ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Early Phase Clinical Immunogenicity of Valoctocogene Roxaparvovec, an AAV5-Mediated Gene Therapy for Hemophilia A.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 3 of them syntheses that pooled it.
What it found
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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
47 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Adeno-associated virus-based gene therapy for hemophilia A and B: a systematic review and meta-analysis.Blood advances · 2024Pooled it
- Liver-related aspects of valoctocogene roxaparvovec gene therapy for hemophilia A: expert guidance for clinical practice.Blood advances · 2024Guideline
- A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Pooled it
- A phase 1/2 safety and efficacy study of TAK-754 gene therapy: The challenge of achieving durable factor VIII expression in haemophilia A clinical trials.Haemophilia : the official journal of the World Federation of Hemophilia · 2025Trial
- Clinical immunogenicity outcomes from GENEr8-1, a phase 3 study of valoctocogene roxaparvovec, an AAV5-vectored gene therapy for hemophilia A.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Trial
- Immunogenicity in Approved Adeno-Associated Virus-Based Gene Therapies: A Framework for a Tailored Assessment Strategy.The AAPS journal · 2026Review
- Assessment of Immune Responses Against AAV Encoded Transgene Products.The AAPS journal · 2026Review
- Enhancing AAV9-UFμDys1 Gene Therapy Efficacy Through Immunosuppression in Mice with Pre-Existing Immunity and Enabling Redosing Strategies for Duchenne Muscular Dystrophy.Human gene therapy · 2026Article
- Exploring AAV-Mediated Gene Therapy for Inner Ear Diseases: from Preclinical Success to Clinical Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Use of CD19-targeted immune modulation to eradicate AAV-neutralizing antibodies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Distinct infectivity and neutralization antibody responses in the highly homologous AAV Go.1 and AAV5.Frontiers in medicine · 2025Article
- Immunogenicity risk assessment of empty capsids present in adeno-associated viral vectors using predictive innate immune responses.Journal of pharmaceutical sciences · 2024Article
- Optimizing liver health before and after gene therapy for hemophilia A.Blood advances · 2024Review
- Roctavian gene therapy for hemophilia A.Blood advances · 2024Review
- [A recombinant adeno-associated virus expressing secretory TGF-β type Ⅱ receptor inhibits triple-negative murine breast cancer 4T1 cell proliferation and lung metastasis in mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Multicenter assessment and longitudinal study of the prevalence of antibodies and related adaptive immune responses to AAV in adult males with hemophilia.Gene therapy · 2024Article
- Article
- Understanding AAV vector immunogenicity: from particle to patient.Theranostics · 2024Review
- Iron oxide-coupled CRISPR-nCas9-based genome editing assessment in mucopolysaccharidosis IVA mice.Molecular therapy. Methods & clinical development · 2023Article
- Suitable Disinfectants with Proven Efficacy for Genetically Modified Viruses and Viral Vectors.Viruses · 2023Review
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evaluation of immune responses to adeno-associated virus (AAV)-mediated gene therapies prior to and following dose administration plays a key role in determining therapeutic safety and efficacy. This report describes up to 3 years of immunogenicity data following administration of valoctocogene roxaparvovec (BMN 270), an AAV5-mediated gene therapy encoding human B domain-deleted FVIII (hFVIII-SQ) in a phase 1/2 clinical study of adult males with severe hemophilia A. Patients with pre-existing humoral immunity to AAV5 or with a history of FVIII inhibitors were excluded from the trial. Blood plasma and peripheral blood mononuclear cell (PBMC) samples were collected at regular intervals following dose administration for assessment of humoral and cellular immune responses to both the AAV5 vector and transgene-expressed hFVIII-SQ. The predominant immune response elicited by BMN 270 administration was largely limited to the development of antibodies against the AAV5 capsid that were cross-reactive with other common AAV serotypes. No FVIII inhibitor responses were observed within 3 years following dose administration. In a context of prophylactic or on-demand corticosteroid immunosuppression given after vector infusion, AAV5 and hFVIII-SQ peptide-specific cellular immune responses were intermittently detected by an interferon (IFN)-γ and tumor necrosis factor (TNF)-α FluoroSpot assay, but they were not clearly associated with detrimental safety events or changes in efficacy measures.
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