ArticleThe New England journal of medicine2025
Sustained Clinical Benefit of AAV Gene Therapy in Severe Hemophilia B.
Article in The New England journal of medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00979238 (An Open Label Dose-Escalation Study Of A Self Complementary Adeno-Associated Viral Vector), which is not on this map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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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.
An Open Label Dose-Escalation Study Of A Self Complementary Adeno-Associated Viral Vector (scAAV 2/8-LP1-hFIXco) For Gene Transfer in Hemophilia B
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it.
- [Chinese guidelines on the treatment of hemophilia (2025)].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Guideline
- Gene therapy for hereditary hematological disorders: From clinical breakthroughs to future horizons.Molecular therapy. Nucleic acids · 2026Review
- Once yearly cell-based therapy for sustained and dose-tunable delivery of monoclonal antibodies.Science advances · 2026Article
- A ternary nanocomplex for hepatocyte-targeted gene delivery and treatment of metabolic dysfunction-associated steatotic liver disease.RSC advances · 2026Article
- Personalized Treatment of Hemophilia: Matching Therapies to Patient Needs in a Rapidly Evolving Landscape.Drugs · 2026Review
- Defining the safety and efficacy of liver-directed AAV gene therapy using a human liver tissue-equivalent platform.Molecular therapy. Advances · 2026Article
- Increased gene therapy efficacy through the use of extended half-life clotting factors.Blood advances · 2026Article
- Overview of Patient-Reported Outcomes in Haemophilia Gene Therapy.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2026Review
- Adeno-Associated Virus Gene Therapy: Is There a Risk of Insertional Mutagenesis?Toxicologic pathology · 2026Review
- Expression-linked promoter selection (ELiPS) engineers short, strong ubiquitous promoters for gene therapy applications.bioRxiv : the preprint server for biology · 2026Article
- Reprogramming innate immunity through viral interference: A double-edged strategy for enhancing and containing gene therapies.Molecular therapy. Nucleic acids · 2026Review
- AAV8-mediated mouse/human PROC expression rescues thrombophilia in hereditary protein C-deficient mice.Gene therapy · 2026Article
- Environmental and developmental factors shape anti-AAV immunity in pigs.Gene therapy · 2026Article
- 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
- Six-year FIX-padua gene therapy in hemophilia B.Blood advances · 2026Article
- The poly-(HA-GMA) hydrogel carrying AAV8-sTβRII alleviates scar formation in mice skin wound healing by inhibiting fibrosis.Gene therapy · 2026Article
- Gene Therapy in Hemophilia: Clinical Advances, Immunological Challenges, and Emerging Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Nanozymes for Liver Disease Therapy: Advances in Catalytic Activity, Targeting Strategies, and Clinical Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Hemophilia and hereditary angioedema: parallel therapeutic advances in genetic diseases of serine protease pathways.Research and practice in thrombosis and haemostasis · 2026Review
- Immune Response Associated Hepatotoxicity in Hemophilia Gene Therapy: Mechanisms, Management, and Challenges.Journal of hematology · 2026Review
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28 authors.
Funding
Abstract
backgroundAdeno-associated virus (AAV)-mediated gene therapy has emerged as a promising treatment for hemophilia B. Data on safety and durability from 13 years of follow-up in a cohort of patients who had been successfully treated with scAAV2/8-LP1-hFIXco gene therapy are now available.
methodsTen men with severe hemophilia B received a single intravenous infusion of the scAAV2/8-LP1-hFIXco vector in one of three dose groups (low-dose: 2×10
resultsParticipants were followed for a median of 13.0 years (range, 11.1 to 13.8). Factor IX activity remained stable across the dose cohorts, with mean factor IX levels of 1.7 IU per deciliter in the low-dose group, 2.3 IU per deciliter in the intermediate-dose group, and 4.8 IU per deciliter in the high-dose group. Seven of the 10 participants did not receive prophylaxis. The median annualized bleeding rate decreased from 14.0 episodes (interquartile range, 12.0 to 21.5) to 1.5 episodes (interquartile range, 0.7 to 2.2), which represented a reduction by a factor of 9.7. Use of factor IX concentrate decreased by a factor of 12.4 (interquartile range, 2.2 to 27.1). A total of 15 vector-related adverse events occurred, primarily transient elevations in aminotransferase levels. Factor IX inhibitor, thrombosis, or chronic liver injury did not develop in any participant. Two cancers were identified but were deemed by the investigators, together with an expert multidisciplinary team, as being unrelated to the vector. A liver biopsy that was conducted in 1 participant 10 years after the infusion revealed transcriptionally active transgene expression in hepatocytes without fibrosis or dysplasia. Levels of neutralizing antibodies to AAV8 remained high throughout follow-up, thus indicating potential barriers to readministration of the vector.
conclusionsA single administration of scAAV2/8-LP1-hFIXco gene therapy resulted in durable factor IX expression, sustained clinical benefit, and no late-onset safety concerns over a period of 13 years. These data support the long-term efficacy and safety of AAV gene therapy for severe hemophilia B. (Funded by the U.K. Medical Research Council and others; ClinicalTrials.gov number, NCT00979238; EudraCT number, 2005-005711-17.).
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