Recombinant factor VIII Fc fusion protein for the treatment of severe haemophilia A: Final results from the ASPIRE extension study

Authors: Nolan B., Mahlangu J., Pabinger I., Young G., Konkle B. A., Barnes C., Nogami K., Santagostino E., Pasi KJ., Khoo L., Winding B., Yuan H., Fruebis J., Rudin D., Oldenburg J.

Publication: Haemophilia; April 2020

Affiliations: Children’s Health Ireland at Crumlin, Dublin, Ireland ; Haemophilia Comprehensive Care Centre, Faculty of Health Sciences, Charlotte Maxeke Johannesburg Academic Hospital and NHLS, University of Witwatersrand, Johannesburg, South Africa; Medizinische Universitat Wien, Vienna, Austria; Children’s Hospital Los Angeles, Los Angeles, CA, USA ; University of Southern California Keck School of Medicine, Los Angeles, CA, USA ; Bloodworks Northwest, Seattle, WA, USA; The Royal Children’s Hospital, Parkville, Vic., Australia; Nara Medical University, Kashiwara, Japan; Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy; Royal London Haemophilia Centre, Barts and The London School of Medicine and Dentistry, London, UK; Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sobi, Stockholm, Sweden; Sanofi, Cambridge, MA, USA; Bioverativ, a Sanofi company, Waltham, MA, USA; Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.

Abstract: INTRODUCTION: The efficacy and safety of recombinant factor VIII Fc fusion protein (rFVIIIFc) as an extended half-life treatment for severe haemophilia A were demonstrated in the Phase 3 A-LONG and Kids A-LONG studies. Eligible subjects who completed A-LONG and Kids A-LONG could enrol in ASPIRE (NCT01454739), an open-label extension study. AIM: To report the long-term safety and efficacy of rFVIIIFc in subjects with severe haemophilia A who enrolled in ASPIRE. METHODS: Previously treated subjects received one or more of the following regimens: individualized prophylaxis (IP), weekly prophylaxis, modified prophylaxis or episodic treatment. Subjects could switch treatment regimen at any time. The primary endpoint was inhibitor development. RESULTS: A total of 150 subjects from A-LONG and 61 subjects from Kids A-LONG enrolled in ASPIRE. Most subjects received the IP regimen (A-LONG: n = 110; Kids A-LONG: n = 59). Median (range) treatment duration in ASPIRE for subjects from A-LONG and Kids A-LONG was 3.9 (0.1-5.3) years and 3.2 (0.3-3.9) years, respectively. No inhibitors were observed (0 per 1000 subject-years; 95% confidence interval, 0-5.2) and the overall rFVIIIFc safety profile was consistent with prior studies. For subjects on the IP regimen, annualized bleed rates (ABR) remained low (median overall ABR for adults and adolescents was <1.0) and extended-dosing intervals were maintained (median of 3.5 days) for the majority of subjects in ASPIRE. CONCLUSION: ASPIRE results, which include up to 5 years of follow-up data, confirm earlier reports on the consistent and well-characterized safety and efficacy of rFVIIIFc treatment for severe haemophilia A.