A French Real-World Evidence Study Evaluating the Efficacy, Safety, and Pharmacokinetic Parameters of rVIII-SingleChain in Patients with Hemophilia A Receiving Prophylaxis

Authors: Guillet, B; Hassoun, A; Wibaut, B; Harroche, A; Biron-Andréani, C; Repesse, Y; D’Oiron, R; Tardy, B; Pan Petesch, B; Chamouni, P; Gay, V; Fouassier, M; Pouplard, C; Martin, C; Catovic, H; Delavenne, X

Affiliations: Haemophilia Treatment Center, University Hospital, Rennes, France. Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) – UMR_S 1085, Rennes, France. (…) Haemophilia Treatment Center, Simone Veil Hospital, GH Eaubonne-Montmorency, France. Haemophilia Treatment Centre, National Reference Willebrand Centre, University Hospital, Lille, France. CSL Behring, Paris, France. INSERM, UMR 1059, Dysfonction Vasculaire et de l’Hémostase, Université de Lyon, Saint Etienne, France. Laboratoire de Pharmacologie – Toxicologie, CHU de Saint-Etienne, Saint-Etienne, France.

Publication: Thromb Haemost ; 2023

Abstract : BACKGROUND : rVIII-SingleChain is a recombinant factor VIII (FVIII) with increased binding affinity to von Willebrand factor compared with other FVIII products. rVIII-SingleChain is indicated for the treatment and prevention of bleeding episodes in patients with hemophilia A. OBJECTIVES: To collect real-world evidence data from patients treated with rVIII-SingleChain to confirm the efficacy and safety established in the clinical trial program and carry out a population pharmacokinetic (PK) analysis. PATIENTS/METHODS: This interim analysis includes data, collected between January 2018 – September 2021, from patients treated with rVIII-SingleChain prophylaxis at French Hemophilia Treatment centers. Data on annualized bleeding rates, dosing frequency, and consumption before and after switching to rVIII-SingleChain were recorded. A population PK analysis was also conducted to estimate PK parameters. RESULTS: Overall, 43 patients switched to prophylaxis with rVIII-SingleChain either from a previous prophylaxis regimen or from on-demand treatment. Following the switch to rVIII-SingleChain, patients maintained excellent bleed control. After switching to rVIII-SingleChain, most patients maintained or reduced their regimen. Interestingly, a majority of patients treated >2 ×/weekly with a standard half-life FVIII reduced both injection frequency and FVIII consumption with rVIII-SingleChain. A PK analysis revealed a lower clearance of rVIII-SingleChain (1.9 vs. 2.1 dL/h) and a longer half-life both in adolescents/adults (n = 28) and pediatric (n = 6) patients (15.5 and 11.9 hours, respectively vs. 14.5 and 10.3 hours) than previously reported. CONCLUSIONS: Patients who switched to rVIII-SingleChain prophylaxis demonstrated excellent bleed control and a reduction in infusion frequency. A population PK analysis revealed improved PK parameters compared with those reported in the clinical trial.