ArticleNature medicine2012
A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05500807 (Emicizumab for Severe VON Willebrand Disease), which is not on this map. Cited by 220 papers, 3 of them syntheses that pooled it.
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.
Emicizumab for Severe VON Willebrand Disease (VWD) and VWD/Hemophilia A
Who cites it
220 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Emicizumab prophylaxis in people with hemophilia A and inhibitors: a systematic review and meta-analysis.Sao Paulo medical journal = Revista paulista de medicina · 2024Pooled it
- Bispecific Antibodies: From Research to Clinical Application.Frontiers in immunology · 2021Pooled it
- Emicizumab for the treatment of haemophilia A: a narrative review.Blood transfusion = Trasfusione del sangue · 2019Pooled it
- Coagulation potential of concomitant factor VIII administration in people with hemophilia A receiving emicizumab prophylaxis (CAGUYAMA study): a multicenter, open-label, nonrandomized clinical trial.Research and practice in thrombosis and haemostasis · 2026Trial
- Emicizumab dose up-titration in case of suboptimal bleeding control in people with haemophilia A.Haemophilia : the official journal of the World Federation of Hemophilia · 2023Trial
- Effect of emicizumab prophylaxis on bone and joint health markers in people with haemophilia A without factor VIII inhibitors in the HAVEN 3 study.Haemophilia : the official journal of the World Federation of Hemophilia · 2022Trial
- Trial
- Trial
- Trial
- Pharmacokinetics and Pharmacodynamics of Emicizumab in Persons with Hemophilia A with Factor VIII Inhibitors: HAVEN 1 Study.Thrombosis and haemostasis · 2021Trial
- Evaluation of the Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Emicizumab in Healthy Chinese Subjects.Clinical pharmacology in drug development · 2021Trial
- Trial
- Relative and Absolute Bioavailability Study of Emicizumab to Bridge Drug Products and Subcutaneous Injection Sites in Healthy Volunteers.Clinical pharmacology in drug development · 2019Trial
- A Pharmacometric Approach to Substitute for a Conventional Dose-Finding Study in Rare Diseases: Example of Phase III Dose Selection for Emicizumab in Hemophilia A.Clinical pharmacokinetics · 2018Trial
- Trial
- Cost-effectiveness analysis of emicizumab use in hospitalized older individuals with acquired hemophilia A.Blood vessels, thrombosis & hemostasis · 2026Article
- A novel humanized FIX/FX hemophilia A mouse model for preclinical evaluation of FVIIIa-mimetic bispecific antibodies.Blood advances · 2026Article
- Discovery and development of a bispecific antibody for the treatment of hemophilia.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Kunihiro Hattori, Tomoyuki Igawa, and Takehisa Kitazawa share Lasker Award honors for revolutionary hemophilia A therapy.The Journal of clinical investigation · 2026Article
- Maternal-fetal transfer of emicizumab in a pregnant mouse model.Blood advances · 2026Article
160 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
34 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hemophilia A is a bleeding disorder resulting from coagulation factor VIII (FVIII) deficiency. Exogenously provided FVIII effectively reduces bleeding complications in patients with severe hemophilia A. In approximately 30% of such patients, however, the 'foreignness' of the FVIII molecule causes them to develop inhibitory antibodies against FVIII (inhibitors), precluding FVIII treatment in this set of patients. Moreover, the poor pharmacokinetics of FVIII, attributed to low subcutaneous bioavailability and a short half-life of 0.5 d, necessitates frequent intravenous injections. To overcome these drawbacks, we generated a humanized bispecific antibody to factor IXa (FIXa) and factor X (FX), termed hBS23, that places these two factors into spatially appropriate positions and mimics the cofactor function of FVIII. hBS23 exerted coagulation activity in FVIII-deficient plasma, even in the presence of inhibitors, and showed in vivo hemostatic activity in a nonhuman primate model of acquired hemophilia A. Notably, hBS23 had high subcutaneous bioavailability and a 2-week half-life and would not be expected to elicit the development of FVIII-specific inhibitory antibodies, as its molecular structure, and hence antigenicity, differs from that of FVIII. A long-acting, subcutaneously injectable agent that is unaffected by the presence of inhibitors could markedly reduce the burden of care for the treatment of hemophilia A.
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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.