ArticleBlood2016
Prophylactic efficacy of BeneFIX vs Alprolix in hemophilia B mice.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- In a nutshell: Explaining joint and muscle bleeding in individuals with haemophilia A and B.British journal of haematology · 2026Review
- Physiologically Based Pharmacokinetic (PBPK) Modeling of FIX in Pediatric Hemophilia B: Extravascular Distribution and Dosing Optimization.Pharmaceutics · 2026Article
- Extravascular factor IX: a semicentennial narrative review.Research and practice in thrombosis and haemostasis · 2026Review
- Extravascular distribution of factor IX-review of experimental and clinical evidence, and relevance for hemophilia B replacement therapy.Research and practice in thrombosis and haemostasis · 2026Review
- Tailored collagen binding of albumin-fused hyperactive coagulation factor IX dictates in vivo distribution and functional properties.Nature communications · 2025Article
- Review
- Modulation of Extravascular Binding of Recombinant Factor IX Impacts the Duration of Efficacy in Mouse Models.Thrombosis and haemostasis · 2023Article
- IDELVION: A Comprehensive Review of Clinical Trial and Real-World Data.Journal of clinical medicine · 2022Review
- International consensus recommendations on the management of people with haemophilia B.Therapeutic advances in hematology · 2022Review
- F9 missense mutations impairing factor IX activation are associated with pleiotropic plasma phenotypes.Journal of thrombosis and haemostasis : JTH · 2022Article
- In silico comparison of pharmacokinetic properties of three extended half-life factor IX concentrates.European journal of clinical pharmacology · 2021Article
- Haemophilia.Nature reviews. Disease primers · 2021Review
- Model-dependent contributions of FXII and FXI to venous thrombosis in mice.Journal of thrombosis and haemostasis : JTH · 2020Article
- Identification of novel glycosylation events on human serum-derived factor IX.Glycoconjugate journal · 2020Article
- Real-world assay variability between laboratories in monitoring of recombinant factor IX Fc fusion protein activity in plasma samples.International journal of laboratory hematology · 2020Article
- Mouse models of hemostasis.Platelets · 2020Review
- Pharmacokinetics in routine haemophilia clinical practice: rationale and modalities-a practical review.Therapeutic advances in hematology · 2020Review
- Hemophilia A and B: molecular and clinical similarities and differences.Haematologica · 2019Review
- Gene-based FVIIa prophylaxis modulates the spontaneous bleeding phenotype of hemophilia A rats.Blood advances · 2019Article
- Defective collagen binding and increased bleeding in a murine model of von Willebrand disease affecting collagen IV binding.Journal of thrombosis and haemostasis : JTH · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
FIX binds tightly to collagen IV. Furthermore, a FIX mutant, FIXK5R, which binds better than wild-type FIX to collagen IV, provides better hemostasis than wild-type FIX, long after both are undetectable in the plasma. There is also credible evidence of extravascular FIX. Here, we use the saphenous vein bleeding model to compare the efficacy of recombinant FIXFc (Alprolix) and wild-type FIX (BeneFIX) in hemophilia B mice 7 days postinfusion. Although the terminal half-life of Alprolix is significantly longer than that of BeneFIX, at equal doses Alprolix is not better at controlling bleeding 7 days postinfusion, presumably because of the extravascular FIX. Both BeneFIX and Alprolix exhibit a linear response in clotting efficacy up to 150 IU/kg, where they appear to saturate an extravascular compartment, because there is no additional prophylactic benefit from higher doses. A robust pool of extravascular FIX is clearly observed surrounding blood vessels, localized to the same region as collagen IV, in 2 representative human tissues: liver and skeletal muscle. We see no increased risk for thrombosis at 250 IU/kg FIX at 6 hours postinfusion. In summary, 7 days postinfusion into hemophilia B mice, BeneFIX and Alprolix are hemostatically indistinguishable despite the latter's increased half-life. We predict that doses of FIX ∼3 times higher than the currently recommended 40 to 50 IU/kg will, because of FIX's large extravascular compartment, efficiently prolong prophylactic hemostasis without thrombotic risk.
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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.