Etranacogene dezaparvovec in people with hemophilia B and without adeno-associated virus serotype 5 neutralizing antibodies: a 4-year subgroup analysis of the Health Outcomes with Padua Gene; Evaluation in Hemophilia B (HOPE-B) trial
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Authors
Raheja P.
O'Connell N.
Verhamme P.
Kampmann P.
Lemons R.S.
Wang F.
Gill S.
Monahan P.E.
Le Quellec S.
Leebeek F.W.G.
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2026
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Article
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Background: In the phase 3 Health Outcomes with Padua Gene; Evaluation in Hemophilia B (HOPE-B) trial, a single dose of etranacogene dezaparvovec was administered to people with severe or moderately severe hemophilia B following a lead-in period (>=6 months) during which they received factor (F)IX prophylaxis. Participants were enrolled regardless of adeno-associated virus serotype 5 (AAV5)-neutralizing antibody (NAb) status at screening. Objective(s): To determine efficacy, pharmacokinetic, and safety outcomes over 4 years postgene therapy in HOPE-B participants who were NAb-negative (NAb-). Method(s): Participants provided serum samples for AAV5 NAb determination using an in vitro AAV5 transduction inhibition assay prior to etranacogene dezaparvovec infusion. Participants who were AAV5 NAb- at this time point were examined in the post hoc subgroup analysis. Result(s): In NAb- participants (N = 33), the mean adjusted annualized bleeding rate was significantly reduced between months 7 and 48 postetranacogene dezaparvovec vs lead-in (0.57 vs 3.80; P < .0001). In years 1 to 4, the annualized bleeding rates were 0.99, 0.72, 0.41, and 0.41, respectively (P < .0001 vs lead-in; N = 33 throughout). The mean (SD) endogenous FIX activity was 40.6 IU/dL (18.6) at month 6 postinfusion (N = 33), remained stable, and was 39.0 IU/dL (16.8) at year 4 (N = 33). Exogenous FIX consumption decreased by 99% during months 7 to 48 vs the lead-in period, and no NAb- participant returned to continuous FIX prophylaxis for 4 years postinfusion. No treatment-related oncogenic events or persistent late hepatotoxicity were observed. Conclusion(s): Etranacogene dezaparvovec proved to be highly effective, superior to FIX prophylaxis for bleeding protection, and safe for 4 years postinfusion in NAb- persons with severe or moderately severe hemophilia B.Copyright © 2026 The Authors
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Research and Practice in Thrombosis and Haemostasis
Volume
10
Issue
1