Prophylaxis with a recombinant factor VIII Fc in hemophilia A: long-term follow-up on joint health, efficacy, and safety from phase 3 studies in children and adults

Barbara A Konkle; Johannes Oldenburg; John Pasi; Roshni Kulkarni; Beatrice Nolan; Johnny Mahlangu; Guy Young; Simon A Brown; Ingrid Pabinger; Amy Shapiro; Claude Négrier; Victor Blanchette; Margaret V Ragni; Jennifer Dumont; Stefan Lethagen

doi:10.1016/j.rpth.2023.102180

Prophylaxis with a recombinant factor VIII Fc in hemophilia A: long-term follow-up on joint health, efficacy, and safety from phase 3 studies in children and adults

Res Pract Thromb Haemost. 2023 Aug 22;7(6):102180. doi: 10.1016/j.rpth.2023.102180. eCollection 2023 Aug.

Authors

Barbara A Konkle^{1

2}, Johannes Oldenburg³, John Pasi⁴, Roshni Kulkarni⁵, Beatrice Nolan⁶, Johnny Mahlangu⁷, Guy Young⁸, Simon A Brown⁹, Ingrid Pabinger¹⁰, Amy Shapiro¹¹, Claude Négrier¹², Victor Blanchette¹³, Margaret V Ragni¹⁴, Jennifer Dumont¹⁵, Stefan Lethagen^{16

17}

Affiliations

¹ Washington Center for Bleeding Disorders, Seattle, Washington, USA.
² Division of Hematology, University of Washington, Seattle, Washington, USA.
³ Institute of Experimental Hematology and Transfusion Medicine University Clinic Bonn, Bonn, Germany.
⁴ Royal London Haemophilia Centre, Barts and the London School of Medicine and Dentistry, London, UK.
⁵ Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan, USA.
⁶ Children's Health Ireland at Crumlin, Dublin, Ireland.
⁷ Hemophilia Comprehensive Care Centre, Department of Molecular Medicine and Hematology, Faculty of Health Sciences, University of the Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa.
⁸ Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
⁹ Queensland Children's Hospital, Brisbane, QLD, Australia.
¹⁰ Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
¹¹ Indiana Hemophilia & Thrombosis Center, Indianapolis, Indiana, USA.
¹² Division of Hematology, University Claude Bernard Lyon I, Lyon, France.
¹³ Department of Pediatrics and Child Health Evaluative Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
¹⁴ Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁵ Sanofi, Waltham, Massachusetts, USA.
¹⁶ Swedish Orphan Biovitrum AB, Stockholm, Sweden.
¹⁷ Copenhagen University, Copenhagen, Denmark.

Abstract

Background: Recurrent joint bleeds are a major cause of morbidity in severe hemophilia. Prophylaxis with efmoroctocog alfa (a recombinant factor VIII Fc fusion protein, [rFVIIIFc]) has demonstrated benefits beyond bleed control, including joint health maintenance.

Objectives: To assess long-term efficacy and safety of rFVIIIFc prophylaxis in severe hemophilia A in phase 3 pivotal (A-LONG/Kids A-LONG) and extension (ASPIRE) studies.

Methods: Longitudinal analysis included pooled data from A-LONG/Kids A-LONG and ASPIRE. Subgroup analyses investigated outcomes in modified Hemophilia Joint Health Score or Hemophilia Joint Health Score and target joints in subjects with 4 to 5 years follow-up on individualized prophylaxis (IP), and those with the highest annualized bleeding rate (ABR) quartile during Year 1 of IP.

Results: Overall, rFVIIIFc consumption remained stable and low ABRs were maintained, with a median treatment duration of 4.2/3.4 years in subjects from A-LONG/Kids A-LONG, respectively. Median overall ABR also remained low (1.0-2.0) in subjects on IP for 4 to 5 years. Sustained improvements in modified Hemophilia Joint Health Score or Hemophilia Joint Health Score were demonstrated over a median follow-up of 3.7 years. In subjects from A-LONG/Kids A-LONG, 99.6% (n = 234)/100% (n = 9) of evaluable baseline target joints were resolved, with no recurrence in 95%/100% of target joints. In IP subjects within the highest ABR quartile in Year 1, continued improvements were observed over a median follow-up of 4.3 years in ABR and joint health, without increased factor consumption. No inhibitors or treatment-related serious adverse events were reported.

Conclusion: Previously treated subjects of all ages receiving long-term prophylaxis with rFVIIIFc had sustained clinical benefits, including improved joint health and low ABR.

Keywords: factor VIII; hemophilia A; joints; rFVIIIFc; recombinant fusion protein.