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)

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:

• von Willebrand disease
• hemostatic efficacy
• safety
• prophylaxis
• on-demand
• surgery

Acknowledgments

The authors would like to thank Kazimierz Kuliczkowski for his input in the clinical study. Editorial support was provided by Meridian HealthComms and was funded by CSL Behring, Germany.

Abbreviations

DDAVP, desmopressin acetate (1-deamino-8-D-arginine vasopressin); FVIII, factor VIII; FVIII:C, factor VIII:coagulant activity; IU, international units; NSB, non-surgical bleeding; pdVWF/FVIII, plasma-derived von Willebrand factor/factor VIII; SAE, serious adverse event; TEAE, treatment-emergent adverse event; VWD, von Willebrand disease; VWF, von Willebrand factor; VWF:Ag, von Willebrand factor:antigen; VWF:CB, von Willebrand factor:collagen binding; VWF:RCo, von Willebrand factor:ristocetin cofactor.

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Disclosure

AK received fee for lectures and advisory board from CSL Behring, Sobi, Novo Nordisk, Takeda, Bioverativ, and Roche; GA received honoraria from CSL Behring for speeches at congresses and travel expenses; OS received fee for lectures from Novo Nordisk, Takeda and Roche; WS and TR are employees of CSL Behring. The authors report no other conflicts of interest in this work.

Additional information

Funding

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