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Presentation Details
| Rurioctocog alfa pegol use in immune tolerance induction: An analysis of a phase 3 study in previously untreated patients with severe hemophilia A Robert F.Sidonio, Jr.1, Flora Peyvandi2, 3, Rachel S.Bercovitz4, Seoh Leng Yeoh5, Zulaiha Muda6, Phu Quoc Le7, Veerle Mondelaers8, Jiaan-Der Wang9, Rashid Kazmi10, Bülent Zülfikar11, Joan Gu12, Srilatha Tangada12. 1Aflac Cancer and Blood Disorders Center, Emory University, Atlanta, GA, USA.2Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy.3Department of Pathophysiology and Transplantation, Universitàdegli Studi di Milano, Milan, Italy.4Department of Pediatrics, Northwestern University Feinberg School of Medicine, and Division of Hematology, Oncology, Neuro-Oncology, and Stem Cell Transplant, Ann & Robert H.Lurie Children's Hospital of Chicago, Chicago, IL, USA.5Department of Pediatrics, Hospital Pulau Pinang, Penang, Malaysia.6Paediatric Department, Hospital Tunku Azizah Women Children Hospital, Kuala Lumpur, Malaysia.7Hémato-Oncologie, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium.8Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent University, Ghent, Belgium.9Center for Rare Disease and Hemophilia, Taichung Veterans General Hospital, Taichung, Taiwan.10University Hospital Southampton, Southampton, United Kingdom.11Department of Paediatric Haematology/Oncology, Istanbul University Oncology Institute, Istanbul, Turkey.12Takeda Development Center Americas, Inc., Cambridge, MA, USA |
Abstract
Background/Objectives: This prespecified analysis of a phase 3 prospective, uncontrolled, open-label study (NCT02615691) evaluates the efficacy and safety of immune tolerance induction (ITI) with rurioctocog alfa pegol (rAHF-PEG) in previously untreated patients (PUPs) aged <6 years with severe hemophilia A and factor VIII (FVIII) inhibitors. Methods: ITI eligibility criteria were high-titer FVIII inhibitors (>5 BU/mL), or low-titer inhibitors (≥0.6 to ≤5.0 BU/mL) that remained uncontrolled despite increased rAHF-PEG dosing and/or bypassing agent use. For ITI, rAHF-PEG was given as low dose (50 IU/kg 3×/week) or high dose (100–200 IU/kg daily) per investigator discretion until ITI success/failure or 33 months had passed: success (inhibitor titer persistently <0.6 BU, FVIII incremental recovery ≥66% baseline and FVIII half-life ≥6 hours); partial success (2 success criteria met at 33 months); failure (no success criteria met at 33 months or <20% inhibitor titer reduction). In this analysis, tolerization was defined as ITI success/partial success. Adverse events (AEs) and serious AEs (SAEs) were reported. All participants/legally authorized representatives gave informed consent. Trial conduct followed the Declaration of Helsinki. Data are reported from the last participant’s last visit (29 Oct 2024). Results: For the 7 participants who received ≥1 rAHF-PEG ITI dose, median (range) exposure days at confirmed inhibitor development was 9 (4–18). Six achieved tolerization: 3 had high-dose ITI (2 with high-titer inhibitors, 1 low) and 3 low dose (1 with high-titer inhibitors, 2 low). One low-dose participant with high-titer inhibitors failed ITI. Median (range) time to the second negative inhibitor titer was 172 (123–188) and 96 (16–616) days for low- and high-dose ITI, respectively. Median (IQR) annualized bleeding rates were 8.9 (8.3) and 1.0 (18.4) for low- and high-dose ITI, respectively. All 7 participants had ≥1 AE (39 total); 4 experienced 12 SAEs overall, of which 1 (development of a FVIII inhibitor before ITI initiation) was treatment related. Two participants had 5 catheter-related AEs, and one had 2 study procedure-related AEs. No thrombotic AEs, hypersensitivity reactions or AEs leading to rAHF-PEG discontinuation were reported. Conclusions: Most participants in this small sample achieved tolerization (86%). Although SAE incidence was high, only one SAE was treatment related, and occurred before ITI initiation. This analysis supports the efficacy and safety of rAHF-PEG as ITI therapy for FVIII inhibitors in PUPs with severe hemophilia A.
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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.