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; Abel Hassoun; Bénédicte Wibaut; Annie Harroche; Christine Biron-Andréani; Yohan Repesse; Roseline d'Oiron; Brigitte Tardy; Brigitte Pan Petesch; Pierre Chamouni; Valérie Gay; Marc Fouassier; Claire Pouplard; Cédric Martin; Hasan Catovic; Xavier Delavenne

doi:10.1055/s-0043-1761449

Thrombosis and Haemostasis, Table of Contents

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

¹Haemophilia Treatment Center, University Hospital, Rennes, France

²Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France

,

Abel Hassoun

³Haemophilia Treatment Center, Simone Veil Hospital, GH Eaubonne-Montmorency, France

,

Bénédicte Wibaut

⁴Haemophilia Treatment Centre, National Reference Willebrand Centre, University Hospital, Lille, France

,

Annie Harroche

⁵Department of Hematology, Haemophilia Treatment Centre, University Hospital Necker Enfants Malades, Paris, France

,

Christine Biron-Andréani

⁶Haemophilia Treatment Centre, University Hospital, Montpellier, France

,

Yohan Repesse

⁷Haematology Laboratory and Haemophilia Reference Centre, Centre Hospitalier Universitaire de Caen, Caen, France

,

Roseline d'Oiron

⁸CRH, 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

⁹HITh, UMR_S1176, INSERM, Université Paris-Saclay, Le Kremlin Bicêtre, France

,

Brigitte Tardy

¹⁰Haemophilia Treatment Center, University Hospital, Saint-Etienne, France

¹¹Inserm CIC 1408, Saint-Etienne University Hospital Center, Saint-Etienne, France

,

Brigitte Pan Petesch

¹²Haemophilia Treatment Center, Morvan University Hospital, Saint-Etienne Brest, France

,

Pierre Chamouni

¹³Haemophilia Treatment Center, University Hospital, Rouen, France

,

Valérie Gay

¹⁴Haemophilia Treatment Center, Hospital, Chambery, France

,

Marc Fouassier

¹⁵Haemophilia Treatment Center, Hôtel-Dieu University Hospital, Nantes, France

,

Claire Pouplard

¹⁶Haemophilia Treatment Center, Hospital, Tours, France

,

Cédric Martin

¹⁷CSL Behring, Paris, France

,

Hasan Catovic

¹⁷CSL Behring, Paris, France

,

Xavier Delavenne

¹⁸INSERM, UMR 1059, Dysfonction Vasculaire et de l'Hémostase, Université de Lyon, Saint Etienne, France

¹⁹Laboratoire de Pharmacologie – Toxicologie, CHU de Saint-Etienne, Saint-Etienne, France

› Author Affiliations

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

Full Text

References

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Supplementary Material

Supplementary Material