Robert Klamroth, Paul E. Monahan, Paul Van der Valk, Doris Quon, Rashid Kazmi, Michiel Coppens, Niamh O’Connell, Steven W. Pipe, Annette von Drygalski, Saira Afzal, Richard Gabriel, Loubna Youssar, Sean Gill, Nathalie Jansen, Fei Wang, Sandra Le Quellec, Cedric Hermans
Background: Health Outcomes with Padua Gene; Evaluation in Hemophilia B (HOPE-B) is the first phase 3 trial of adeno-associated virus (AAV) serotype 5 vector-based gene therapy for hemophilia B to have enrolled participants with neutralizing antibodies (NAbs) to the viral vector. Objectives: Evaluate the efficacy and safety of etranacogene dezaparvovec in a post hoc subgroup of participants with preexisting AAV5 NAbs 4 years posttherapy. Methods: After a ≥6-month lead-in period on continuous prophylaxis, people with moderately severe/severe hemophilia B (factor [F]IX ≤ 2%) received a single infusion of etranacogene dezaparvovec. AAV5 NAb status prior to infusion was determined. FIX activity, annualized bleeding rates (ABRs), and safety were evaluated in participants with preexisting AAV5 NAbs. Results: < .0001). The most frequent treatment-related adverse events were infusion-related reactions (23.8%) and transient alanine aminotransferase elevations (14.3%). No late hepatotoxicity was observed. Conclusion: Etranacogene dezaparvovec demonstrated long-term efficacy and safety in individuals with preexisting AAV5 NAb titers ≤ 678, expanding eligibility for gene therapy to a broader hemophilia B population.