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HTRS2025.P1.1 Safety and efficacy of Mim8 prophylaxis in patients with hemophilia A with or without inhibitors: Results from the phase 3, open-label, randomized controlled FRONTIER2 study
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HTRS2025.P1.1 Safety and efficacy of Mim8 prophylaxis in patients with hemophilia A with or without inhibitors: Results from the phase 3, open-label, randomized controlled FRONTIER2 study

Vlady Ostrow, Chandrakala Shanmukhaiah, Pernille Juul Jørgensen, Johannes Oldenburg, Maria Elisa Mancuso, Tadashi Matsushita, Pratima Chowdary, Steven R. Lentz, Johnny Mahlangu and Ilgiz Rakhmatullin
Research and practice in thrombosis and haemostasis, Vol.9(Supplement 3), 103021
11/2025
DOI: 10.1016/j.rpth.2025.103021
url
https://doi.org/10.1016/j.rpth.2025.103021View
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Abstract

Background: Mim8 (denecimig) is a factor VIIIa mimetic bispecific antibody in clinical development for subcutaneous prophylaxis in hemophilia A (HA). Objectives: Evaluate the efficacy and safety of Mim8 in males and females (aged ≥12 years) with HA with or without inhibitors. Methods: FRONTIER2 (NCT05053139) is a phase 3, open-label, randomized, controlled study. Mim8 was administered using tiered dosing (Fig 1). The aim of this study was to determine the hemostatic effect of Mim8 once-every-week (QW) and once-every-month (QM) at week 26 versus either on demand treatment, or versus previous clotting factor concentrate (CFC) prophylaxis during the run in period. Annualized bleeding rate (ABR) was estimated using a negative binomial regression model. Safety and immunogenicity were evaluated. Study was conducted following informed consent and ethical approval. Results: Overall, 254 patients were randomized either from on-demand treatment into Arms 1, 2a or 2b or from CFC treatment into Arms 3 or 4 (Fig 1). In patients previously treated on-demand, estimated mean ABR [95% CI] for treated bleeds was 0.45 [0.18;1.14] for QW and 0.20 [0.06;0.72] for QM Mim8 prophylaxis, versus 15.75 [10.7;23.2] for continued on-demand treatment (Table 1). Mim8 prophylaxis was superior to on-demand treatment, with ABR reductions of 97.1% (QW) and 98.7% (QM). Comparable reductions in ABRs were observed between patients with and without inhibitors (Table 1). In patients on pre-study CFC prophylaxis, estimated mean ABR for treated bleeds was 2.51 [1.42;4.42] for QW and 1.78 [1.17;2.71] for QM Mim8 prophylaxis, versus 4.83 [3.59;6.51] and 3.10 [2.23;4.29], during run-in CFC prophylaxis, respectively (Table 1). Mim8 prophylaxis was superior to run-in CFC prophylaxis, with ABR reduction of 48.0% (QW) and 42.6% (QM). There were comparable reductions in ABRs observed for patients with non-severe and severe HA (Table 1). Zero bleeds were observed in 65.3–95.0% of patients treated with Mim8 (Table 1). Injection-site reactions occurred in 5.0–12.2% of patients. There were no safety concerns and no clinical evidence of neutralizing anti-Mim8 antibodies. Conclusions: FRONTIER2 demonstrated superiority of Mim8 prophylaxis once-every-week and once-every-month in reducing ABR for treated bleeds compared with either on-demand treatment or clotting factor concentrate prophylaxis. Mim8 was well tolerated, and no safety concerns were observed.

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