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

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.

• Authors: Guenter Auerswald, Claudia Djambas Khayat, Oleksandra Stasyshyn, Genadi Iosava, Irina Romashevskaya, Marta Julia López, Wilfried Seifert, Tobias Rogosch
• Journal: Journal of blood medicine (J Blood Med) Vol. 11 Pg. 213-225 ( 2020) ISSN: 1179-2736 [Print] New Zealand
• PMID: 32607039 (Publication Type: Journal Article)
• Copyright: © 2020 Auerswald et al.