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Presentation Details
| FRONTIER3: Safety and efficacy of Mim8 prophylaxis in pediatric patients with hemophilia A Johnny Mahlangu1, M.Elaine Eyster2, Karin Fijn van Draat3, Gili Kenet4, Nita Radhakrishnan5, Irena Woznica-Karczmarz6, Runhui Wu7, Chur Woo You8, Andrea Paramo Florencio9, Jay Jay Thaung Zaw9, Emily Waters10, Manuel Carcao11, Niki Patel10. 1Department of Molecular Medicine and Haematology, University of the Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa.2Department of Medicine, Penn State College of Medicine, Hershey, PA, USA.3Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Pediatric Hematology, Amsterdam, Netherlands.4National Hemophilia Center, Sheba Medical Center, Tel HaShomer, Israel.5Department of Pediatric Hematology Oncology, Post Graduate Institute of Child Health, Noida, India.6Department of Transfusion Medicine, Children`s University Hospital, Lublin, Poland.7Department of Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.8Daejeon Eulji Medical Center, Eulji University, Daejeon, Korea.9Novo Nordisk A/S, Søborg, Denmark.10Novo Nordisk, Inc., Plainsboro, NJ, USA.11Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada |
Abstract
Background: Mim8 (denecimig) is a factor VIII mimetic bispecific antibody in clinical development for subcutaneous (SC) prophylaxis in hemophilia A (HA) with inhibitors (HAwI) or without. This interim analysis reports results from the phase 3, open-label FRONTIER3 pediatric study (NCT05306418) when all patients completed Part 1. Objectives: To evaluate the safety and efficacy of Mim8 prophylaxis in pediatric patients with hemophilia A, with or without inhibitors, based on results from Parts 1 and 2 of the FRONTIER3 study. Methods: FRONTIER3 enrolled patients with HA/HAwI (aged 1–11 years) of any severity to receive 26 weeks of SC Mim8 once weekly (QW) in Part 1 (completed), then the option of 26 weeks of Mim8 QW or once monthly (QM) in Part 2 (ongoing). The study included a run-in period of at least 26 weeks for patients previously treated with prophylaxis. Primary endpoint was the number of TEAEs. Secondary endpoints included number of treated bleeds, bleed subtypes, anti-drug antibodies (ADAs), injection site reactions (ISRs) and Mim8 plasma concentration. Results: In total, 70 patients (n=36 aged 1–5 years; n=34 aged 6–11 years) enrolled in and completed Part 1; most (n=60, 85.7%) had severe HA (n=8 [11.4%] had moderate, n=2 [2.9%] had mild); 14 (20%) had HAwI. In Part 2, 38 patients continued Mim8 QW, and 31 switched to Mim8 QM. 198 TEAEs were reported in 58 (82.9%) patients across Part 1 and 2 (total exposure time [TET]: 59.6 years). No TEAEs were severe, and no hypersensitivity reactions or TEAEs of special interest (including thromboembolic events such as thrombotic microangiopathy) were reported. ISRs occurred in 6 (8.6%) patients; 0.97% of injections led to ISRs. No evidence of neutralizing ADAs was observed. In Part 1, estimated mean annualized bleeding rate (ABR; negative binomial model) for treated bleeds with Mim8 QW was 0.53 (95% CI: 0.30;0.94); median observed ABR was 0.00; TET was 35.4 years; 74.3% of patients had zero treated bleeds. In Part 2, estimated mean ABR for treated bleeds was 0.37 (95% CI: 0.15;0.90) for Mim8 QW and 0.21 (0.05;0.85) for Mim8 QM; median ABR was 0.00 in both groups; TET was 14.7 and 9.5 years; and 86.8% and 93.5% of patients had zero treated bleeds, respectively. Among patients with HAwI (n=14), none reported treated bleeds across Part 1 and 2. Mim8 plasma concentration was within the expected range. Conclusions: Mim8 QW and QM prophylaxis was well tolerated in pediatric patients with HA/HAwI. No safety concerns were observed. Mim8 QW was shown to be efficacious in FRONTIER3. Previously presented at the 18th Annual European Association for Haemophilia and Allied Disorders (EAHAD) Congress, Milan, Italy, 4–7 February 2025.
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