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    Poster Networking

    Hemophilia and Rare Bleeding Disorders

    Poster Networking Session

    PB0623 - An enriched population pharmacokinetic model for recombinant factor IX-Fc fusion including young children with haemophilia B

    Monday, June 26, 2023
    18:30 – 19:30 ET
    Room: Exhibition

      Co-Author(s)

    • Sjoerd F. Koopman, MSc.

      PhD-candidate
      Hospital Pharmacy-Clinical Pharmacology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
      Amsterdam, Noord-Holland, Netherlands

      • Co-Author(s)

    • TG

      Tine M.H.J. Goedhart

      PhD-candidate
      Department of Pediatric Hematology and Oncology, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
      Rotterdam, Zuid-Holland, Netherlands

    • LB

      Laura H. Bukkems

      PhD
      Hospital Pharmacy-Clinical Pharmacology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
      Amsterdam, Noord-Holland, Netherlands

    • Frank W.G. Leebeek, MD, PhD

      Professor and Head of Department of Hematology
      Erasmus MC, University Medical Center Rotterdam, The Netherlands
      Rotterdam, Zuid-Holland, Netherlands

    • KF

      Karin Fijnvandraat

      Professor
      Amsterdam UMC, University of Amsterdam, Emma Children’s Hospital, Pediatric Hematology Amsterdam, Netherlands
      Amsterdam, Noord-Holland, Netherlands

    • Michiel Coppens, MD, PhD (he/him/his)

      Medical Specialist
      Amsterdam University Medical Centers, Amsterdam, The Netherlands
      Amsterdam, Noord-Holland, Netherlands

    • MM

      Mary Mathias

      Dr
      Haemophilia Comprehensive Care Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
      London, England, United Kingdom

    • Peter W. Collins, MD

      Professor of Haematology
      Arthur Bloom Haemophilia Centre, School of Medicine, Cardiff University Hospital, Cardiff, United Kingdom
      Cardiff, Wales, United Kingdom

    • RT

      Robert C. Tait

      Dr, Honorary Professor
      Department of Haematology, Royal Infirmary, Glasgow, United Kingdom
      Glasgow, Scotland, United Kingdom

    • Nicola Curry, MD, FRCP, FRCPath

      Associate Professor
      Oxford University Hospitals NHS Foundation Trust
      Oxford, England, United Kingdom

    • JP

      Jaenette Payne

      Dr, Consultant Haematologist
      Department of Paediatric Haematology, Sheffield Children’s NHS Foundation Trust, Sheffield, United Kingdom
      Sheffield, England, United Kingdom

    • PC

      Pratima Chowdary, MD

      Consultant Haematologist
      Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free London NHS Foundation Trust, London, United Kingdom
      London, England, United Kingdom

    • RM

      Ron A.A. Mathôt

      Professor, PhD
      Hospital Pharmacy-Clinical Pharmacology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
      Amsterdam, Noord-Holland, Netherlands

    • MC

      Marjon H. Cnossen

      Associate professor, pediatric hematologist, MD, PhD
      Department of Pediatric Hematology, Erasmus MC – Sophia Children’s Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
      Rotterdam, Zuid-Holland, Netherlands

      • Presenting Author(s)

    • Caroline Mussert, MD

      PhD student
      Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam
      Rotterdam, Zuid-Holland, Netherlands

    Background: Recombinant factor IX Fc fusion protein (rFIX-Fc) is an extended half-life (EHL)-clotting factor concentrate used in haemophilia B. Previously, a rFIX-Fc three-compartment population pharmacokinetic (PopPK) model was developed, using data from 124 adults and 11 children of ≥12 and < 18 years of age. However, children < 12 years of age are treated with rFIX-Fc as well. Moreover, this model has not been externally validated.

    Aims: Assess the predictive performance of the published rFIX-Fc and develop a PopPK model that describes the PK of patients of all ages.

    Methods: We collected data from haemophilia patients (FIX activity level ≤ 5 IU/dL) treated with rFIX-Fc and included in the OPTI-CLOT TARGET study (NTR7523) and United Kingdom (UK)-EHL registry (NCT02938156). Predictive performance was assessed by comparing observed FIX levels with predicted FIX levels by calculating mean percentage error (MPE, bias) and mean absolute percentage error (MAPE, inaccuracy). The enriched population PK model was constructed using nonlinear mixed-effects modelling (NONMEM).

    Results: We included 37 patients (median age: 16.0 years, range 2.3-73.3) of whom 12 patients < 12 years of age. Observed levels were significantly higher than levels predicted by the published model. The new enriched two-compartment model adequately described the observed clinical data. Age had a significant effect on clearance (CL) and was included as covariate. The enriched model shows improved characterization of FIX activity (Figure 1). MPE was -36.3% (95% CI: -48.1 to -24.4%) and 23.2% (95% CI: 2.98 to 43.4%) for the published and enriched model, respectively, whereas MAPE was 23.3% (95% CI: -10.5 to 57.1%) and 17.0% (95% CI: -6.61 to 40.1).

    Conclusion(s): Population PK parameters derived from our enriched model differ considerably from those reported earlier. The enriched model better describes the PK for children < 12 years of age underlining the necessity to strive for representative PopPK models.