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Toshko Lissitchkov,1 Anna Klukowska,2 Evgeny Buevich,3 Irina Maltceva,3 Guenter Auerswald,4 Oleksandra Stasyshyn,5 Wilfried Seifert,6 Tobias Rogosch6 1Specialized Hospital for Active Treatment (SHAT), Sofia, Bulgaria; 2Department of Paediatrics, Haematology and Oncology of Warsaw Medical University, Warsaw, Poland; 3GOUVPO Altaysky State Medical University of Roszdrav, Bernaul, Russian Federation; 4Prof. Hess Kinderklinik, Klinikum Bremen-Mitte, Bremen, Germany; 5Institute of Pathology and Transfusion Medicine AMN, Lviv, Ukraine; 6Clinical Development, CSL Behring, Marburg, GermanyCorrespondence: Toshko LissitchkovSpecialized Hospital for Active Treatment (SHAT) “JOAN PAVEL”, 67A Stoletov Blvd, Sofia 1233, BulgariaTel +35 989 436 9096Email t_lissitchkov@yahoo.comObjective: Plasma-derived von Willebrand factor/factor VIII (pdVWF/FVIII; VONCENTO®, CSL Behring) is a high-concentration, low-volume, high-purity concentrate, which contains a high level of high-molecular-weight multimers and a VWF/FVIII ratio of ∼ 2.4:1. The SWIFT (“Studies with von Willebrand factor/Factor VIII”) program is evaluating pdVWF/FVIII in patients with von Willebrand disease (VWD). The long-term efficacy and safety profile of pdVWF/FVIII was investigated in this multicenter, open-label, extension study.Methods: Pediatric, adolescent, and adult patients with VWD who required treatment of non-surgical bleeds (NSBs), treatment during surgical events or who were receiving prophylaxis and who had completed one of two previous clinical trials of pdVWF/FVIII were included. Efficacy and safety analyses were performed for on-demand (n=10), prophylaxis (n=8), or on-demand and prophylaxis (n=2) treatment in patients pre-treated with pdVWF/FVIII for ≥ 12 months.Results: Seven patients experienced a total of 402 NSBs in the on-demand arm, of which 77 required treatment and nine NSB events in three patients were considered major. Nine patients reported 118 NSBs in the prophylaxis arm, with 96 events requiring treatment and seven patients experiencing 12 major NSB events. Excellent or good hemostatic efficacy was reported by the investigator for 98.7% (on-demand) and 97.9% (prophylaxis) of NSB events treated with pdVWF/FVIII, without relevant differences between subgroups by age. pdVWF/FVIII was well tolerated, and the adverse events seen were mild-moderate and consistent with the safety profile for this product seen in other studies. There were no cases of anaphylactic reactions and angioedema, development of VWF/FVIII inhibitors, thromboembolic events, or viral infections.Conclusion: This contemporary comprehensive development program evaluating pdVWF/FVIII across all ages demonstrates long-term safety and efficacy for treatment and prevention of bleeds in patients with severe VWD, supporting the benefit–risk profile of pdVWF/FVIII.Keywords: von Willebrand disease, hemostatic efficacy, safety, prophylaxis, on-demand, surgery

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