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Presentation Details
| Mim8 Prophylaxis in Adults and Adolescents with Hemophilia A: 52-Week Efficacy and Safety Outcomes from the Phase 3 FRONTIER2 Study Steven R Lentz1, Aby Abraham2, Cihan Ay3, Anthony KC Chan4, Victor Jiménez-Yuste5, Johannes Oldenburg6, Maria Elisa Mancuso7, 8, Johnny Mahlangu9, Tadashi Matsushita10, Lize van Vulpen11, Renchi Yang12, Amalie Rhode Høgh Nielsen13, Ilgiz Rakhmatullin13, Emily Waters14, Pratima Chowdary15, Maria Lage14. 1Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.2Department of Clinical Haematology, Christian Medical College, Vellore, Tamil Nadu, India.3Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.4McMaster Children’s Hospital, McMaster University, Hamilton, ON, Canada.5Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain.6The Institute of Experimental Hematology and Transfusion Medicine, Universitätsklinikum Bonn, Bonn, Germany.7Center for Thrombosis and Hemorrhagic Diseases, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.8Humanitas University, Pieve Emanuele, Milan, Italy.9Department of Molecular Medicine and Haematology, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa.10Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan.11Center for Benign Haematology, Van Creveldkliniek, University Medical Center Utrecht, University Utrecht, Utrecht, Netherlands.12Thrombosis and Hemostasis Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.13Novo Nordisk A/S, Søborg, Denmark.14Novo Nordisk Inc., Plainsboro, NJ, USA.15Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, Department of Haematology, University College London, London, United Kingdom |
Abstract
Background: Mim8 (denecimig) is a new-generation, bispecific antibody, activated factor VIII mimetic in clinical development for subcutaneous prophylaxis (PPX) for hemophilia A (HA), with and without inhibitors. In the phase 3 FRONTIER2 study (NCT05053139), once weekly (QW) and once monthly (QM) Mim8 PPX demonstrated superiority in reducing annualized bleeding rates (ABRs) for treated bleeds versus on-demand therapy or prior clotting factor concentrate (CFC) PPX at 26 weeks. Objectives: Assess efficacy and safety with Mim8 PPX over 52 weeks. Methods: In the 26-week main phase, participants were randomized to Mim8 QW, QM, or continued on-demand standard-of-care treatment and were grouped by prior therapy (on-demand or CFC PPX). In the 26-week extension, on-demand participants switched to Mim8, and others continued their assigned regimens. ABR (primary), safety, and immunogenicity were evaluated. Results: Of 281 participants, 96% completed the extension phase. The pre-study CFC PPX group had more participants with severe HA (86% vs 77%) and fewer participants with inhibitors (2% vs 44%) vs pre-study on-demand group. This analysis includes 27 newly reported participants from China. In the main phase, all participants who continued on-demand treatment (n=18) experienced treated bleeds; estimated mean ABR (95% CI) was 16.09 (11.21;23.09). All entered the extension, where 88% QW (n=7/8) and 70% QM (n=7/10) had zero treated bleeds. ABRs (95% CI) were 0.67 (0.13;3.61) and 0.79 (0.19;3.33), respectively. For previously treated on-demand participants randomized to Mim8, in the QW group, 86% (n=19/22) had zero treated bleeds in the main phase and 91% (n=19/21) in the extension. ABRs (95% CI) were 0.43 (0.17;1.07) and 0.45 (0.19;1.08), respectively. In the QM group, 91% (n=19/21) had zero treated bleeds in the main phase and 86% (n=18/21) in the extension; ABRs (95% CI) were 0.25 (0.08;0.76) and 0.25 (0.08;0.77), respectively. For participants previously on CFC PPX and randomized to Mim8, in the QW group, 67% (n=74/111) had zero treated bleeds in the main phase and 70% (n=73/104) in the extension, with ABRs (95% CI) of 2.32 (1.35;3.99) and 1.28 (0.78;2.08), respectively. In the QM group, 63% (n=69/109) had zero treated bleeds in the main phase and 69% (n=74/108) in the extension; ABRs (95% CI) were 1.79 (1.22;2.63) and 1.54 (0.92;2.59), respectively. AEs occurred in 74% (n=104) of participants receiving Mim8 QW (84% [399/475] of events were mild) and 71% (n=100) receiving QM (82% [321/390] of events were mild). Injection site reactions occurred in 17 (12%) participants receiving QW and 12 (9%) receiving QM Mim8, accounting for 1.81% and 1.34% of injections. Anti-Mim8 antibodies were detected in 21 recipients (7%); all were low/medium titer without evidence of clinical neutralizing activity. No thromboembolic events, hypersensitivity reactions, or clinically relevant laboratory abnormalities were observed. Conclusions: Over 52 weeks, Mim8 QW and QM PPX was well-tolerated and provided sustained bleed protection in adults and adolescents with HA, with or without inhibitors, supporting its use as a long-term PPX option. Previously presented at ASH 2025, Orlando, Florida, 6–9 December 2025.
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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.