CONCIZUMAB PROPHYLAXIS IN PAEDIATRIC PARTICIPANTS WITH HAEMOPHILIA A/B WITH INHIBITORS IN THE PHASE 3 EXPLORER10 STUDY: EFFICACY, SAFETY AND PK/PD RESULTS FROM THE 32-WEEK CUT-OFF

@article{trakymien2026concizumab,
  title = {{CONCIZUMAB PROPHYLAXIS IN PAEDIATRIC PARTICIPANTS WITH HAEMOPHILIA A/B WITH INHIBITORS IN THE PHASE 3 EXPLORER10 STUDY: EFFICACY, SAFETY AND PK/PD RESULTS FROM THE 32-WEEK CUT-OFF}},
  author = {Sonata Šaulytė TRAKYMIEN and Rukhmi BHAT and Anthony Kc CHAN and Anastasios GIAKOUMIS and Victor Jiménez YUSTE and Kaan KAVAKLI and Maria KNUDSEN and Johnny MAHLANGU and Mary MATHIAS and Chiai NAGAE and Salim Mohamed NEKKAL and Nita RADHAKRISHNAN and Allison P WHEELER and Giancarlo CASTAMAN and Vanessa Maira Lima CAMPOS},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107996},
  url = {https://doi.org/10.1016/j.htct.2026.107996},
  note = {CC BY},
}

TY  - JOUR
TI  - CONCIZUMAB PROPHYLAXIS IN PAEDIATRIC PARTICIPANTS WITH HAEMOPHILIA A/B WITH INHIBITORS IN THE PHASE 3 EXPLORER10 STUDY: EFFICACY, SAFETY AND PK/PD RESULTS FROM THE 32-WEEK CUT-OFF
AU  - Sonata Šaulytė TRAKYMIEN
AU  - Rukhmi BHAT
AU  - Anthony Kc CHAN
AU  - Anastasios GIAKOUMIS
AU  - Victor Jiménez YUSTE
AU  - Kaan KAVAKLI
AU  - Maria KNUDSEN
AU  - Johnny MAHLANGU
AU  - Mary MATHIAS
AU  - Chiai NAGAE
AU  - Salim Mohamed NEKKAL
AU  - Nita RADHAKRISHNAN
AU  - Allison P WHEELER
AU  - Giancarlo CASTAMAN
AU  - Vanessa Maira Lima CAMPOS
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107996
UR  - https://doi.org/10.1016/j.htct.2026.107996
AB  - Background: Concizumab is an anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody approved in the US, Europe and other countries for once-daily, subcutaneous prophylaxis for patients aged ≥12 years with haemophilia A/B with or without inhibitors. Aim: To assess concizumab efficacy and safety in paediatric participants with haemophilia A/B with inhibitors (HAwI/HBwI) at the explorer10 (NCT05135559) 32-week cut-off. Methods: Explorer10 is a multi-centre, non-randomised phase 3 study of male paediatric partici-pants (<12 years) who were concizumab-naïve (arm 1) or previously treated with concizumab via compassionate use (arm 2). Concizumab-naïve participants received a 1.0 mg/kg loading dose (Day 1), followed by 0.20 mg/kg daily from Day 2, with potential dose adjustment at 5–8 weeks to 0.15 or 0.25 mg/kg based on plasma concentration. The primary endpoint was the number of treated spontaneous/traumatic bleeding episodes during concizumab prophylaxis vs previous on-demand treatment (≥26 weeks; historical records) in arm 1. Cut-off was when all arm 1 par-ticipants completed week 32 or withdrew. Safety and PK/PD parameters were also evaluated. Informed consent was obtained and the study was approved by local ethics committees. Results: In 24 participants, estimated mean ABR (95% CI) was 2.08 (1.27; 3.41) on concizumab prophylaxis vs 11.51 (7.75; 17.09) with previous on-demand treatment. The ABR ratio was 0.18 (0.11; 0.29; P < 0.001), representing an 82% ABR reduction and demonstrating superiority of con-cizumab prophylaxis. Concizumab plasma concentration remained stable over time, free TFPI levels decreased and remained stable, and the geometric mean thrombin peak increased to within the normal adult range. Concizumab was well tolerated, with no safety concerns identi-fied. Conclusion: In paediatric HAwI/HBwI, concizumab prophylaxis was effective in bleed prevention compared with previous observations.
SN  - 2531-1379
SN  - 2531-1387
ER  -