An Open-Label Extension Study to Assess the Long-Term Efficacy and Safety of a Plasma-Derived von Willebrand Factor (VWF)/Factor VIII (FVIII) Concentrate in Patients with von Willebrand Disease (SWIFT-VWDext Study)

Toshko Lissitchkov; Anna Klukowska; Evgeny Buevich; Irina Maltceva; Guenter Auerswald; Oleksandra Stasyshyn; Wilfried Seifert; Tobias Rogosch

doi:10.2147/JBM.S268907

An Open-Label Extension Study to Assess the Long-Term Efficacy and Safety of a Plasma-Derived von Willebrand Factor (VWF)/Factor VIII (FVIII) Concentrate in Patients with von Willebrand Disease (SWIFT-VWDext Study)

J Blood Med. 2020 Oct 9:11:345-356. doi: 10.2147/JBM.S268907. eCollection 2020.

Authors

Toshko Lissitchkov¹, Anna Klukowska², Evgeny Buevich³, Irina Maltceva³, Guenter Auerswald⁴, Oleksandra Stasyshyn⁵, Wilfried Seifert⁶, Tobias Rogosch⁶

Affiliations

¹ Specialized Hospital for Active Treatment (SHAT), Sofia, Bulgaria.
² Department of Paediatrics, Haematology and Oncology of Warsaw Medical University, Warsaw, Poland.
³ GOUVPO Altaysky State Medical University of Roszdrav, Bernaul, Russian Federation.
⁴ Prof. Hess Kinderklinik, Klinikum Bremen-Mitte, Bremen, Germany.
⁵ Institute of Pathology and Transfusion Medicine AMN, Lviv, Ukraine.
⁶ Clinical Development, CSL Behring, Marburg, Germany.

Abstract

Objective: 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: hemostatic efficacy; on-demand; prophylaxis; safety; surgery; von Willebrand disease.

Grants and funding

This study was supported by a grant from CSL Behring, Australia.