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Presentation Details
| Safety and Efficacy of pdVWF/FVIII 1:1 Prophylaxis in Children Under 6 Years with Severe VWD: Results from the WIL-33 Study Akshat Jain1, Cindy Leissinger2, Vladimir Vdovin3, Pavel Zharkov4, Leonid Dubey5, Valentin Ţurea6, Zorica Trajkova Antevska7, Ester Zapotocka8, Bohumír Blažek9, Susan Halimeh10, Amanda Rodriguez11, Tarja-Elina Weisz12, Cristina Solomon13, Robert F.Sidonio Jr14. 1Medical Director Hemophilia Treatment Center, Loma Linda University School of Medicine, Loma Linda, CA, USA.2Tulane University, New Orleans, LA, USA.3Morozovskaya Children’s Hospital, Moscow, Russia.4Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.5Communal Institution of Lviv Regional Council, Western Ukrainian Specialized Children’s Medical Centre, Lviv, Ukrenia.6IMSP Mother and Child Institute, Chișinău, Moldova.7ERASE Zorica Trajkova Antevska, PHI University Clinic for Child Diseases, Skopje, Moldova.8Department of Pediatric Hematology and Oncology, University Hospital Motol and Second Faculty of Medicine, Charles University, Prague, Czech Republic.9University Hospital Ostrava, Ostrava, Czech Republic.10Gerinnungszentrum Rhein Ruhr, Duisburg, Germany.11Octapharma US, Paramus, NJ, USA.12Octapharma Pharmazeutika Produktionsgesellschaft m.b.H, Vienna, Austria.13Octapharma AG, Clinical Research and Development and Clinical Operations Haematology, Lachen, Switzerland.14Professor of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA |
Abstract
Background: Prophylaxis with von Willebrand factor (VWF) is recommended for individuals with von Willebrand disease (VWD) and a history of severe and frequent bleeding. The efficacy and safety of prophylaxis with a plasma-derived (pd)VWF/factor VIII (FVIII) concentrate in a 1:1 activity ratio (pdVWF/FVIII 1:1, wilate®) was demonstrated in children (≥6 years) and adults in WIL-31. Limited data exist on VWF prophylaxis in children <6 years. Here, we present results from WIL-33, the first prospective global clinical study assessing pdVWF/FVIII 1:1 prophylaxis in children <6 years with severe VWD. Objectives: The aim of the WIL-33 study was to investigate efficacy, immunogenicity, pharmacokinetics (PK) and safety of 12-months prophylaxis with pdVWF/FVIII 1:1 in children <6 years of age with severe VWD. Methods: WIL-33 (NCT04953884) was an open-label, prospective, non-controlled, global, multicenter phase 3 study investigating pdVWF/FVIII 1:1 prophylaxis in children (<6 years) with severe VWD (defined as VWF ristocetin cofactor activity <20%). pdVWF/FVIII 1:1 was administered 2–3 weekly for 12 months at a recommended dose of 30–50 IU/kg. The primary endpoint was total annualized bleeding rate (TABR) during prophylaxis. Secondary objectives included PK parameters, safety and tolerability. Results: Twelve children (median age 2 years; range 1–5; 50% female) were enrolled and comprised the full analysis set (FAS). The per-protocol robustness (PPR) set, a subset of the FAS, excluded three patients with deviations from recommended dosing. Mean (SD) TABR during prophylaxis in the FAS and PPR set was 4.6 (6.1) and 2.7 (1.8), respectively. Mean (SD) treated TABR was 3.7 (5.1) in the FAS and 2.0 (1.3) in the PPR set. In the PPR set, mean (SD) spontaneous ABR (SABR) was 1.0 (1.3); treated SABR was 0.8 (1.3). ABRs in the PPR set were lower in the second 6 months of prophylaxis compared with first 6 months, with a 54% and 50% reduction in TABR and SABR, respectively (Figure 1). Mean (SD) weekly prophylactic dose was 120.1 (65.0) IU/kg in the FAS and 94.7 (18.5) IU/kg in the PPR set, while the mean (SD) dose per injection was 54.0 (27.5) IU/kg in the FAS and 42.9 (6.5) IU/kg in the PPR set. Most bleeding events (98.2%) during prophylaxis were minor, and all were successfully treated with 1–2 infusions of pdVWF/FVIII 1:1. Almost 40% of all bleeds (FAS: 22/56) were due to allergic rhinitis in one patient (Figure 2). Epistaxis was the most frequent bleed type (FAS: 35/56); only one joint bleed was recorded. PK parameters were within expected ranges with no VWF or FVIII accumulation. No treatment-related serious adverse events, thrombotic events, or treatment-emergent inhibitors were observed. Conclusions: WIL-33 demonstrated that pdVWF/FVIII 1:1 prophylaxis was effective and well tolerated in children aged <6 years with severe VWD. WIL-33 is the first prospective trial specifically investigating prophylaxis in children and supports early, sustained prophylaxis in severe pediatric VWD.
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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.