{
  "abstract": "Background: Mim8 (denecimig) is a next-generation, FVIIIa mimetic intended for subcutaneous prophylaxis of haemophilia A with or without FVIII inhibitors (HAwI/HA). Previous FRONTIER studies found Mim8 efficacious, well-tolerated, and without safety concerns. Aims: Investigate long-term safety and efficacy across Mim8 dosing frequencies in adolescents and adults with HAwI/HA. Methods: Ongoing FRONTIER4 (NCT05685238) enrolled participants from completed Mim8 phase-2/3 studies. Participants aged ≥12 years received Mim8 once-every-week (QW), once-every-two-weeks (Q2W) or once-every-month (QM). Primary endpoints were number of adverse events (AEs), serious AEs, and unintended medical events. Secondary endpoints included injec-tion site reactions (ISRs), anti-Mim8 antibodies, treated bleeding episodes, and annualised bleeding rates (ABRs). Bleeds were analysed using a negative binomial regression model. The study followed Good Clinical Practice and the Declaration of Helsinki, was approved by local eth-ics committees, and participants provided written informed consent. Results: Of 365 participants, 24.4% were aged 12-17 years, 11% had HAwI, and 87.1% severe haemophilia. Mean (SD) age was 33 (16) years and 98.6% were male. Participants entered FRON-TIER4 with a 12-month median ABR of 0.58 and mean (SD) Mim8 exposure of 1.17 (0.30) years. Over mean (SD) treatment analysis period of 0.57 years, no thromboembolic events were re-ported (Table 1). Of the serious AEs, 1 fatal outcome was unlikely related to Mim8. Of 6138 injec-tions, 1.8% resulted in ISRs and 0.4% in pain and/or burning. All ISRs were mild and transient. Anti-Mim8 antibody incidence was 4.7% with no clinical evidence of neutralising effect. Across QW, Q2W and QM, estimated mean ABRs (95%CI) were 0.91 (0.66-1.27), 0.55 (0.34-0.87) and 0.74 (0.54-1.02), respectively, and participants with zero treated-bleed rates (95%CI) were 70.4% (61.9-77.9), 80.8% (71.7-88.0), and 70.9% (63.5-77.5), respectively. ABRs across bleed subtypes were low, and most participants had zero treated bleeds (Figure 1). ABRs (95%CI) for HA and HAwI participants were 0.88 (0.71-1.08) and 0.15 (0.05-0.45), respectively, across dosing frequencies. Conclusion: Interim analyses from FRONTIER4 supports long-term safety and efficacy of Mim8 prophylaxis in adults and adolescents with consistently low ABRs across dosing frequen-cies and inhibitor status.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Hematology and Transfusion Medicine, Poland",
    "Novo Nordisk, Spain",
    "University Clinic Bon, Germany",
    "IRCCS Humanitas Research Hospital, Italy",
    "McMaster University, Canada",
    "Novo Nordisk, Denmark",
    "Nagoya University Hospital, Japan",
    "Novo Nordisk, Rio de Janeiro, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jerzy WINDYGA"
    },
    {
      "affs": [
        1
      ],
      "name": "Llenalia María García FERNÁNDEZ"
    },
    {
      "affs": [
        2
      ],
      "name": "Johannes OLDENBURG"
    },
    {
      "affs": [
        3
      ],
      "name": "Maria Elisa MANCUSO"
    },
    {
      "affs": [
        4
      ],
      "name": "Davide MATINO"
    },
    {
      "affs": [
        5
      ],
      "name": "Ilgiz RAKHMATULLIN"
    },
    {
      "affs": [
        6
      ],
      "name": "Tadashi MATSUSHITA"
    },
    {
      "affs": [
        7
      ],
      "name": "Vanessa Maira Lima CAMPOS"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9tzwh193pr92e.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.108030",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926017773",
  "id": "9tzwh193pr92e",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.108030",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2720|Hemophilia Treatment and Research"
    ]
  ],
  "openalex": "W7223098112",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/9tzwh193pr92e.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:31Z",
      "native_id": "3bece315802f41c7ae37f556278623c9",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.108030"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC633-647.5",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "MIM8 PROPHYLAXIS IN ADULTS AND ADOLESCENTS WITH HAEMOPHILIA A WITH OR WITHOUT INHIBITORS: IN-TERIM RESULTS FROM THE FRONTIER4 LONG-TERM SAFETY AND EFFICACY STUDY",
  "title_text": "MIM8 PROPHYLAXIS IN ADULTS AND ADOLESCENTS WITH HAEMOPHILIA A WITH OR WITHOUT INHIBITORS: IN-TERIM RESULTS FROM THE FRONTIER4 LONG-TERM SAFETY AND EFFICACY STUDY",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:31Z",
  "url": "https://research.draconitic.com/paper/9tzwh193pr92e",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}