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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, GermanyCorrespondence: Guenter AuerswaldHess Kinderklinik, Klinikum Bremen-Mitte, Bremen, GermanyTel +49 176-10113362Email guenterauerswald@aol.comPurpose: 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 |
