ArticleBlood2012
Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.
- Allometry of factor VIII and informed scaling of next-generation therapeutic proteins.Journal of pharmaceutical sciences · 2013Pooled it
- Trial
- Trial
- Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients.Blood · 2012Trial
- Treatment of canine hemophilia A via intraosseous delivery of a platelet-specific factor VIII-lentiviral vector.Blood vessels, thrombosis & hemostasis · 2026Article
- Article
- Damoctocog Alfa Pegol, a PEGylated B-domain Deleted Recombinant Extended Half-life Factor VIII for the Treatment of Hemophilia A: A Product Review.Drugs in R&D · 2024Review
- Factor VIII moiety of recombinant Factor VIII Fc fusion protein impacts Fc effector function and CD16Frontiers in immunology · 2024Article
- Coagulation factor VIII regulates von Willebrand factor homeostasis invivo.Journal of thrombosis and haemostasis : JTH · 2023Article
- Chloroplast transformation for bioencapsulation and oral delivery using the immunoglobulin G fragment crystallizable (Fc) domain.Scientific reports · 2023Article
- Pharmacokinetic analysis identifies a factor VIII immunogenicity threshold after AAV gene therapy in hemophilia A mice.Blood advances · 2022Article
- The Instability of Dimeric Fc-Fusions Expressed in Plants Can Be Solved by Monomeric Fc Technology.Frontiers in plant science · 2021Article
- Purification of Modified Therapeutic Proteins Available on the Market: An Analysis of Chromatography-Based Strategies.Frontiers in bioengineering and biotechnology · 2021Review
- Factor VIII-Fc Activates Natural Killer CellsFrontiers in immunology · 2021Article
- Treatment of Hemophilia A Using Factor VIII Messenger RNA Lipid Nanoparticles.Molecular therapy. Nucleic acids · 2020Article
- FVIII half-life extension by coadministration of a D'D3 albumin fusion protein in mice, rabbits, rats, and monkeys.Blood advances · 2020Article
- Article
- Immunogenicity Risk Assessment for an Engineered Human Cytokine Analogue Expressed in Different Cell Substrates.The AAPS journal · 2020Review
- Hemophilia therapy: the future has begun.Haematologica · 2020Review
- Factor VIII Fc Fusion Protein but not FVIII Drives Human Monocyte-Derived Dendritic Cell Activation via FcγRIIa.HemaSphere · 2020Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Despite proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of factor VIII. A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed to determine the potential for reduced frequency of dosing. rFVIIIFc has an ∼ 2-fold longer half-life than rFVIII in hemophilia A (HemA) mice and dogs. The extension of rFVIIIFc half-life requires interaction of Fc with the neonatal Fc receptor (FcRn). In FcRn knockout mice, the extension of rFVIIIFc half-life is abrogated, and is restored in human FcRn transgenic mice. The Fc fusion has no impact on FVIII-specific activity. rFVIIIFc has comparable acute efficacy as rFVIII in treating tail clip injury in HemA mice, and fully corrects whole blood clotting time (WBCT) in HemA dogs immediately after dosing. Furthermore, consistent with prolonged half-life, rFVIIIFc shows 2-fold longer prophylactic efficacy in protecting HemA mice from tail vein transection bleeding induced 24-48 hours after dosing. In HemA dogs, rFVIIIFc also sustains partial correction of WBCT 1.5- to 2-fold longer than rFVIII. rFVIIIFc was well tolerated in both species. Thus, the rescue of FVIII by Fc fusion to provide prolonged protection presents a novel pathway for FVIII catabolism, and warrants further investigation.
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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.