Presentation Details
| Recombinant ADAMTS13 prophylaxis in patients with congenital thrombotic thrombocytopenic purpura: interim analysis from the phase 3b continuation study Paul Coppo1, Parth Patwari2, Björn Mellgård2, Hong Li2, Marie Scully3, Masanori Matsumoto4, Jerzy Windyga5, Thomas L Ortel6, Spero Cataland7, Paul Knöbl8, Ziqiang Yu9, Ana Antun10, Sami Ibrahimi11, Doug Criger2, Linda T Wang2. 1APHP.6–Reference Center for Thrombotic Microangiopathies (CNR-MAT), Hôpital St Antoine, Paris, France.2Takeda Development Center Americas, Inc., Cambridge, MA, USA.3University College London Hospitals NHS Foundation Trust, London, United Kingdom.4Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan.5Department of Hemostasis Disorders and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.6Duke University, Durham, NC, USA.7Department of Internal Medicine, Ohio State University, Columbus, OH, USA.8Department of Medicine 1, Division of Hematology and Hemostasis, Medical University of Vienna, Vienna, Austria.9National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.10Department of Hematology and Medical Oncology, School of Medicine, Emory University, Atlanta, GA, USA.11Department of Internal Medicine, Section of Hematology and Oncology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA |
Abstract
Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare, potentially life-threatening disease resulting from severe ADAMTS13 deficiency. Burdensome prophylaxis with plasma infusions can be required to prevent acute TTP and chronic end-organ damage. Long-term prophylaxis with recombinant ADAMTS13 (rADAMTS13; TAK-755; Takeda Development Center Americas, Inc., Lexington, MA, USA) is being investigated in a phase 3b continuation study. Objectives: To evaluate the safety and efficacy of long-term rADAMTS13 prophylaxis in patients with cTTP. Methods: This phase 3b, prospective, open-label, multicenter, continuation study (NCT04683003) enrolled patients with cTTP ages 0 to 70 years. Patients had previously received prophylaxis with rADAMTS13 for 12 months and standard-of-care plasma infusion for 6 months in a randomized, crossover, pivotal trial (NCT03393975; rollover cohort) or had not participated in the pivotal study (non-rollover cohort). Rollover cohort data from a preplanned interim analysis (data cutoff, August 12, 2022) are presented. Patients received intravenous rADAMTS13 40 IU/kg prophylaxis every other week or weekly. The primary outcome was long-term safety and tolerability as assessed by incidence of adverse events (AEs) and serious AEs (SAEs) that were considered related to rADAMTS13. Secondary outcomes included incidences of acute and subacute TTP events and nonacute TTP manifestations. Results: Data from 29 rollover patients were analyzed (mean ± SD age: 40.4 ± 12.1 years; 62% were female). The median (range) duration of rADAMTS13 treatment during the rollover period was 0.7 (0–1.4) years. No acute TTP events occurred during rADAMTS13 prophylaxis, and the incidence rates of subacute TTP events and TTP manifestations were comparable to those with rADAMTS13 prophylaxis in the pivotal study, which was lower than the previous standard of care (Table 1). With approximately 5 months of additional exposure to rADAMTS13 since the interim analysis (February 15, 2023) and data for an additional 7 rollover patients (n=36), there continued to be no related SAEs observed, no treatment interruptions or discontinuation due to AEs (Table 2), and no neutralizing antibodies observed. Conclusions: In the rollover cohort of this continuation study, no adverse drug reactions were identified with rADAMTS13 prophylaxis, and no neutralizing antibodies developed. rADAMTS13 treatment that continued for up to 3.9 years prevented acute TTP events and reduced subacute events and TTP manifestations.
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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.