Long-term outcomes of prophylaxis with a recombinant factor VIII Fc or recombinant factor IX Fc in patients with hemophilia previously treated on demand

María-Teresa Álvarez-Román; Amy D Shapiro; Margaret V Ragni; Helena Palmborg; Linda Bystrická; Johan Szamosi; Sandra Casiano; Hervé Chambost

doi:10.1016/j.rpth.2023.102163

Long-term outcomes of prophylaxis with a recombinant factor VIII Fc or recombinant factor IX Fc in patients with hemophilia previously treated on demand

Res Pract Thromb Haemost. 2023 Aug 9;7(6):102163. doi: 10.1016/j.rpth.2023.102163. eCollection 2023 Aug.

Authors

María-Teresa Álvarez-Román¹, Amy D Shapiro², Margaret V Ragni³, Helena Palmborg⁴, Linda Bystrická⁴, Johan Szamosi⁴, Sandra Casiano⁵, Hervé Chambost⁶

Affiliations

¹ Department of Hematology, La Paz University Hospital-IdiPAZ, Madrid, Spain.
² Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana, USA.
³ Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh, and Hemophilia Center of Western PA, Pittsburgh, Pennsylvania, USA.
⁴ Swedish Orphan Biovitrum AB, Stockholm, Sweden.
⁵ Sanofi, Waltham, Massachusetts, USA.
⁶ AP-HM, Paediatric Haematology Department, Children's Hospital La Timone and Aix Marseille University, C2VN, Marseille, France.

Abstract

Background: Prophylactic factor replacement therapy is recommended over on-demand treatment for preserving long-term joint health in hemophilia. Extended half-life products, including efmoroctocog alfa/eftrenonacog alfa (recombinant factor VIII [FVIII]/FIX Fc fusion proteins; herein rFVIIIFc/rFIXFc), have the potential to reduce treatment burden with less frequent administration and improve bleed prevention.

Objectives: We report post hoc data from patients with hemophilia A or B (HA/HB) who switched from prestudy on-demand FVIII/FIX to rFVIIIFc/rFIXFc prophylaxis at the start of A-LONG/B-LONG or start of/during ASPIRE/B-YOND phase 3 studies.

Methods: Patients with ≥6 months rFVIIIFc/rFIXFc prophylaxis were enrolled. Treatment exposure, dosing, annualized bleeding rates, joint health, and health-related quality of life (HRQoL) outcomes were assessed. Results were also stratified by age.

Results: Sixty-seven patients with HA and 50 with HB were analyzed; ≥60% were from regions outside Europe/North America, predominately those aged 12 to ‍25 years. No subjects returned to on-demand treatment postswitch.After switch to rFVIIIFc/rFIXFc prophylaxis, median annualized bleeding rates were reduced and sustained at low levels with stable factor usage across age groups (median treatment duration: 4.8/3.6 years). HRQoL outcomes improved for all ages; most pronounced changes were in the sports and leisure and physical health domains. After switch to rFVIIIFc prophylaxis, total modified Hemophilia Joint Health Score and joints with pain decreased in 64.6% and 29.2% of patients with HA. Insufficient data from patients with HB limited joint health evaluation of rFIXFc.

Conclusions: Findings add to existing evidence and demonstrate the clinical and HRQoL benefits of switching patients from on-demand treatment to rFVIIIFc/rFIXFc prophylaxis.

Keywords: factor IX; factor VIII; hemophilia; prophylaxis; recombinant fusion proteins.