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CC BY-NC-ND 4.0 · Thromb Haemost 2023; 123(05): 490-500
DOI: 10.1055/s-0043-1761449
Coagulation and Fibrinolysis

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

Benoit Guillet
1   Haemophilia Treatment Center, University Hospital, Rennes, France
2   Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France
,
Abel Hassoun
3   Haemophilia Treatment Center, Simone Veil Hospital, GH Eaubonne-Montmorency, France
,
Bénédicte Wibaut
4   Haemophilia Treatment Centre, National Reference Willebrand Centre, University Hospital, Lille, France
,
Annie Harroche
5   Department of Hematology, Haemophilia Treatment Centre, University Hospital Necker Enfants Malades, Paris, France
,
Christine Biron-Andréani
6   Haemophilia Treatment Centre, University Hospital, Montpellier, France
,
Yohan Repesse
7   Haematology Laboratory and Haemophilia Reference Centre, Centre Hospitalier Universitaire de Caen, Caen, France
,
Roseline d'Oiron
8   CRH, CRC-MHC (Centre de Référence de l'Hémophilie, Centre de Ressource et de Compétence des Maladies Hémorragiques Constitutionnelles), Hôpital Bicêtre, AP-HP, Université Paris-Saclay, Paris, France
9   HITh, UMR_S1176, INSERM, Université Paris-Saclay, Le Kremlin Bicêtre, France
,
Brigitte Tardy
10   Haemophilia Treatment Center, University Hospital, Saint-Etienne, France
11   Inserm CIC 1408, Saint-Etienne University Hospital Center, Saint-Etienne, France
,
Brigitte Pan Petesch
12   Haemophilia Treatment Center, Morvan University Hospital, Saint-Etienne Brest, France
,
Pierre Chamouni
13   Haemophilia Treatment Center, University Hospital, Rouen, France
,
Valérie Gay
14   Haemophilia Treatment Center, Hospital, Chambery, France
,
Marc Fouassier
15   Haemophilia Treatment Center, Hôtel-Dieu University Hospital, Nantes, France
,
Claire Pouplard
16   Haemophilia Treatment Center, Hospital, Tours, France
,
Cédric Martin
17   CSL Behring, Paris, France
,
Hasan Catovic
17   CSL Behring, Paris, France
,
Xavier Delavenne 
18   INSERM, UMR 1059, Dysfonction Vasculaire et de l'Hémostase, Université de Lyon, Saint Etienne, France
19   Laboratoire de Pharmacologie – Toxicologie, CHU de Saint-Etienne, Saint-Etienne, France
› Author Affiliations Funding The study was funded by CSL Behring.
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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.

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.

Keywords

factor VIII - extended half-life - hemophilia A - pharmacokinetic - outcome

Authors' Contribution

B. Guillet, C. Martin, and H. Catovic designed the study and analyzed data on safety and efficacy. X Delavenne performed the population PK analysis. B. Guillet, A. Hassoun, B. Wibaut, A. Harroche, C. Biron-Andreani, Y. Repesse, R. d'Oiron, B. Tardy, B. Pan Petesch, P. Chamouni, V. Gay, M. Fouassier, C. Pouplard, and X. Delavenne provided and reviewed the patient data. B. Guillet, C. Martin, H. Catovic, and X. Delavenne drafted the initial version of the manuscript. All authors critically reviewed and revised the manuscript and approved the final version.


Supplementary Material



Publication History

Received: 04 October 2022

Accepted: 22 December 2022

Article published online:
09 February 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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