Long-term safety and sustained efficacy for up to 5 years of treatment with recombinant factor IX Fc fusion protein in subjects with haemophilia B: Results from the B-YOND extension study

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

Affiliations

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.

PMID: 32497409
DOI: 10.1111/hae.14036

Long-term safety and sustained efficacy for up to 5 years of treatment with recombinant factor IX Fc fusion protein in subjects with haemophilia B: Results from the B-YOND extension study

K John Pasi et al. Haemophilia. 2020 Nov.

. 2020 Nov;26(6):e262-e271.

doi: 10.1111/hae.14036. Epub 2020 Jun 4.

Authors

Affiliations

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.

PMID: 32497409
DOI: 10.1111/hae.14036

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.

Keywords: bleed rate; extended half-life; factor IX; haemophilia B; individualized prophylaxis; perioperative haemostasis; rFIXFc.

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References

REFERENCES

1. Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19:e1-47.
1. National Hemophilia Foundation. MASAC document 241: MASAC recommendations concerning Prophylaxis. https://www.hemophilia.org/Researchers-Healthcare-Providers/Medical-and-.... Accessed 25 October 2018.
1. Gringeri A, Lundin B, Von Mackensen S, Mantovani L, Mannucci PM, The ESPIRIT Study Group. A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study). J Thromb Haemost. 2011;9:700-710.
1. Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357:535-544.
1. Castaman G. The benefits of prophylaxis in patients with hemophilia B. Expert Rev Hematol. 2018;11:673-683.

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The B-YOND study was sponsored by Sanofi (Cambridge, MA, USA) and Sobi (Stockholm, Sweden)

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Long-term safety and sustained efficacy for up to 5 years of treatment with recombinant factor IX Fc fusion protein in subjects with haemophilia B: Results from the B-YOND extension study

Affiliations

Long-term safety and sustained efficacy for up to 5 years of treatment with recombinant factor IX Fc fusion protein in subjects with haemophilia B: Results from the B-YOND extension study

Authors

Affiliations

Abstract

References

REFERENCES

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources