Trial reportBlood2021
BAX 335 hemophilia B gene therapy clinical trial results: potential impact of CpG sequences on gene expression.
Trial report in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 125 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Phase 1/2 Open-Label, Single Ascending Dose Trial of a Self-Complementing Optimized Adeno-associated Virus Serotype 8 Factor IX Gene Therapy (AskBio009) in Adults With Hemophilia B
A Prospective, Single-center, Open-arm, Single-arm Study of the Safety and Preliminary Efficacy of Single Intravenous Infusion Administration of LY-M001 Injection in the Treatment of Adult Patients With Gaucher Disease Type I
Who cites it
125 citing papers in PubMed, 3 syntheses or guidelines pooled it, 183 citations in OpenAlex.
- Adeno-associated virus-based gene therapy for hemophilia A and B: a systematic review and meta-analysis.Blood advances · 2024Pooled it
- 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
- rAAV immunogenicity, toxicity, and durability in 255 clinical trials: A meta-analysis.Frontiers in immunology · 2022Pooled it
- Factor IX-Padua AAV gene therapy in hemophilia B: phases 1/2 and 3 trials.Nature medicine · 2026Trial
- Gene therapy for hemophilia B: results from the phase 1/2 101HEMB01/02 studies.Blood advances · 2025Trial
- 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
- Multiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A.The New England journal of medicine · 2021Trial
- Clinical immunogenicity in rAAV gene therapy: Insights and implications.Molecular therapy. Advances · 2026Review
- Factor IX Padua AAV gene therapy in adolescents with hemophilia B: a phase 1 trial.Nature medicine · 2026Article
- Increased gene therapy efficacy through the use of extended half-life clotting factors.Blood advances · 2026Article
- Adeno-Associated Virus Gene Therapy: Is There a Risk of Insertional Mutagenesis?Toxicologic pathology · 2026Review
- Adeno-associated virus-induced neurotoxicity is prevented by CpG depletion.Molecular therapy. Advances · 2026Article
- Consequences of human genetic variations inMolecular therapy. Advances · 2026Article
- Taming immune responses to AAV gene therapy by programmed in vivo Treg expansion.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Deaths in gene therapy of Duchenne muscular dystrophy and other diseases: Underlying mechanisms and mitigating strategies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Phase 1 pilot study for hemophilia-A: AAV8 vector with prophylactic tacrolimus-glucocorticoid achieves therapeutic FVIII activity.Signal transduction and targeted therapy · 2026Article
- Signal Peptide Engineering and Codon Optimization to Enhance α-Gal A Activity for rAAV Gene Therapy of Fabry Disease.Journal of inherited metabolic disease · 2026Article
- Review
- Immune Response Associated Hepatotoxicity in Hemophilia Gene Therapy: Mechanisms, Management, and Challenges.Journal of hematology · 2026Review
- Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
16 authors at 9 institutions in 2 countries.
Funding
Abstract
Gene therapy has the potential to maintain therapeutic blood clotting factor IX (FIX) levels in patients with hemophilia B by delivering a functional human F9 gene into liver cells. This phase 1/2, open-label dose-escalation study investigated BAX 335 (AskBio009, AAV8.sc-TTR-FIXR338Lopt), an adeno-associated virus serotype 8 (AAV8)-based FIX Padua gene therapy, in patients with hemophilia B. This report focuses on 12-month interim analyses of safety, pharmacokinetic variables, effects on FIX activity, and immune responses for dosed participants. Eight adult male participants (aged 20-69 years; range FIX activity, 0.5% to 2.0%) received 1 of 3 BAX 335 IV doses: 2.0 × 1011; 1.0 × 1012; or 3.0 × 1012 vector genomes/kg. Three (37.5%) participants had 4 serious adverse events, all considered unrelated to BAX 335. No serious adverse event led to death. No clinical thrombosis, inhibitors, or other FIX Padua-directed immunity was reported. FIX expression was measurable in 7 of 8 participants; peak FIX activity displayed dose dependence (32.0% to 58.5% in cohort 3). One participant achieved sustained therapeutic FIX activity of ∼20%, without bleeding or replacement therapy, for 4 years; in others, FIX activity was not sustained beyond 5 to 11 weeks. In contrast to some previous studies, corticosteroid treatment did not stabilize FIX activity loss. We hypothesize that the loss of transgene expression could have been caused by stimulation of innate immune responses, including CpG oligodeoxynucleotides introduced into the BAX 335 coding sequence by codon optimization. This trial was registered at www.clinicaltrials.gov as #NCT01687608.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.