Prophylactic efficacy of BeneFIX vs Alprolix in hemophilia B mice

Cooley, Brian C.; Funkhouser, William K.; Monroe, Dougald M.; Ezzell, Ashley; Mann, David; Lin, Feng; Monahan, Paul E.; Stafford, Darrel W.

doi:10.1182/blood-2016-01-696104

Cited by 48 publications

(66 citation statements)

References 35 publications

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“…Factor IX is detected in the lymph and in the vascular wall, yet other extravascular compartments may exist. Immunohistochemical evaluation of mouse and human arteries show FIX staining on endothelial cells facing the vessel lumen and in the subendothelial region, where it co‐localizes with collagen IV, a major extracellular component of the endothelial basement membrane . Binding is reversible and mainly involves the Gla‐domain of FIX .…”

Section: Interactions Of Fixmentioning

confidence: 99%

“…For example, in the Phase III trials, an EHL FIX with a larger volume of distribution showed similar haemostatic efficacy during weekly prophylaxis as an EHL FIX with a smaller volume of distribution; this was despite that a 5-fold higher FIX prophylactic dose was used in the study of the former product. [27][28][29] Factor IX is detected in the lymph 30 and in the vascular wall, [31][32][33] yet other extravascular compartments may exist.…”

Section: Extravascular Fix Binding To Collagenmentioning

confidence: 99%

“…show FIX staining on endothelial cells facing the vessel lumen and in the subendothelial region, where it co-localizes with collagen IV, a major extracellular component of the endothelial basement membrane. [31][32][33] Binding is reversible and mainly involves the Gla-domain of FIX. 31,32 Experimental studies in mice have suggested that collagen IV-bound FIX may contribute to haemostasis.…”

Section: Immunohistochemical Evaluation Of Mouse and Human Arteriesmentioning

confidence: 99%

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Phenotypic characterization of haemophilia B – Understanding the underlying biology of coagulation factor IX

Tjärnlund-Wolf

Lassila

2019

Haemophilia

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Haemophilia B is a recessive, X‐linked bleeding disorder due to inherited deficiency in vitamin K‐dependent coagulation factor IX (FIX). FIX activity levels, as a basis for the definition of disease severity, do not clearly correlate with bleeding phenotype, likely due to the multiple steps regulating coagulation. Timely, with the availability of extended half‐life products and successful steps in gene therapy, haemophilia B therapy is in an active developmental phase. Therefore, increased knowledge of the factors contributing to the variation of haemostatic and clinical outcome and response to therapy is welcomed. FIX acts at the crossroads of both the extrinsic and intrinsic pathways, and on the platelet procoagulant membrane at the site of vascular injury, and therefore, FIX biology is targeted for multiple effectors and regulators. The synthesis, cellular and molecular interactions, and elimination routes of FIX are not as well studied as for FVIII. The specific roles of magnesium in both platelet adhesion and FIX activation, and of vascular collagen at the haemostatic site of platelet adhesion and FIX residence are of particular interest. Biochemical and translational research on these issues should improve our understanding of the mechanisms involved, leading to the development of relevant assays that measure both haemostasis and treatment response. The latter is becoming increasingly important in the new era of haemophilia management and ultimately may lead to improved treatment strategies individually tailored to a patient's needs and cost‐efficiency.

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Section: Interactions Of Fixmentioning

confidence: 99%

Section: Extravascular Fix Binding To Collagenmentioning

confidence: 99%

Section: Immunohistochemical Evaluation Of Mouse and Human Arteriesmentioning

confidence: 99%

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Phenotypic characterization of haemophilia B – Understanding the underlying biology of coagulation factor IX

Tjärnlund-Wolf

Lassila

2019

Haemophilia

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“…This is consistent with the recent observations of Cooley et al, that rFIX still provided haemostatic protection 7 days after infusion, in a murine saphenous vein bleeding model, even though no circulating FIX could be measured at that point. These authors and others have therefore suggested that plasma FIX level and terminal half-life may be a poor surrogate marker for haemostatic efficacy in HB [8,9] and distribution half-life of FIX may be clinically more predictive.…”

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confidence: 99%

Weekly recombinant FIX prophylaxis for severe haemophilia B in normal clinical practice: data from UKHCDO and Finland

et al. 2017

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“…They provide evidence that the size of an extravascular pool of FIX bound to collagen IV is the true pharmacodynamic predictor. 1 …”

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confidence: 99%

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Lollar

2016

Blood

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Prophylactic efficacy of BeneFIX vs Alprolix in hemophilia B mice

Abstract: Key Points Because extravascular FIX is physiologically important, FIXs circulating levels do not independently predict hemostatic potential. A saphenous vein hemophilia B mouse model shows that 7 days postinfusion FIX-Fc and FIX provide equal hemostatic protection.

Cited by 48 publications

References 35 publications

Phenotypic characterization of haemophilia B – Understanding the underlying biology of coagulation factor IX

Phenotypic characterization of haemophilia B – Understanding the underlying biology of coagulation factor IX

Weekly recombinant FIX prophylaxis for severe haemophilia B in normal clinical practice: data from UKHCDO and Finland

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