Trial reportMolecular therapy : the journal of the American Society of Gene Therapy2024
Clinical immunogenicity outcomes from GENEr8-1, a phase 3 study of valoctocogene roxaparvovec, an AAV5-vectored gene therapy for hemophilia A.
Trial report in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed.
- Safety, efficacy, and patient-reported outcomes 6 years after fidanacogene elaparvovec in adults with hemophilia B.Blood advances · 2026Trial
- Durability of efficacy, safety, and quality of life 5 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A: final phase 3 GENEr8-1 trial results.Research and practice in thrombosis and haemostasis · 2026Trial
- Gene therapy for hereditary hematological disorders: From clinical breakthroughs to future horizons.Molecular therapy. Nucleic acids · 2026Review
- Immunogenicity in Approved Adeno-Associated Virus-Based Gene Therapies: A Framework for a Tailored Assessment Strategy.The AAPS journal · 2026Review
- Safety of Adeno-Associated Viral Vectors in Gene Therapy: Mechanisms of Toxicity, Clinical Risks, and Strategies for Their Minimization.International journal of molecular sciences · 2026Review
- Transforming Hemophilia Management: Lessons from Gene Therapy Clinical Trials.Molecular biotechnology · 2026Review
- Hemophilia B gene therapy: a NAb-solute barrier overcome by adeno-associated virus serotype 5.Research and practice in thrombosis and haemostasis · 2026Article
- Immune Response Associated Hepatotoxicity in Hemophilia Gene Therapy: Mechanisms, Management, and Challenges.Journal of hematology · 2026Review
- Assessment of Immune Responses Against AAV Encoded Transgene Products.The AAPS journal · 2026Review
- Etranacogene dezaparvovec in people with hemophilia B with preexisting adeno-associated virus 5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trial.Research and practice in thrombosis and haemostasis · 2026Article
- Unlocking the potential: advancements and applications of gene therapy in severe disorders.Annals of medicine · 2025Review
- Emerging Technologies Tackling Adeno-Associated Viruses (AAV) Immunogenicity in Gene Therapy Applications.Pharmaceutics · 2025Review
- Efficient Scaling up EV-AAVs Production via Cellular Nanoporation for Familial Hypercholesterolaemia Therapy.Journal of extracellular vesicles · 2025Article
- How Close Are We to Achieving Durable and Efficacious Gene Therapy for Hemophilia A and B?Genes · 2025Review
- Natural history of preexisting AAV5 antibodies in adults with hemophilia B during the lead-in of the etranacogene dezaparvovec phase 3 study.Molecular therapy. Methods & clinical development · 2025Article
- Neutralizing Antibodies: Role in Immune Response and Viral Vector Based Gene Therapy.International journal of molecular sciences · 2025Review
- Gene therapy for hemophilia - From basic science to first approvals of "one-and-done" therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Gene regulation technologies for gene and cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Review
- Efficacy, safety, and quality of life 4 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A in the phase 3 GENEr8-1 trial.Research and practice in thrombosis and haemostasis · 2024Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene transfer therapies utilizing adeno-associated virus (AAV) vectors involve a complex drug design with multiple components that may impact immunogenicity. Valoctocogene roxaparvovec is an AAV serotype 5 (AAV5)-vectored gene therapy for the treatment of hemophilia A that encodes a B-domain-deleted human factor VIII (FVIII) protein controlled by a hepatocyte-selective promoter. Following previous results from the first-in-human phase 1/2 clinical trial, we assessed AAV5-capsid- and transgene-derived FVIII-specific immune responses with 2 years of follow-up data from GENEr8-1, a phase 3, single-arm, open-label study in 134 adult men with severe hemophilia A. No FVIII inhibitors were detected following administration of valoctocogene roxaparvovec. Immune responses were predominantly directed toward the AAV5 capsid, with all participants developing durable anti-AAV5 antibodies. Cellular immune responses specific for the AAV5 capsid were detected in most participants by interferon-γ enzyme-linked immunosorbent spot assay 2 weeks following dose administration and declined or reverted to negative over the first 52 weeks. These responses were weakly correlated with alanine aminotransferase elevations and showed no association with changes in FVIII activity. FVIII-specific cellular immune responses were less frequent and more sporadic compared with those specific for AAV5 and showed no association with safety or efficacy parameters.
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