A prospective surveillance study in haemophilia B patients following a population switch to recombinant factor IX (nonacog gamma)

Haemophilia ◽  
2021 ◽  
Author(s):  
Evemie Dubé ◽  
Clémence Merlen ◽  
Arnaud Bonnefoy ◽  
Julie Gauthier ◽  
Jean‐François Castilloux ◽  
...  
Keyword(s):  
Factor Ix ◽  
Surveillance Study ◽  
Prospective Surveillance ◽  
Haemophilia B ◽  
Recombinant Factor Ix

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.

scholarly journals Real‐world data demonstrate improved bleed control and extended dosing intervals for patients with haemophilia B after switching to recombinant factor IX Fc fusion protein (rFIXFc) for up to 5 years

Haemophilia ◽  
2020 ◽  
Vol 26 (6) ◽  
pp. 975-983
Author(s):  
Amy Shapiro ◽  
Ateefa Chaudhury ◽  
Michael Wang ◽  
Miguel Escobar ◽  
Elisa Tsao ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Real World ◽  
Factor Ix ◽  
Real World Data ◽  
World Data ◽  
Haemophilia B ◽  
Fc Fusion Protein ◽  
Recombinant Factor Ix ◽  
Dosing Intervals

Idelvion® as a modern treatment option for haemophilia B (Sponsor: CSL Behring GmbH)

2020 ◽  
Vol 12 (01) ◽  
pp. 1-20
Keyword(s):  
Fusion Protein ◽  
Safety Profile ◽  
Factor Ix ◽  
Efficacy And Safety ◽  
Haemophilia B ◽  
Previous Therapy ◽  
Injection Frequency ◽  
Recombinant Factor Ix ◽  
Modern Treatment ◽  
Long Acting

ZusammenfassungIdelvion® (albutrepenonacog alfa, rIX-FP) is a long-acting recombinant factor IX (FIX) albumin fusion protein indicated for the treatment and prophylaxis of bleeding in patients with haemophilia B. It allows prophylaxis intervals of up to 14 days.* Compared with previous therapy, this fusion protein allows for a significant reduction in injection frequency while maintaining a favourable efficacy and safety profile.

FIX-Triple, a gain-of-function factor IX variant, improves haemostasis in mouse models without increased risk of thrombosis

2010 ◽  
Vol 104 (08) ◽  
pp. 355-365 ◽  
Author(s):  
Chung-Yang Kao ◽  
Chia-Ni Lin ◽  
I-Shing Yu ◽  
Mi-Hua Tao ◽  
Hua-Lin Wu ◽  
...  
Keyword(s):  
Mouse Models ◽  
Specific Activity ◽  
Factor Ix ◽  
Wild Type ◽  
Haemophilia B ◽  
Virus Particles ◽  
Thrombosis Risk ◽  
Increased Risk ◽  
Recombinant Factor Ix ◽  
Fold Excess

SummaryEngineered recombinant factor IX (FIX) with augmented clotting activity may prove useful for replacement therapy, but it has not been studied for risk of thrombosis. We used three mouse models to evaluate thrombosis risk associated with the FIX variant FIX-Triple, which has a 13-fold higher specific activity than wild-type FIX (FIX-WT). Protein infusion of FIX-Triple into haemophilia B mice was not thrombogenic, even at a dose of 13-fold higher than FIX-WT. Gene knock-in to generate mice that constitutively produce FIX-WT or FIX-Triple protein revealed that all mice expressed equal antigen levels. FIX-Triple knock-in mice that exhibited 10-fold higher FIX clotting activity did not show hypercoagulation. Adeno-associated viral (AAV) delivery of the FIX gene into mice was used to mimic gene therapy. Haemophilia B and inbred C57Bl/6 mice injected with different doses of virus particles carrying FIX-WT or FIX-Triple and expressing up to a nearly 13-fold excess (1289% of normal) of FIX clotting activity did not show increased risk of thrombosis compared with untreated wild-type mice in a normal haemostatic state. When challenged with ferric chloride (FeCl3), the mesenteric venules of AAV-treated C57Bl/6 mice that gave a nearly five-fold excess (474%) of FIX clotting activity were not thrombotic; however, thrombosis became obvious in FeCl3-challenged mice expressing extremely high FIX clotting activities (976–1289%) achieved by AAV delivery of FIX-Triple. These studies suggest that FIX-Triple is not thrombogenic at therapeutic levels and is a potential therapeutic substitute for FIX-WT.

Treatment of intracranial and extracranial haemorrhages in a neonate with severe haemophilia B with recombinant factor IX infusion

Haemophilia ◽  
2005 ◽  
Vol 11 (4) ◽  
pp. 411-414 ◽  
Author(s):  
G. M. T. Guilcher ◽  
M.-F. Scully ◽  
M. Harvey ◽  
J. P. Hand
Keyword(s):  
Factor Ix ◽  
Severe Haemophilia ◽  
Haemophilia B ◽  
Recombinant Factor Ix

Recombinant factor IX Fc fusion protein in children with haemophilia B (Kids B-LONG): results from a multicentre, non-randomised phase 3 study

2017 ◽  
Vol 4 (2) ◽  
pp. e75-e82 ◽  
Author(s):  
Kathelijn Fischer ◽  
Roshni Kulkarni ◽  
Beatrice Nolan ◽  
Johnny Mahlangu ◽  
Savita Rangarajan ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Factor Ix ◽  
Phase 3 ◽  
Haemophilia B ◽  
Fc Fusion Protein ◽  
Recombinant Factor Ix

Evaluation of the Safety, Efficacy of Recombinant Factor IX (nonacog alfa) in Japanese Patients with Hemophilia B- Interim Result of Post Marketing Surveillance Study -

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3378-3378
Author(s):  
Takashi Suzuki ◽  
Katsuyuki Fukutake ◽  
Kagehiro Amano ◽  
Hideji Hanabusa ◽  
Masashi Taki ◽  
...  
Keyword(s):  
Research Funding ◽  
Factor Ix ◽  
Hemophilia B ◽  
Surveillance Study ◽  
Interim Result ◽  
Average Dose ◽  
Registration System ◽  
On Demand ◽  
Post Marketing Surveillance ◽  
Recombinant Factor Ix

Abstract Abstract 3378 Objective: Nonacog alfa (Benefix®) has been available in Japan since January 2010 and is being used widely for prophylaxis in patients with hemophilia B as the first recombinant factor IX. We have been conducting a surveillance study in order to investigate adverse events, safety and efficacy with routine use conditions in all patients receiving Benefix. The recovery of recombinant factor IX was measured to assess factors affecting appropriate dosing of nonacog alfa. Method: All patients who were administered Benefix were enrolled in this study by central registration system until 300 patients were registered. The initial dose was around 50 IU/kg, but subsequent doses may have been modified according to condition of the patient and recovery. Observation period was 12 and 24 months for previously treated patient (PTP) and previously untreated patients (PUP), respectively. Follow up data (e.g. bleeding episode, adverse event, status of administration, etc) was recorded for every 6 month period. Result: 319 patients including 32 PUPs were registered from 173 institutions during 2 years. 177 patients including 14 PUPs were included in this interim analysis as the data cutoff was Jan 2012. Duration of the observation was 6 to 12 months (PUPs: 6 to 18 months). Disease severity was 52.0% (severe), 28.8% (moderate), 15.8% (mild) and 3.4% (unknown). Total frequency of the administration was 1 to 240 infusions (median: 41 infusions). Some patients received more than one Benefix regimen (e.g. prophylaxis + on demand) and assessment was conducted by each regimen (prophylaxis: 98, on demand: 55, hemostasis during surgery: 13, others: 38). Total 512 bleeding episodes (spontaneous: 440, traumatic: 66, unknown: 6) were reported from 55 patients who received on demand therapy. An average of 2.2 times infusions was needed for hemostasis. The average dose was 41IU/kg. Regarding 98 patients who received prophylactic regimen, the most common regimen was twice-weekly administration (62.4%) and its average dose was 40 IU/kg. Analyzed by age, the average dose was 44 IU/kg and 35 IU/kg for <15 years old and ≥ 15 years old, respectively. No bleeding was observed in 68.3% (by age: 75.0% of <15 years old, 62.8% of ≥ 15 years old). Average frequency of bleeding was 3.8 times (median: 2, max: 45) in 6 months period. Factor IX levels were measured in 82 patients after first dose (median dose: 44IU/kg, range: 17 to 120 IU/kg). Median reciprocal of observed recovery was 1.28 (min-max). Weak negative correlation (r2 = 0.463, p=0.036) was observed between weight and recovery. A correlation was not seen between the recovery and age. Adverse drug reaction was observed 2.3% of patients (2 headaches, 1 vertigo, 1 dyspnea, 1 nausea, 1 urticaria and 1 itching of injection site). No patients developed inhibitor related to nonacog alfa. Conclusion: Nonacog alfa was safe and effective on both prophylactic and on demand regimen in clinical practice. 68.3 % of no bleeding rate was comparable to plasma-derived factor IX. The variability in recovery was consistent with what has been reported by others. This surveillance study is still ongoing and final result will be obtained in year 2014. Disclosures: Suzuki: Pfizer Japan Inc.: Research Funding. Fukutake:Pfizer Japan Inc.: Research Funding. Amano:Pfizer Japan Inc.: Research Funding. Hanabusa:Pfizer Japan Inc.: Research Funding. Taki:Pfizer Japan Inc.: Research Funding. Matsushita:Pfizer Japan Inc.: Research Funding. Shima:Pfizer Japan Inc.: Research Funding. Sakai:Pfizer Japan Inc.: Research Funding. Iizuka:Pfizer Japan Inc: Employment. Shibasaki:Pfizer Japan Inc.: Employment.

scholarly journals Pharmacokinetics, safety and efficacy of a recombinant factor IX product, trenonacog alfa in previously treated haemophilia B patients

Haemophilia ◽  
2017 ◽  
Vol 24 (1) ◽  
pp. 104-112 ◽  
Author(s):  
P. W. Collins ◽  
D. V. K. Quon ◽  
M. Makris ◽  
P. Chowdary ◽  
C. L. Kempton ◽  
...  
Keyword(s):  
Factor Ix ◽  
Safety And Efficacy ◽  
Haemophilia B ◽  
Recombinant Factor Ix ◽  
Previously Treated

Use of recombinant factor IX in subjects with haemophilia B undergoing surgery

Haemophilia ◽  
2002 ◽  
Vol 8 (2) ◽  
pp. 91-97 ◽  
Author(s):  
M. V. RAGNI ◽  
K. J. PASI ◽  
G. C. WHITE ◽  
P. L. GIANGRANDE ◽  
S. G. COURTER ◽  
...  
Keyword(s):  
Factor Ix ◽  
Haemophilia B ◽  
Recombinant Factor Ix

scholarly journals Postmarketing safety and effectiveness of recombinant factor IX (nonacog alfa) in Japanese patients with haemophilia B

Haemophilia ◽  
2019 ◽  
Vol 25 (4) ◽  
Author(s):  
Katsuyuki Fukutake ◽  
Masashi Taki ◽  
Tadashi Matsushita ◽  
Michio Sakai ◽  
Ami Takata ◽  
...  
Keyword(s):  
Japanese Patients ◽  
Factor Ix ◽  
Haemophilia B ◽  
Recombinant Factor Ix
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