Highlights From the 18th Annual Congress of the European Association for Haemophilia and Allied Disorders 2025
Natural history of AAV5 neutralizing antibodies in adults with haemophilia B during ≥ 6-month screening and lead-in to the HOPE-B trial with etranacogene dezaparvovec gene therapy
Presenting Author: Robert Klamroth, MD
R. Klamroth1, M. Recht2, N. Key3, W. Miesbach4, S. W. Pipe5, P. van der Valk6, R. Kaczmarek7, D. Drelich8, N. Galante8, S. LeQuellec9, P. E. Monahan8, B. Salazar8, J. M. Tarrant8
- Vivantes Klinikum, Berlin, Germany
- Yale University School of Medicine, New Haven, CT
- UNC Blood Research Center and Department of Medicine, Chapel Hill, NC, United States
- University Hospital Frankfurt, Frankfurt, Germany
- University of Michigan, Ann Arbor, MI, United States
- Center for Benign Haematology, Thrombosis and Haemostasis, University Medical Center Utrecht, University Utrecht, Van Creveldkliniek, Utrecht, Netherlands
- IU School of Medicine, Indianapolis, IN
- CSL Behring, King of Prussia, PA, United States
- CSL Behring Europe, Hattersheim am Main, Germany
Overview
This study characterized changes in neutralizing antibodies (NAbs), as well as immunoglobulin (Ig) G and IgM anti-AAV5 binding antibodies, over a lead-in period of at least six months in adult males with hemophilia B (factor IX ≤ 2%). 67 participants were screened and monitored approximately every 1–2 months using AAV5 antibody assays, including a final baseline visit before gene therapy infusion. AAV5 NAbs were assessed using a cell-based luminescence reporter assay, while IgG and IgM anti-AAV5 subclasses were measured via ELISA.
Results from the HOPE-B trial demonstrated that AAV5 NAb levels were relatively stable over a median lead-in period of 240 days, with seroconversion being rare and no observed impact on liver transduction or FIX expression. Although AAV5 NAbs and AAV5 IgG levels were correlated, NAb titers were generally lower. Given the potential influence of preexisting AAV5 NAbs on gene therapy outcomes, patients should be assessed for NAb titers before receiving etranacogene dezaparvovec.
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