Announcement
Thank you for attending THSNA 2026. The virtual meeting is now closed.
Thank you for attending THSNA 2026. The virtual meeting is now closed.
Presentation Details
| 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 Sophie Susen1, Frank W G Leebeek2, Giancarlo Castaman3, Amy L Dunn4, Margarita A Timofeeva5, Caitlin Montcrieff6, Maria Waliullah7, Jingmei Zhang7. 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, OH, USA.5Federal State Budgetary Scientific Institution, Kirov Scientific-Research Institute of Hematology and Blood Transfusion of Federal Medical and Biological Agency, Kirov, Russia.6Takeda Pharmaceuticals U.S.A., Inc., Lexington, MA, USA.7Takeda Development Center Americas, Inc., Cambridge, MA, USA |
Abstract
Background: The product labels of recombinant von Willebrand factor (rVWF; Takeda Pharmaceuticals U.S.A., Inc.) recommend prophylaxis at 40–60 IU/kg twice weekly in adults with von Willebrand disease (VWD); however, an individualized reduced dosing frequency may reduce treatment burden.
Objectives: 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 who received once weekly dosing. Methods: The study’s prophylaxis cohorts enrolled rollover participants from a phase 3 adult prophylaxis study (NCT02973087) and non-rollover participants who had ≥3 treated spontaneous bleeding events (BEs) and had received on-demand treatment with VWF products in the prior 12 months. Participants received 1–3 years of prophylaxis with rVWF, starting with 50 ± 10 IU/kg (up to 80 IU/kg) 1–3 times weekly, tailored based on pharmacokinetics, BE history, and prophylactic dose in the parent study. The annualized bleeding rate of treated spontaneous BEs (tsABR) was evaluated over the first 12 months of rVWF prophylaxis (primary endpoint) and for the entire study treatment period. Results: Fourteen adult participants were enrolled to receive rVWF prophylaxis (rollover n = 11); starting regimens were once weekly (n = 5), twice weekly (n = 8), or 3 times weekly (n = 1). For the 5 participants receiving once weekly dosing (rollover n = 2; non-rollover n = 3), median (range) age was 35.0 (25–77) years, 4 participants were White, 2 were female, 4 had Type 2A VWD and 1 had Type 3 VWD. All 5 participants completed the study with 35–36 months’ treatment, and median (range) 12-month tsABR was 1.0 (0.0–3.1), similar to all prophylaxis participants (N = 14, 1.0 [0.00–7.47]). For the 3 non-rollover participants, tsABR was lower than their historical tsABR while receiving on-demand therapy (Table). One rollover participant, who received once weekly rvWF prophylaxis and had no treated BEs in the parent phase 3 study, continued weekly dosing and maintained a tsABR of 0 in the continuation study. Another rollover participant who reduced dosing from twice weekly to weekly had a small increase in tsABR in the continuation study (from 0 to 0.33). The mean (SD) weekly dose and number of infusions were 63.8 (10.4) IU/kg and 1.1 (0.2), respectively, for the entire study period. Only 2 participants escalated their dose to twice weekly during the study (after ~2 years of once weekly dosing); one escalated at study day 717 and one escalated at day 805 for 2 weeks and then on day 1032 until the end of the study. No rVWF-related adverse events, hypersensitivity reactions, or thromboembolic events occurred in participants with prophylaxis, and there were no instances of VWF or FVIII inhibitor development. Conclusions: Once weekly rVWF prophylaxis can be an efficacious treatment option with a favorable safety profile for adults with severe VWD and offers a flexible dosing option that can achieve the desired treatment effect while reducing treatment burden.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
Objectives: 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 who received once weekly dosing. Methods: The study’s prophylaxis cohorts enrolled rollover participants from a phase 3 adult prophylaxis study (NCT02973087) and non-rollover participants who had ≥3 treated spontaneous bleeding events (BEs) and had received on-demand treatment with VWF products in the prior 12 months. Participants received 1–3 years of prophylaxis with rVWF, starting with 50 ± 10 IU/kg (up to 80 IU/kg) 1–3 times weekly, tailored based on pharmacokinetics, BE history, and prophylactic dose in the parent study. The annualized bleeding rate of treated spontaneous BEs (tsABR) was evaluated over the first 12 months of rVWF prophylaxis (primary endpoint) and for the entire study treatment period. Results: Fourteen adult participants were enrolled to receive rVWF prophylaxis (rollover n = 11); starting regimens were once weekly (n = 5), twice weekly (n = 8), or 3 times weekly (n = 1). For the 5 participants receiving once weekly dosing (rollover n = 2; non-rollover n = 3), median (range) age was 35.0 (25–77) years, 4 participants were White, 2 were female, 4 had Type 2A VWD and 1 had Type 3 VWD. All 5 participants completed the study with 35–36 months’ treatment, and median (range) 12-month tsABR was 1.0 (0.0–3.1), similar to all prophylaxis participants (N = 14, 1.0 [0.00–7.47]). For the 3 non-rollover participants, tsABR was lower than their historical tsABR while receiving on-demand therapy (Table). One rollover participant, who received once weekly rvWF prophylaxis and had no treated BEs in the parent phase 3 study, continued weekly dosing and maintained a tsABR of 0 in the continuation study. Another rollover participant who reduced dosing from twice weekly to weekly had a small increase in tsABR in the continuation study (from 0 to 0.33). The mean (SD) weekly dose and number of infusions were 63.8 (10.4) IU/kg and 1.1 (0.2), respectively, for the entire study period. Only 2 participants escalated their dose to twice weekly during the study (after ~2 years of once weekly dosing); one escalated at study day 717 and one escalated at day 805 for 2 weeks and then on day 1032 until the end of the study. No rVWF-related adverse events, hypersensitivity reactions, or thromboembolic events occurred in participants with prophylaxis, and there were no instances of VWF or FVIII inhibitor development. Conclusions: Once weekly rVWF prophylaxis can be an efficacious treatment option with a favorable safety profile for adults with severe VWD and offers a flexible dosing option that can achieve the desired treatment effect while reducing treatment burden.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.