OR14
Recombinant von Willebrand Factor Prophylaxis for Severe von Willebrand Disease: Final Results Focusing on Adults Receiving Once Weekly Prophylaxis in a Phase 3b Continuation Study
S. Susen1,*, F. W. G. Leebeek2, G. Castaman3, A. L. Dunn4, M. A. Timofeeva5, C. Montcrieff6, M. Waliullah6, J. Zhang6
1University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France, 2Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands, 3Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy, 4Department of Hematology, Oncology, Bone Marrow Transplant and Apheresis, Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, United States, 5Federal State Budgetary Scientific Institution Kirov Scientific-Research Institute of Hematology and Blood Transfusion of Federal Medical and Biological Agency, Kirov, Russian Federation, 6Takeda Development Center Americas, Inc., Cambridge, United States
Introduction: Recombinant von Willebrand factor (rVWF, Takeda Pharmaceuticals U.S.A., Inc.) product labels recommend 40–60 IU/kg prophylaxis twice weekly in adults with von Willebrand disease (VWD); however, an individualized reduced dosing frequency may reduce treatment burden. We present final data for adults (≥18 years) with severe VWD (baseline VWF:ristocetin cofactor <20 IU/dL) who received rVWF prophylaxis in an open-label, prospective, multicenter, Phase 3b continuation study (NCT03879135), focusing on a post hoc analysis of adult participants (pts) who received once weekly (QW) dosing.
Methods: The study enrolled rollover pts from a Phase 3 adult prophylaxis study (NCT02973087) and non-rollover pts who had ≥3 treated spontaneous bleeding events (BEs) and had received on-demand (OD) treatment with VWF products in the prior 12 months (mos). Pts received 1–3 years’ rVWF prophylaxis, starting with 50±10 IU/kg (up to 80 IU/kg) 1–3 times weekly, tailored based on pharmacokinetics, BE history and dose in the parent study. The primary endpoint was annualized bleeding rate of treated spontaneous BEs (sABR) over the first 12 mos’ rVWF prophylaxis.
Results: Fourteen adult pts enrolled to receive rVWF prophylaxis (rollover n=11); starting regimens were QW (n=5), twice weekly (n=8), or 3 times weekly (n=1). For the 5 pts on QW dosing (rollover n=2; non-rollover n=3), median(range) age was 35.0(25–77) years, 4 pts were White, 2 were female, 4 had Type 2A and 1 had Type 3 VWD. All 5 pts completed the study with 35–36 mos’ treatment. Median(range) 12-mo sABR was 1.0(0.00–3.12), similar to all prophylaxis pts (1.0[0.00–7.47]); for the 3 non-rollover pts, sABR reduced compared with their historical sABR while on OD therapy (Table). The 2 rollover pts maintained a similarly low sABR (0 and 0.33) as in the parent prophylaxis study. The mean(SD) weekly dose and number of infusions were 63.8(10.42) IU/kg and 1.1(0.16), respectively. After ~2 years on QW dosing, only 2 pts had their dose escalated to twice weekly for breakthrough BEs. No rVWF-related adverse events, hypersensitivity reactions or thromboembolic events occurred in pts with prophylaxis, and there were no instances of inhibitor development.
Discussion/Conclusion: Once weekly rVWF prophylaxis can be an efficacious treatment option with a favorable safety profile for adults with severe VWD.
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Disclosure of Interest: S. Susen Grant/Research support from: The National Research Agency and National Ministry of Health, Consultant for: Novo Nordisk, Sanofi, LFB, Pfizer, and Takeda. Payment or honoraria from Biomarin, Bioverativ, CSL Behring, CorWave, LFB, Roche-Chugai, Sanofi, Takeda, Siemens Healthineers, Sobi, and Stago. Support for attending meetings and/or travel from Sobi, Novo Nordisk, and LFB. Serves as leadership for the French Society of Thrombosis and Haemostasis and French Society of Haematology, F. Leebeek Grant/Research support from: CSL Behring, Takeda and Sobi , Consultant for: CSL Behring, Takeda and Biomarin of which the fees go to the university, G. Castaman Consultant for: Bayer, BioMarin, CSL Behring, Grifols, Kedrion, LFB, Novo Nordisk, Roche, Sanofi, Sobi, Takeda, and uniQure, A. Dunn Grant/Research support from: Dr Dunn’s institution received research funding on her behalf from Biomarin, Spark, Regeneron, ATHN, Takeda, Sanofi/Sobi, and Novo Nordisk, Consultant for: Hema Biologics, CSL, Medscape Behring/Uniqure, M. Timofeeva: None declared, C. Montcrieff Shareholder of: Takeda, Employee of: Takeda Development Center Americas, Inc., Cambridge, MA, USA, M. Waliullah Employee of: Contractor for Takeda Development Center Americas, Inc., Cambridge, MA, USA, J. Zhang Shareholder of: Takeda, Employee of: Takeda Development Center Americas, Inc., Cambridge, MA, USA