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Pharmacokinetics, Efficacy and Safety of a Plasma-Derived VWF/FVIII Concentrate (Formulation V) in Pediatric Patients with von Willebrand Disease (SWIFTLY-VWD Study)

Authors Auerswald G, Djambas Khayat C, Stasyshyn O, Iosava G, Romashevskaya I, López MJ, Seifert W, Rogosch T

Received 31 October 2019

Accepted for publication 18 March 2020

Published 22 June 2020 Volume 2020:11 Pages 213—225

DOI https://doi.org/10.2147/JBM.S236789

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Martin H. Bluth


Guenter Auerswald,1 Claudia Djambas Khayat,2 Oleksandra Stasyshyn,3 Genadi Iosava,4 Irina Romashevskaya,5 Marta Julia López,6 Wilfried Seifert,7 Tobias Rogosch7

1Hess Kinderklinik, Klinikum Bremen-Mitte, Bremen, Germany; 2Hotel Dieu de France Hospital, St Joseph University, Beirut, Lebanon; 3Institute of Blood Pathology and Transfusion Medicine, Academy of Medical Sciences of Ukraine, Lviv, Ukraine; 4Institute for Hematology and Transfusiology, Tbilisi, Georgia; 5Republican Research Centre for Radiation Medicine and Human Ecology, Gomel, Belarus; 6Hematology, Hospital Roosevelt, Guatemala, Guatemala; 7Clinical Development, CSL Behring, Marburg, Germany

Correspondence: Guenter Auerswald
Hess Kinderklinik, Klinikum Bremen-Mitte, Bremen, Germany
Tel +49 176-10113362
Email guenterauerswald@aol.com

Purpose: Formulation V (VONCENTO®) is a plasma-derived high-concentration/low-volume, high-purity von Willebrand factor (VWF)/factor VIII (FVIII) concentrate, originally indicated for von Willebrand disease (VWD) in adults and adolescents. This multicenter, open-label study (SWIFTLY-VWD) evaluated the pharmacokinetics (PK), as well as hemostatic efficacy and safety, of Formulation V in pediatric patients (< 12 years) with severe VWD requiring treatment or prophylaxis of bleedings.
Methods: PK investigations were performed following one dose of Formulation V at Day 1 and 180. Nonsurgical bleeds were analyzed, while hemostatic efficacy was graded as excellent/good/moderate/none. Safety assessments included adverse events, and presence of VWF and/or FVIII inhibitors.
Results: Formulation V was administered as on-demand (N=13) or prophylaxis therapy (N=4) for 12 months (< 6 years, N=9; 6 to < 12 years, N=8). PK parameters for VWF markers were generally comparable to adults but showed lower VWF:ristocetin cofactor (RCo) exposure. Incidence of major bleeds was lower for prophylaxis (3.3%) than on-demand therapy (27.1%); joint bleeds were also lower (3.3% vs 11.5%, respectively). Investigator-reported excellent/good hemostatic efficacy against nonsurgical bleeds was 100%. No clinically relevant differences in PK, hemostatic efficacy, or safety were observed between age-groups (< 6 years and 6 to < 12 years). Formulation V was well tolerated. Adverse events were mild–moderate and consistent with the adult safety profile. No cases of anaphylactic reactions or angioedema, development of FVIII/VWF inhibitors, thromboembolic events, or viral infections were reported.
Conclusion: This study provides evidence for use of Formulation V to treat and prevent bleeding in pediatric patients with severe VWD, and led to the European approval of Formulation V in children.

Keywords: von Willebrand disease, clinical trial, pediatrics, prophylaxis, von Willebrand factor-factor VIII concentrate

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