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

Guenter Auerswald; Claudia Djambas Khayat; Oleksandra Stasyshyn; Genadi Iosava; Irina Romashevskaya; Marta Julia López; Wilfried Seifert; Tobias Rogosch

doi:10.2147/JBM.S236789

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

J Blood Med. 2020 Jun 22:11:213-225. doi: 10.2147/JBM.S236789. eCollection 2020.

Authors

Guenter Auerswald¹, Claudia Djambas Khayat², Oleksandra Stasyshyn³, Genadi Iosava⁴, Irina Romashevskaya⁵, Marta Julia López⁶, Wilfried Seifert⁷, Tobias Rogosch⁷

Affiliations

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

Abstract

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: clinical trial; pediatrics; prophylaxis; von Willebrand disease; von Willebrand factor-factor VIII concentrate.

Grants and funding

This study was supported by a grant from CSL Behring, which was responsible for operation of the trial, including study design, data collection and data analysis.