Nonacog gamma, a novel recombinant factor IX with low factor IXa content for treatment and prophylaxis of bleeding episodes

2015 ◽  
Vol 8 (2) ◽  
pp. 163-177 ◽  
Author(s):  
Peter L Turecek ◽  
Brigitt Abbühl ◽  
Srilatha D Tangada ◽  
Miranda Chapman ◽  
Herbert Gritsch ◽  
...  
Keyword(s):  
Factor Ix ◽  
Factor Ixa ◽  
Recombinant Factor Ix ◽  
Bleeding Episodes

Nonacog Alpha - an Efficient Therapeutic Option in Hemostase Management for Hemophilia Type B in Patients with Elective Arthropalsties

2018 ◽  
Vol 69 (7) ◽  
pp. 1911-1914
Author(s):  
Oana Viola Badulescu ◽  
Razvan Tudor ◽  
Wilhelm Friedl ◽  
Manuela Ciocoiu ◽  
Paul Dan Sirbu
Keyword(s):  
Therapeutic Option ◽  
Coagulation Factors ◽  
Factor Ix ◽  
Joint Disease ◽  
Type B ◽  
Total Endoprosthesis ◽  
Recombinant Factor Ix ◽  
Bleeding Episodes ◽  
Low Incidence ◽  
Articular Pathology

Hemophilia is a hereditary coagulopathy that is largely in the attention of developing countries, not because of its low incidence, but because of the high costs involved in the treatment of the disease and its disabling consequences of the disease, if treated inappropriately. The concentrates of coagulation factors currently available for the substitution treatment of hemophilic patients have undergone additional viral purification and inactivation techniques, in order to achieve a higher infectious safety, an aspect that also implies an increase in treatment costs for these patients. Currently, the major morbidity of patients with hemophilia is represented by the disabling articular pathology, secondary to repetitive bleeding episodes developed in the articular space. Although it has been proved that the prophylactic administration of coagulation factors helps to prevent joint disease in the case of patients that were not subject to prophylaxis, the repeated bleeding in the joints induces synovitis, which is irreversible and may progress despite subsequent prophylaxis. Under these conditions, total joint arthroplasty remains the only solution to reduce both, pain and subsequent bleeding episodes of hemophilic arthropathy. Effective hemostasis is a basic condition for successful interventions in hemophilic patients. In this regard, this paper aims to highlight the effectiveness of Nonacog Alpha, a product that contains recombinant factor IX, in the management of hemostasis, in the case of a patient with type B hemophilia, with indication of total endoprosthesis of the left hip.

scholarly journals Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B

2017 ◽  
Vol 117 (03) ◽  
pp. 508-518 ◽  
Author(s):  
K.John Pasi ◽  
Kathelijn Fischer ◽  
Margaret Ragni ◽  
Beatrice Nolan ◽  
David J. Perry ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Factor Ix ◽  
Safety And Efficacy ◽  
Haemophilia B ◽  
Treatment Groups ◽  
Fc Fusion Protein ◽  
Recombinant Factor Ix ◽  
Bleeding Episodes ◽  
Supplementary Material

SummaryThe safety, efficacy, and prolonged half-life of recombinant factor IX Fc fusion protein (rFIXFc) were demonstrated in the Phase 3 B-LONG (adults/adolescents ≥12 years) and Kids B-LONG (children <12 years) studies of subjects with haemophilia B (≤2 IU/dl). Here, we report interim, long-term safety and efficacy data from B-YOND, the rFIXFc extension study. Eligible subjects who completed B-LONG or Kids B-LONG could enrol in B-YOND. There were four treatment groups: weekly prophylaxis (20–100 IU/kg every 7 days), individualised prophylaxis (100 IU/kg every 8–16 days), modified prophylaxis (further dosing personalisation to optimise prophylaxis), and episodic (ondemand) treatment. Subjects could change treatment groups at any point. Primary endpoint was inhibitor development. One hundred sixteen subjects enrolled in B-YOND. From the start of the parent studies to the B-YOND interim data cut, median duration of rFIXFc treatment was 39.5 months and 21.9 months among adults/adolescents and children, respectively; 68/93 (73.1 %) adults/adolescents and 9/23 (39.1 %) children had ≥100 cumulative rFIXFc exposure days. No inhibitors were observed. Median annualised bleeding rates (ABRs) were low in all prophylaxis regimens: weekly (≥12 years: 2.3; <6 years: 0.0; 6 to <12 years: 2.7), individualised (≥12 years: 2.3; 6 to <12 years: 2.4), and modified (≥12 years: 2.4). One or two infusions were sufficient to control 97 % (adults/adolescents) and 95 % (children) of bleeding episodes. Interim data from B-YOND are consistent with data from B-LONG and Kids B-LONG, and confirm the longterm safety of rFIXFc, absence of inhibitors, and maintenance of low ABRs with prophylactic dosing every 1 to 2 weeks.Supplementary Material to this article is available online at www.thrombosis-online.com.

Depolymerized Holothurian Glycosaminoglycan Inhibits Plasma Thrombin Generation Via Interaction with the Factor IXa Heparin-Binding Exosite

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3081-3081
Author(s):  
Buyue Yang ◽  
John P. Sheehan
Keyword(s):  
Factor Viii ◽  
Thrombin Generation ◽  
Fold Increase ◽  
Factor Ix ◽  
Heparin Binding ◽  
Thrombin Inhibition ◽  
Factor Ixa ◽  
Factor Viiia ◽  
Recombinant Factor Ix ◽  
Inhibition Of Thrombin

Abstract Depolymerized holothurian glycosaminoglycan (DHG) is a fucosylated chrondroitin sulfate that possesses antithrombin-independent antithrombotic properties in rodent thrombosis and dog hemodialysis models. DHG demonstrates significantly less bleeding in template or tail transection assays than therapeutically equivalent doses of heparins. Several potential in vitro mechanisms have been described for DHG, including acceleration of thrombin inhibition by heparin cofactor II (HCII), inhibition of factor VIII activation by thrombin, and inhibition of factor X activation by the intrinsic tenase complex (factor IXa-factor VIIIa). The relevant mechanism(s) for inhibition of tissue factor (TF) induced plasma thrombin generation by DHG were examined in HCII or mock-immunodepleted, and factor-deficient human plasmas, using selected recombinant factor IX(a) with mutations in the heparin-binding exosite. Plasma thrombin generation was detected by fluorogenic substrate cleavage in the presence of corn trypin inhibitor to block contact activation, and compared to a standard curve generated with α2-macroglobulin-thrombin complex. The dose-dependent decrease in velocity index, a parameter reflecting the rate of thrombin generation between lag phase and peak thrombin concentration, was used to compare DHG potency. When triggered by 0.2 pM TF, the EC50 for inhibition of thrombin generation by DHG was 0.16 ± 0.01 μM in both HCII-depleted and mock-depleted plasma, suggesting that DHG acts independently of HCII. When triggered by excess (4 pM) TF, plasma thrombin generation was independent of factors VIII and IX. Under these conditions, the EC50 for DHG inhibition of thrombin generation was increased 13-fold in mock-depleted plasma (2.02 ± 0.09 μM) and 28-fold in HCII-depleted plasma (4.31 ± 0.23 μM). These results suggest that components of the intrinsic tenase complex contribute to inhibition of plasma thrombin generation by DHG, and HCII contributes only at high tissue factor concentrations. In the presence of 0.2 pM TF, Western blotting under nonreducing conditions showed preservation of the prothrombin/meizothrombin band and delayed/reduced thrombin generation in the presence of 0.5 μM DHG, confirming that the inhibition involves reduced prothrombin activation rather than accelerated thrombin inhibition. When triggered by 0.2 pM TF in factor VIII-deficient plasma supplemented with 700 pM factor VIII or thrombin-activated factor VIIIa, the EC50 for inhibition by DHG was 0.41 ± 0.02 μM and 0.44 ± 0.05 μM, respectively. Similarly, the EC50 for DHG inhibition of thrombin generation in factor IX deficient plasma supplemented with 0.2 pM TF and 100% plasma-derived factor IX (90 nM), or 100 pM plasma-derived factor IXa alone, was 0.36 ± 0.01 μM and 0.34 ± 0.02 μM, respectively. Thus, activation of factors VIII and IX do not contribute significantly to the inhibition mechanism for DHG. The contribution of intrinsic tenase activity to DHG inhibition of plasma thrombin generation was assessed using recombinant factor IX(a) mutants with moderate (R170A) or marked (R233A) reductions in heparin affinity. Factor IX deficient plasma was supplemented with 0.2 pM TF and 100% recombinant factor IX, or 100 pM factor IXa, with increasing concentrations of DHG. Similar to plasma-derived factor IX(a), DHG demonstrated an EC50 of 0.38 ± 0.01 μM for inhibition of thrombin generation in the presence of factor IX(a) wild type (WT) zymogen or protease. In the presence of factor IX(a) R170A, the EC50 for DHG was 0.86 ± 0.06 μM and 1.02 ± 0.02 μM, respectively, a 2–3 fold increase relative to WT (P ≤ 0.01). For factor IX(a) R233A, the EC50 for DHG was 3.55 ± 0.47 μM for zymogen and 2.98 ± 0.64 μM for protease, an 8–9 fold increase relative to WT (P ≤ 0.01). Thus, mutations in the factor IXa heparin-binding exosite induced resistance to DHG inhibition of thrombin generation as follows: factor IX(a) R233A&gt; R170A&gt; WT. These findings are consistent with the common mechanism for intrinsic tenase inhibition demonstrated for heparin and DHG in purified systems, and establish the factor IXa heparin-binding exosite as the relevant molecular target for inhibition of plasma thrombin generation by DHG. This antithrombin-independent mechanism likely mediates the antithrombotic efficacy of DHG and related glycosaminoglycans, and may represent a novel therapeutic target with lower bleeding risk.

Long Term Safety and Efficacy of Recombinant Factor IX Fc Fusion Protein (rFIXFc) Prophylaxis in Children with Hemophilia B: Interim Results of the B-Yond Extension Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4976-4976 ◽  
Author(s):  
Jonathan M. Ducore ◽  
Kathelijn Fischer ◽  
Roshni Kulkarni ◽  
Beatrice Nolan ◽  
Carolyn M. Bennett ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Factor Ix ◽  
Hemophilia B ◽  
Advisory Committees ◽  
Safety And Efficacy ◽  
Treatment Groups ◽  
Recombinant Factor Ix ◽  
Bleeding Episodes

Abstract Introduction: The phase 3 Kids B-LONG study (NCT01440946) demonstrated the safety, efficacy, and pharmacokinetics of prophylactic recombinant factor IX Fc fusion protein (rFIXFc) for the prevention and treatment of bleeding episodes in children with severe hemophilia B. The ongoing rFIXFc extension study B-YOND (NCT01425723) is evaluating long-term safety and efficacy of rFIXFc in children and adults with hemophilia B. The safety and efficacy data for pediatric subjects from the second B-YOND interim data cut (11 Sep 2015) are reported here. Methods: The Kids B-LONG study enrolled males aged <12 years with severe hemophilia B (≤2 IU/dL endogenous factor IX [FIX] activity) who had ≥50 exposure days (EDs) of a prior FIX product. Subjects completing Kids B-LONG (median time on study: 49.4 wk) could enroll in 1 of 3 prophylactic treatment groups in B-YOND: weekly prophylaxis (WP; 20-100 IU/kg every 7 d), individualized prophylaxis (IP; 100 IU/kg every 8-16 d), or modified prophylaxis (MP, to optimize prophylaxis with IP or WP). Subjects could change treatment groups at any point in B-YOND. The primary endpoint was development of inhibitors (neutralizing antibody value ≥0.6 BU/mL as measured by the Nijmegen-modified Bethesda assay). Secondary outcomes included annualized bleeding rate (ABR) and rFIXFc exposure days (EDs). Additional outcomes included adverse events (AEs) and evaluation of treatment of bleeding episodes. This analysis reports data for pediatric B-YOND subjects (includes subjects who were <12 y at enrollment into Kids B-LONG) treated with ≥1 dose of rFIXFc. Results: At the time of the second B-YOND interim data cut, 27 subjects had completed Kids B-LONG and enrolled in B-YOND (<6 y cohort, n=13; 6 to <12 y cohort, n=14). Ten subjects had completed (ie, ended participation in the study without premature discontinuation), 16 subjects were ongoing in B-YOND, and 1 subject withdrew due to subject request. From the start of Kids B-LONG to the second B-YOND interim data cut, subjects had a median (range) 2.3 y (0.9-3.0 y) of treatment with rFIXFc, and a median (range) 127.0 (50.0-183.0) cumulative rFIXFc EDs.No inhibitors were observed. AEs were generally typical of the pediatric hemophilia B study population. There were no reports of serious allergic reactions or anaphylaxis associated with rFIXFc, and no vascular thrombotic events; no subjects had AEs related to the study drug. Median (interquartile range [IQR]) overall, spontaneous, and traumatic ABRs were low in both age groups for subjects in the IP and WP treatment groups (Figure; 1 subject in each age cohort was in the MP group [data not shown]). Median (IQR) joint ABRs were 0.0 (0.0-2.2) for subjects < 6 years in the WP treatment group and 0.9 (0.0-2.7) and 1.1 (0.0-2.4) for subjects 6 to <12 years in WP and IP treatment groups, respectively. Regardless of age or treatment group, the majority of bleeding episodes were controlled with 1-2 intravenous injections (<6 y, 97.3%; 6 to <12 y, 97.2%). At the end of Kids B-LONG, 26/27 subjects were dosing once weekly and 1/27 subject was dosing every 5 days. Compared with these dosing intervals, 14.8% of subjects lengthened, 77.8% of subjects did not change, and 7.4% of subjects decreased their prophylactic dosing interval during B-YOND. The median (IQR) dosing interval during B-YOND for pediatric subjects in the IP treatment groups was 10.0 [10.0, 10.7] days. Compared with the end of B-LONG, the median (IQR) total weekly prophylactic dose of rFIXFc was similar at the second B-YOND interim data cut (60.0 [50.0-60.0] vs 60.0 [57.0-70.0]). Conclusion: These data confirm the long-term safety of rFIXFc with maintenance of low ABRs and extended-interval prophylaxis in children with hemophilia B. This research was funded by Biogen and Sobi. Biogen and Sobi reviewed and provided feedback on the abstract. The authors had full editorial control of the abstract and provided their final approval of all content. Disclosures Ducore: Octapharama: Membership on an entity's Board of Directors or advisory committees; Baxalta (Shire): Membership on an entity's Board of Directors or advisory committees; LFB: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Biogen: Membership on an entity's Board of Directors or advisory committees. Fischer:Baxter: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Speakers Bureau; Biogen: Consultancy; Biotest: Consultancy, Speakers Bureau; Baxalta/Baxter: Consultancy, Research Funding, Speakers Bureau; Wyeth: Research Funding; Pfizer: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Freeline: Consultancy. Kulkarni:Kedrion: Membership on an entity's Board of Directors or advisory committees; BPL: Membership on an entity's Board of Directors or advisory committees; Biogen: Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nolan:Sobi: Research Funding; Biogen: Research Funding. Perry:Biogen: Consultancy, Honoraria; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees. Yuan:Biogen: Employment, Equity Ownership. Ramirez-Santiago:Biogen: Employment, Equity Ownership. Ferrante:Sobi: Employment. Lethagen:Sobi: Employment.

The Effect of Factor IXa on Thrombin Generation Activity Determination: rFIXFc Vs. BeneFIX®

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2266-2266
Author(s):  
Yang Buyue ◽  
Ekta Seth Chhabra ◽  
Li Wang ◽  
Jurg M Sommer
Keyword(s):  
Tissue Factor ◽  
Thrombin Generation ◽  
Time Course ◽  
Drug Product ◽  
Factor Ix ◽  
One Stage ◽  
Thrombin Generation Assay ◽  
Factor Ixa ◽  
Recombinant Factor Ix

Abstract Abstract 2266 Recombinant Factor IX Fc fusion (rFIXFc) was designed to be a long-lasting version of recombinant FIX that has the potential to provide less frequent dosing. This may be applicable to prophylaxis and on-demand therapy of hemophilia B and for control of bleeding during surgery. The potency of the rFIXFc drug product, as well as the commercially available recombinant factor IX, BeneFIX®, is assigned by a one-stage clotting assay. The thrombin generation assay (TGA), a global hemostasis assay that monitors the amount of active thrombin produced in patient plasma after recalcification, represents a useful indication in the evaluation of coagulation capacity of hemophilic plasma. When equal units of rFIXFc and BeneFIX, as determined by the one stage assay, were spiked into hemophilic plasma and their coagulation capacity was assessed by the TGA, BeneFIX generated 2-fold higher peak thrombin and significantly left-shifted thrombin curve relative to rFIXFc in the presence of limiting tissue factor and 4 μM phospholipids. In an assay control without tissue factor triggering, BeneFIX demonstrated considerable thrombogenic activity, whereas rFIXFc was essentially inactive. Since BeneFIX was observed to have a markedly higher level of FIXa impurity than rFIXFc in a factor IXa ELISA, and since factor IXa protease is known to be highly thrombogenic in an in vivo model, we hypothesized that the enhanced in vitro thrombin generation profile of BeneFIX may be due to the presence of excess factor IXa. BeneFIX was incubated overnight with a serine protease active site blocker, EGR-chloromethyl ketone, and dialyzed by extensive buffer exchange. The FIXa-blocked BeneFIX showed very similar thrombin generation profile (ETP, peak thrombin, time course and slope) to rFIXFc, confirming the role of FIXa in thrombin generation by BeneFIX. To quantify the amount of active factor IXa in BeneFIX and rFIXFc, a plasma-derived factor IXa (pFIXa) standard curve was constructed by spiking increasing concentrations of factor IXa (0–100 pM) into human factor IX-deficient plasma in the presence of 4 μM phospholipids. Prior to starting the measurement, 5 nM thrombin was added to the assay in order to improve sensitivity. A dose response was observed with a detection limit as low as 0.5 pM pFIXa in FIX-deficient plasma. BeneFIX, FIXa-blocked BeneFIX and rFIXFc of equal potency (1 IU/mL by the one-stage clotting assay) generated thrombin responses comparable to 20 pM, 1 pM and 2 pM pFIXa, respectively, indicating the amount of FIXa present in each FIX product. In a regular thrombin generation assay triggered with limiting tissue factor, 1 IU/mL rFIXFc supplemented with 20 pM pFIXa demonstrated an equal peak thrombin and velocity index to 1 IU/mL BeneFIX. These data suggest that: 1) Minor amounts of FIXa protease in a FIX drug product (0.1%) can trigger significant thrombin generation in global hemostasis assays 2) Thrombin generation assay could be used to evaluate FIXa level in FIX products with high sensitivity (0.5 pM FIXa per IU/ml FIX) 3) the higher peak thrombin and shortened time course in the thrombin generation profile for BeneFIX relative to rFIXFc is caused entirely by the presence of factor IXa in the drug product 4) Discounting the rFIXa impurities in these drug products, BeneFIX and rFIXFc have equivalent in vitro thrombin generation activity per unit of FIX activity. Disclosures: Buyue: Biogen Idec Hemophilia: Employment. Seth Chhabra:Biogen Idec Hemophilia: Employment. Wang:Biogen Idec Hemophilia: Employment. Sommer:Biogen Idec Hemophilia: Employment.

Analysis of Target Joint Bleeding with Prophylactic Use of Recombinant Factor IX Fc Fusion Protein in Patients with Severe Hemophilia B

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2294-2294
Author(s):  
Amy D Shapiro ◽  
David J Perry ◽  
Ross I Baker ◽  
Elisa Tsao ◽  
Baisong Mei
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Factor Ix ◽  
Hemophilia B ◽  
Severe Hemophilia ◽  
Bleeding Events ◽  
Advisory Committees ◽  
Recombinant Factor Ix ◽  
Bleeding Episodes ◽  
Dosing Intervals

Abstract Background: The phase 3 B-LONG study demonstrated the safety, efficacy, and pharmacokinetics of recombinant factor IX Fc fusion protein (rFIXFc) for the prevention and treatment of bleeding episodes in subjects with severe hemophilia B. For people with hemophilia, frequent bleeding events occur in target joints, which are a known precursor to hemophilic arthropathy (chronic joint disease). There is currently limited information available on the outcomes of prophylaxis in subjects with target joints who have severe hemophilia B. Aims: To assess the frequency of bleeding events and the dosing of rFIXFc in subjects who had ≥1 target joint at baseline in the B-LONG study. Methods: B-LONG was a Phase 3, multicenter, open-label study that enrolled males aged ≥12 years with severe hemophilia B (≤2 IU/dL endogenous FIX activity) who had received prior treatment with FIX. Subjects in B-LONG were enrolled into 1 of 4 arms: Arm 1, weekly prophylaxis; Arm 2, individualized interval prophylaxis; Arm 3, episodic treatment; or Arm 4, perioperative management. For the current post-hoc analysis, subjects with ≥1 target joint at baseline (per protocol, a target joint was defined as a major joint with ≥3 bleeding episodes in a 3-month period) and who received on-study rFIXFc prophylaxis (Arms 1 and 2 only) were included. On-study per subject target joint ABR (annualized number of bleeding episodes per year in all target joints combined), including overall, spontaneous, and traumatic target joint ABR, were assessed. In subjects with available prestudy and on-study ABR data, prestudy 12-month bleeding rates were compared with on-study overall ABR. Results: Forty-three subjects from the prophylaxis arms had target joints at entry into B-LONG and data collected during the efficacy period of the study (weekly prophylaxis, n = 35; individualized interval prophylaxis, n = 8). Of these, 40 subjects had both prestudy and on-study bleeding information available. Regardless of prestudy treatment regimen (prophylactic or episodic rFIX), on-study median ABRs were low among subjects with target joints at baseline compared with prestudy ABRs (Fig. 1). The on-study overall target joint, spontaneous target joint, and traumatic target joint median (interquartile range, [IQR]) ABRs were low for subjects in the weekly prophylaxis arm (1.03 [0.00, 3.07], 0.00 [0.00, 1.10], and 0.00 [0.00, 1.11], respectively) and for subjects in the individualized interval prophylaxis arm (2.20 [0.00, 3.75], 2.20 [0.00, 3.75], and 0.00 [0.00, 0.00], respectively; Fig. 2). A total of 17 (48.6%) subjects receiving weekly prophylaxis and 3 (37.5%) subjects receiving individualized interval prophylaxis had no target joint bleeding episodes on-study. The average weekly prophylactic rFIXFc dose for subjects with target joints at baseline was (median [IQR]) 46.26 (37.98, 54.55) IU/kg and 69.48 (57.28, 77.45) IU/kg for those receiving weekly prophylaxis and individualized interval prophylaxis, respectively. The median (IQR) average on-study dosing intervals for these groups were 6.98 (6.88, 7.00) days and 10.25 (9.45, 12.72) days, respectively. Among subjects with target joints at baseline who received prestudy rFIX and on-study rFIXFc prophylaxis (n = 6, weekly prophylaxis arm only; no subjects from the individualized interval prophylaxis arm who met these criteria had available data), the on-study median (IQR) average weekly prophylactic dose of 50.61 (39.61, 60.61) IU/kg with rFIXFc was lower than the prestudy median (IQR) average weekly prophylactic dose of 111.28 (95.56, 116.76) IU/kg with rFIX. Additionally, the on-study median (IQR) dosing interval (6.92 [6.79, 6.97]) with rFIXFc prophylaxis was longer than the pre-study median (IQR) dosing interval among these 6 subjects (3.50 [2.33, 3.50] days). Summary/Conclusion: For subjects in the current analysis with severe hemophilia B who entered B-LONG with target joints, rFIXFc prophylaxis was effective for reducing the frequency of bleeding episodes overall and in target joints. Furthermore, in subjects who received prestudy and on-study prophylaxis, rFIXFc was associated with reduced consumption and prolonged dosing intervals compared with conventional prestudy rFIX products. These results suggest that target joints can be effectively managed and controlled with rFIXFc dosed prophylactically every 1 to 2 weeks. Disclosures Shapiro: Baxalta, Novo Nordisk, Biogen, ProMetic Life Sciences, and Kedrion Biopharma: Consultancy; Biogen: Speakers Bureau; Bayer Healthcare, Baxalta, Biogen, CSL Behring, Daiichi Sankyo, Kedrion Biopharma, Octapharma, OPKO, ProMetic Life Sciences, PTC Therapeutics, and Selexys: Research Funding; Baxalta, Novo Nordisk, Biogen,: Membership on an entity's Board of Directors or advisory committees. Perry:Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Biogen: Consultancy, Honoraria. Baker:Biogen Idec: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingelheim: conference travel support, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter Healthcare: Membership on an entity's Board of Directors or advisory committees, Other: conference travel support, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Research Funding; Portola Pharmaceuticals: Research Funding; Astellas: Research Funding; CSL Behring: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: conference travel support; Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Other: conference travel support; Bristol- Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Other: conference travel support. Tsao:Biogen: Employment, Equity Ownership. Mei:Biogen: Employment, Equity Ownership.

Recombinant Factor IX

1997 ◽  
Vol 78 (01) ◽  
pp. 261-265 ◽  
Author(s):  
Gilbert C White ◽  
Aime Beebe ◽  
Brenda Nielsen
Keyword(s):  
Factor Ix ◽  
Recombinant Factor Ix

In Vitro Thrombogenicity Tests of Factor IX Concentrates

1979 ◽  
Vol 42 (05) ◽  
pp. 1355-1367 ◽  
Author(s):  
C V Prowse ◽  
A Chirnside ◽  
R A Elton
Keyword(s):  
Factor Viii ◽  
Partial Thromboplastin Time ◽  
Generation Time ◽  
Activated Partial Thromboplastin Time ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Factor Viii Inhibitor ◽  
Factor Ixa ◽  
Viii Inhibitor

SummaryVarious factor IX concentrates have been examined in a number of in vitro tests of thrombogenicity. The results suggest that some tests are superfluous as in concentrates with activity in any of these tests activation is revealed by a combination of the non-activated partial thromboplastin time, the thrombin (or Xa) generation time and factor VIII inhibitor bypassing activity tests. Assay of individual coagulant enzymes revealed that most concentrates contained more factor IXa than Xa. However only a small number of concentrates, chiefly those that had been purposefully activated, contained appreciable amounts of either enzyme.

Sign in / Sign up

Export Citation Format

Share Document