Wolfgang Miesbach: HOPE-B Challenges 20 Years of Exclusion Criteria
Wolfgang Miesbach, Professor of Medicine at Frankfurt University Hospital, shared on LinkedIn:
”HOPE-B Challenges 20 Years of Exclusion Criteria, Gene Therapy of Haemophilia Works Despite Pre-Existing Immunity.
Etranacogene dezaparvovec is the only product that enrolled patients with detectable anti-AAV5 antibodies (measured by luciferase-based assay) — and crucially, it worked.
The NAb-Positive Cohort (21/54 patients):
- Mean FIX activity: 34 IU/dL at 4 years
- Bleeding reduction: 74%
- Durable response maintained
Antibody titre matters—but only up to a point:
– Titres up to 678 → therapeutic success
– Titre 3,212 → no response
– Direct Comparison with AAV5 Antibody-Negative Patients:
(recently published by Priyanka Raheja et al.) → Outcomes essentially comparable
The Titre Gradient Question:
The paper found no clinically meaningful correlation between baseline AAV5 titre (up to 678) and FIX activity achieved. Antibodies either block completely or they don’t.
Durability:
One NAb+ patient (titre 98.5) had late loss of expression at Month 29.
The Unresolved Grey Zone:
Between titres 678–3,212? We don’t yet know. An ongoing trial should clarify this.
Take-Home Message:
Pre-existing AAV5 antibodies aren’t necessarily a barrier for etranacogene dezaparvovec—at least up to titre 678.
Congratulations to Robert Klamroth and co authors.”
Read the full article in RPTH.
Article: Etranacogene dezaparvovec in hemophilia B participants with pre-existing AAV5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trial
Authors: Robert Klamroth, Paul E. Monahan, Paul Van der Valk, Doris Quon, Rashid Saeed 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
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