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Presentation Details
| FRONTIER5 direct switch study: Safety of initiating Mim8 prophylaxis without washout of emicizumab Johannes Oldenburg1, Gary Benson2, Pratima Chowdary3, Robert Klamroth1, 4, Anne Lienhart5, Davide Matino6, Camila Martins Mazini Tavares7, Keiji Nogami8, Flora Peyvandi9, 10, Amalie Rhode Høgh Nielsen7, Guy Young11, Emily Waters12, Allison P Wheeler13, Atish Patel12. 1Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Bonn, Germany.2Department of Haematology, Belfast Health and Social Care Trust, Belfast, United Kingdom.3Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, United Kingdom.4Vivantes Klinikum im Friedrichshain, Berlin, Germany.5Unite d'Hemostase Clinique, Centre de Reference de l'Hemophilie, Hopital Louis Pradel, Lyon, France.6Department of Medicine, McMaster University, Hamilton, ON, Canada.7Novo Nordisk A/S, Søborg, Denmark.8Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.9Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122, Milan, Italy.10Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.11Cancer and Blood Disease Institute, Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.12Novo Nordisk Inc., Plainsboro, NJ, USA.13Washington Center for Bleeding Disorders, Seattle, WA, USA |
Abstract
Background: Mim8 (denecimig) is an activated factor VIII mimetic, fully human, bispecific IgG4 antibody in development for prophylaxis in patients with hemophilia A (HA) with/without inhibitors. Efficacy and safety of once-every-week (QW) and once-every-month (QM) Mim8 prophylaxis were investigated in the Phase 3 FRONTIER2 and FRONTIER3 trials, and once-every-two-weeks (Q2W) Mim8 in FRONTIER4. FRONTIER5 (NCT05878938) is a single-arm, open-label, 26-week, Phase 3b study during which patients previously receiving emicizumab were switched directly to Mim8 without a washout period. Objectives: To evaluate the safety of Mim8 prophylaxis in adults and adolescents with HA with/without inhibitors following a direct switch from emicizumab treatment without a washout period nor Mim8 loading dose. Methods: Mim8 was administered subcutaneously by a pen injector QW, Q2W, or QM for 26 weeks via a weight-based tiered-dosing approach; no Mim8 loading dose was administered. Mim8 treatment frequency was chosen based on patient preference and discussion with the investigator, which may have varied from the patient’s previous emicizumab dosing frequency (QW, Q2W, or once-every-four-weeks [Q4W]). The first Mim8 maintenance dose was administered on the planned emicizumab dosing day. Males/females aged ≥12 years with HA (any severity) who previously received emicizumab prophylaxis for ≥8 weeks prior to screening were included. The primary endpoint was to evaluate the number of treatment-emergent adverse events (TEAEs). The study was conducted with informed consent and institutional ethical approval. Results: Sixty-one patients were exposed to Mim8 and completed 26 weeks of treatment (Table 1). Total exposure time: 30.8 years; 107 TEAEs were observed in 43 (70.5%) patients (3.5 TEAEs/patient-years of exposure); most were mild/moderate (88.6%; Table 2). Four serious TEAEs were reported in 4 (6.6%) patients, all unlikely to be related to Mim8. Eighteen (29.5%) patients reported 24 TEAEs that were possibly/probably related to Mim8. Injection site reactions were reported by 12 (19.7%) patients in 15/990 (1.5%) total injections (most transient; all mild). No thromboembolic events, hypersensitivity reactions, or TEAEs leading to discontinuation were observed. There was no measured clinical evidence of neutralizing anti-Mim8 antibodies. Steady-state Mim8 concentration was achieved by Week 16; emicizumab elimination was completed by Week 26. No exaggerated thrombin peak height response was observed. Conclusions: A direct switch from emicizumab to Mim8 prophylaxis treatment, without a washout period, in adolescents and adults with HA with/without inhibitors was well tolerated, and no safety concerns were observed. Previously presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress, Washington, DC, USA, 21-25 June 2025.
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