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CME Evaluation

Oral Communication Session

Inherited Bleeding Disorders and Inhibitors

Session: Gene therapy - Long term follow up

OC 30.1 - Seven-year follow-up of valoctocogene roxaparvovec gene therapy for haemophilia A

Monday, June 24, 2024
09:30 – 09:45 ICT
Room: Plenary Hall

    Co-Author(s)

  • ES

    Emily Symington

    Consultant Haematologist
    Cambridge University Hospitals NHS Foundation Trust
    Cambridge, England, United Kingdom

  • Savita Rangarajan

    Assoc Professor of Clinical Haematology
    Southampton University Hospital
    Southampton, England, United Kingdom

  • WL

    Will Lester

    Consultant Haematologist
    Univ Hospitals Birmingham NHS Foun Trust
    Birmingham, England, United Kingdom

    • Presenting Author(s)

  • Bella Madan, MD FRCP FRCPath

    Consultant Haematologist
    Guy's & St. Thomas' NHS Foundation Trust
    London, England, United Kingdom

    • Co-Author(s)

  • Glenn F. Pierce, MD PhD

    World Federation of Hemophilia/Consultant
    World Federation of Hemophilia/Consultant
    La Jolla, California, United States

  • Priyanka Raheja

    Consultant Haematologist
    Barts Health NHS Trust
    London, England, United Kingdom

  • Carolyn M. Millar, MD PhD

    Consultant Haematologist
    Imperial College Healthcare NHS Trust & Imperial College London
    London, England, United Kingdom

  • DO

    Dane Osmond

    Associate Director
    BioMarin Pharmaceuticals Inc.
    Novato, California, United States

  • ML

    Mingjin Li

    Associate Director
    BioMarin Pharmaceuticals Inc.
    Novato, California, United States

  • TR

    Tara M. Robinson

    Senior Medical Director
    BioMarin Pharmaceuticals Inc.
    Novato, California, United States

Background: Valoctocogene roxaparvovec is an adeno-associated virus vector serotype 5 (AAV5)-mediated gene therapy approved for severe haemophilia A (HA).

Aims: The aim is to update on seven-year follow-up of valoctocogene roxaparvovec gene therapy for haemophilia A.

Methods: In this open-label, phase 1/2 dose-escalation trial (NCT02576795), males ≥18 years with severe HA (factor VIII [FVIII] ≤1 IU/dL) who were previously receiving exogenous FVIII and had no history of FVIII inhibitors or anti-AAV5 antibodies received an infusion of 6x1013 (n=7) or 4x1013 (n=6) vg/kg valoctocogene roxaparvovec. Efficacy was assessed by FVIII activity (chromogenic assay), bleeding and exogenous FVIII use; safety was assessed with reported adverse events.

Results: At years 7 and 6, median (interquartile range) FVIII activity was 10.3 (4.8–14.2) and 7.2 (4.5–8.9) IU/dL in the 6x1013 (n=5) and 4x1013 (n=4) cohorts, respectively. In the last year, estimated FVIII activity changed by −0.001 and −0.07 IU/dL/week for the 6x1013 and 4x1013 cohorts, respectively. During all follow-up, mean ABRs decreased from BL by 96% and 88% for the 6x1013 and 4x1013 cohorts at years 7 and 6, respectively. A 6x1013 cohort participant resumed prophylaxis after a non–treatment-related grade 4 SAE of spontaneous internal carotid artery bleeding in year 7. Another 6x1013 cohort participant resumed prophylaxis in year 7 following ankle joint bleeds; 6 weeks prior, his FVIII activity was 1.9 IU/dL. A 4x1013 cohort participant transiently returned to prophylaxis during year 5. Mean (median) annualized FVIII infusion rate for the 6x1013 and 4x1013 cohorts were 6.4 (1.6) and 9.3 (5.1) infusions/year over all follow-up, a decline of 95% and 93% from BL, respectively. In the last year, 1 participant in each cohort had a treatment-related AE: grade 1 hepatomegaly (6x1013) and grade 1 splenomegaly (4x1013).

Conclusion(s): While 2 participants resumed prophylaxis in year 7, the majority maintained haemostasis. Safety remains in line with previous reports.