-dosing intervals were maintained for most subjects. Median dosing interval for the IP group was approximately 14 days for adults and adolescents (n = 31) and 10 days for paediatric subjects (n = 5). CONCLUSIONS: B-YOND results confirm the long-term (up to 5 years, with cumulative duration up to 6.5 years) well-characterized safety and efficacy of rFIXFc treatment for haemophilia B.
Authors: Pratima Chowdary; Margareta Holmström; Johnny N Mahlangu; Margaret C Ozelo; Ingrid Pabinger; K John Pasi; Margaret V Ragni; Amy Shapiro; Chris Barnowski; Stefan Lethagen Journal: Res Pract Thromb Haemost Date: 2022-07-26