Presentation Details
| Emicizumab for Severe von Willebrand Disease (VWD) and VWD/hemophilia A: the EmiVWD Study Jonathan Roberts1, 2, MIchael Tarantino1, 2. 1Bleeding & Clotting Disorders Institute, Peoria, IL, USA.2Departments of Pediatrics and Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL, USA |
Abstract
Background: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder, typically characterized by mucocutaneous bleeding, heavy menstrual bleeding, and bleeding with surgical or other hemostatic challenges. There has been increased focus on prophylaxis for VWD with significant bleeding, with currently limited treatment options. Emicizumab is an engineered, monoclonal, bispecific antibody that demonstrates factor VIII-like activity ultimately enhancing thrombin generation, transforming prophylactic therapy for many with in hemophilia A. Anecdotally, emicizumab has been utilized successfully for VWD prophylaxis in a small number of patients, and further investigation is warranted. Furthermore, some individuals have concomitant VWD/hemophilia A, and emicizumab requires investigation in these individuals. Objective: To evaluate if emicizumab is safe and efficacious for prophylaxis in severe VWD and concomitant VWD/hemophilia A. Methods: We initiated a pilot multicenter, prospective open-label study of emicizumab prophylaxis in severe VWD and concomitant VWD/hemophilia A with a target of 40 patients to be enrolled. Participants must be ≥2 years old and will have a one-year retrospective chart review of annualized bleed rate and hemostatic therapies collected at the time of enrollment. Participants will then receive Emicizumab, 3mg/kg weekly for 4 weeks loading dose, followed by once weekly dosing of 1.5mg/kg for a total of 52 weeks total therapy. Per the emicizumab FDA-approved prescribing information for hemophilia A, dose up-titration to 3 mg/kg once weekly will be allowed after 24 weeks on prophylaxis in case of suboptimal efficacy (i.e., ≥ 2 spontaneous and clinically significant bleeds). Treatment records will be maintained along with bleeding event logs. Breakthrough bleeding events may be treated with the patients usual on-demand factor VIII product, with antifibrinolytics or VWF/FVIII concentrates per the investigator’s discretion. Central clinical laboratory testing will be completed, in addition to genetic testing to confirm accurate VWD diagnosis. Analysis will be performed through descriptive statistics to determine proof of principle. Results: We aim to evaluate emicizumab safety and efficacy for prophylaxis in severe VWD and concomitant VWD/hemophilia A and establish bleed occurrence during emicizumab prophylaxis in VWD and concomitant VWD/hemophilia A. Safety of emicizumab in VWD will be evaluated by documenting all adverse events, including hypersensitivity reactions and thrombotic events. Secondary analyses will evaluate treatment burden, bleed occurrence vs that on previous therapy and bleed severity. Two study sites are currently open, in Peoria, IL and Tampa, Florida USA. Eight additional study sites are in process of opening. To date, three adult participants have enrolled on study. Two participants have reported type 3 VWD and one participant has severe type 1 VWD (Table 1) as diagnosed by the participant’s primary clinical hematologist. Study qualifying laboratory values were obtained from historical laboratory values. Conclusions: Prophylaxis in some patients with VWD or concomitant VWD/hemophilia A is important, and this study will shed light on utility of emicizumab prophylaxis in these disorders.
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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.