scholarly journals Perioperative haemostasis with full‐length, PEGylated, recombinant factor VIII with extended half‐life (rurioctocog alfa pegol) in patients with haemophilia A: Final results of a multicentre, single‐arm phase III trial

Haemophilia ◽  
2019 ◽  
Vol 25 (5) ◽  
pp. 773-781 ◽  
Author(s):  
Ralph Gruppo ◽  
Maria‐Fernanda López‐Fernández ◽  
Tung T. Wynn ◽  
Werner Engl ◽  
Marlies Sharkhawy ◽  
...  
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Phase Iii ◽  
Haemophilia A ◽  
Phase Iii Trial

Safety and efficacy of sucrose-formulated full-length recombinant factor VIII: Experience in the standard clinical setting

2008 ◽  
Vol 99 (01) ◽  
pp. 52-58 ◽  
Author(s):  
Elena Santagostino ◽  
Albert Faradji ◽  
Alfonso Iorio ◽  
Jan van der Meer ◽  
Jørgen Ingerslev ◽  
...  
Keyword(s):  
Observational Study ◽  
Factor Viii ◽  
De Novo ◽  
Observation Time ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Phase Iii ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Safety And Efficacy

SummaryThe safety of full-length sucrose-formulated recombinant factor VIII (rFVIII-FS; KOGENATE® FS) for up to 24 months of use was evaluated in a postmarketing observational study in Europe. Long-term safety and efficacy data were available for 212 patients with severe haemophilia A, including 13 previously untreated patients (PUPs) and 12 patients with 1–19 exposure days (EDs). Patients accumulated a mean (± SD) of 187 (121) EDs to rFVIII-FS and received a total of 39,627 infusions, mainly for prophylaxis and for the treatment of 4,283 spontaneous or trauma-related bleeds during an average observation time of 710 (136) days. Of these bleeding episodes, 85.4% were successfully treated with one or two infusions of rFVIII-FS. Haemostasis was also evaluated during 46 minor to major surgical pro- cedures, and the response to infusion was “excellent” or “good” in all cases. FVIII inhibitor formation was observed in six patients (two de novo; four persistent or recurrent). The de novo cases represent 8.0% (2 of 25) of patients who reported 0–19 previous EDs at study entry. Four of the five patients who reported possible drug-related adverse effects developed inhibitors. The results of this observational study demonstrate the efficacy and safety of rFVIII-FS during normal clinical use in the treatment of patients with severe haemophilia A. Furthermore, these findings are consistent with those of previous phase III clinical studies with rFVIII-FS, particularly with regard to its efficacy and low incidence of inhibitor formation.

scholarly journals Once‐weekly prophylaxis with glycoPEGylated recombinant factor VIII (N8‐GP) in severe haemophilia A: Safety and efficacy results from pathfinder 2 (randomized phase III trial)

Haemophilia ◽  
2019 ◽  
Vol 25 (3) ◽  
pp. 373-381 ◽  
Author(s):  
Nicola Curry ◽  
Canan Albayrak ◽  
Miguel Escobar ◽  
Pål Andre Holme ◽  
Susan Kearney ◽  
...  
Keyword(s):  
Factor Viii ◽  
Recombinant Factor Viii ◽  
Phase Iii ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Phase Iii Trial ◽  
Safety And Efficacy

scholarly journals Efficacy and safety of pegylated full‐length recombinant factor VIII with extended half‐life for perioperative haemostasis in haemophilia A patients

Haemophilia ◽  
2016 ◽  
Vol 22 (4) ◽  
Author(s):  
B. Brand ◽  
R. Gruppo ◽  
T. T. Wynn ◽  
L. Griskevicius ◽  
M. F. Lopez Fernandez ◽  
...  
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Haemophilia A ◽  
Efficacy And Safety

scholarly journals Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A

Haemophilia ◽  
2016 ◽  
Vol 23 (2) ◽  
pp. 238-246 ◽  
Author(s):  
E. S. Mullins ◽  
O. Stasyshyn ◽  
M. T. Alvarez-Román ◽  
D. Osman ◽  
R. Liesner ◽  
...  
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Haemophilia A ◽  
Severe Haemophilia

An observational study of sucrose-formulated recombinant factor VIII for Japanese patients with haemophilia A

2008 ◽  
Vol 100 (07) ◽  
pp. 32-37 ◽  
Author(s):  
Chiho Ikegawa ◽  
ChisatoYo koyama ◽  
Verena Haupt ◽  
Jean-Christophe Delumeau
Keyword(s):  
Observational Study ◽  
Factor Viii ◽  
De Novo ◽  
Severe Disease ◽  
Japanese Patients ◽  
Recombinant Factor Viii ◽  
Phase Iii ◽  
Haemophilia A ◽  
Postmarketing Surveillance Study ◽  
Usual Clinical Practice

SummaryThe safety and efficacy of sucrose-formulated recombinant factor VIII (rFVIII-FS; Kogenate® FS) under usual clinical practice were evaluated for 12 months in an observational, postmarketing surveillance study conducted at 214 treatment centres throughout Japan. The study included 631 patients with haemophilia A, 80% of whom had severe or moderately-severe disease (≤2% FVIII:C).Most patients (n=477;75.6%) had >100 prior exposure days (EDs), but the study also included 62 (9.8%) patients with <20 EDs who were at high risk for inhibitor development. A total of 71,240 infusions were administered during the observation (mean, 113 ± 108 per patient). Physicians rated efficacy and tolerability of rFVIII-FS as “very good” or “good” in >99% of patients. FVIII inhibitors were observed in seven patients (5 de novo; 1 persistent/fluctuating; 1 recurrent).The overall de novo inhibitor incidence was 0.8% (5/631; or 5/599 among the subgroup of patients with negative baseline titre and no known inhibitor history).De novo cases represented 3.2% (2/62) of patients with <20 EDs at enrollment (2/57 in the no inhibitor subgroup) and 0.2 % (1/477) of patients pretreated with >100 EDs (1/452 in the no inhibitor subgroup) at enrollment. The results of this large observational study demonstrate that rFVIII-FS is both safe and efficacious as used in the usual clinical setting for the treatment of Japanese patients with mild to severe haemophiliaA. This study supports the efficacy of rFVIII-FS with an incidence of inhibitor formation no greater than in a comparable European study or previous phase III clinical studies.

Perioperative Efficacy of an Extended Half-Life, Pegylated, Full-Length, Recombinant Factor VIII (BAX 855) in Individual Procedures

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2299-2299
Author(s):  
Brigitte Brand ◽  
Ralph A. Gruppo ◽  
Tung T. Wynn ◽  
Laimonas Griskevicius ◽  
Maria Fernanda Lopez Fernandez ◽  
...  
Keyword(s):  
Blood Loss ◽  
Factor Viii ◽  
Half Life ◽  
Research Funding ◽  
Hemophilia A ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Employment Equity ◽  
Major Procedure ◽  
Equity Ownership

Abstract BAX 855 is a pegylated full-length recombinant factor VIII (PEG rFVIII) built on rFVIII (ADVATE) with an extended half-life and is intended for prophylaxis and the treatment of bleeding in patients with hemophilia A.1 This phase 3 surgery study is evaluating the efficacy and safety of BAX 855 for the perioperative control of hemostasis. Patients' informed consent and appropriate ethics committee approvals were obtained. Elective procedures were prospectively classified (major or minor) by the investigator/surgeon and major emergency surgeries were excluded. The target trough FVIII levels for major and minor surgeries were to be ≥80% and 30-60%, respectively. Each patient's pharmacokinetic (PK) profile was used to guide the BAX 855 dose and infusion frequency. BAX 855 PK were consistent with previous PK assessments with terminal half-life ranging from 8.81 to 18.06 hours for the 15 patients in this study. In this interim analysis, 15 male previously treated patients (PTPs) ranging from 19 to 52 years of age have undergone 15 procedures in 7 countries. Individual procedure profiles are compiled to evaluate the control of hemostasis for BAX 855. There were 11 major procedures: 6 orthopedic (3 knee replacements, 2 arthroscopic synovectomies, 1 elbow cyst extirpation) and 5 non-orthopedic procedures (3 dental [root canals for 2 teeth, 2 extractions of ≥4 teeth, 1 radicular cyst removal], 1 cardiovascular [mediport placement], 1 abdominal [gastric band insertion]). The 4 minor surgeries comprised 1 synoviorthesis, 1 dental, 1 dermatological and 1 endoscopy (radiosynovectomy) procedure. Efficacy was evaluated by the surgeon or investigator's rating of hemostatic control using 4-point scale which was based on blood loss and by comparing actual blood loss with predicted blood loss which was specified by the surgeon for non-hemophilia patients prior to the procedure. For all procedures, the hemostatic control of BAX 855 was rated "excellent" for the intraoperative (during the procedure), postoperative (24 hours after completion of the procedure), and perioperative (from start of the procedure until discharge or day 14) periods, except for 1 minor dental procedure in which postoperative efficacy was rated "good" and 1 minor procedure in which a postoperative rating was not provided (for both of these procedures intra- and perioperative ratings were "excellent"). Actual blood loss (ABL) for the intraoperative and postoperative periods were compared with predicted average and maximum values. Intraoperative ABL for all minor and major procedures was less than or equal to predicted averages and maximums, except for 1 minor procedure in which the ABL was greater than the predicted average and maximum and 1 major procedure which did not have ABL recorded. Postoperative ABL was less than or equal to predicted averages and maximums for 4/4 minor procedures and 5 major procedures. For 4 major procedures, postoperative ABL was greater than or equal to predicted average, but less than predicted maximums. For the remaining major procedure (synovectomy with general anesthesia) with reported ABL, postoperative ABL was greater than the predicted the average and maximum - the efficacy assessments at all periods for this procedure were considered "excellent". These results demonstrate the efficacy of BAX 855 for the perioperative control of hemostasis in patients with severe hemophilia A. 1 Konkle BA, Stasyshyn O, Chowdary P et al. Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A. Blood. 2015; Link to Publisher's site: http://www.bloodjournal.org/content/bloodjournal/early/2015/07/08/blood-2015-03-630897.full.pdf Disclosures Brand: CSL Behring: Consultancy; Pfizer: Consultancy; Bayer: Consultancy; Baxalta: Consultancy, Research Funding; Novo Nordisk: Consultancy; Biotest: Consultancy. Gruppo:Baxalta: Consultancy, Research Funding; Novo Nordisk: Consultancy; Pfizer: Consultancy; Alexion: Speakers Bureau. Wynn:Baxalta: Research Funding. Griskevicius:Novartis: Consultancy, Research Funding; Baxalta: Research Funding. Fernanda Lopez Fernandez:Baxalta: Research Funding. Dvorak:Baxalta: Employment, Equity Ownership. Patrone:Baxalta: Employment, Equity Ownership. Abbuehl:Baxalta: Employment, Equity Ownership.

Low risk of inhibitor formation in haemophilia A patients following en masse switch in treatment to a third generation full length plasma and albumin-free recombinant factor VIII product (ADVATE®)

Haemophilia ◽  
2011 ◽  
Vol 17 (3) ◽  
pp. 407-411 ◽  
Author(s):  
C. L. BACON ◽  
E. SINGLETON ◽  
B. BRADY ◽  
B. WHITE ◽  
B. NOLAN ◽  
...  
Keyword(s):  
Factor Viii ◽  
Low Risk ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Haemophilia A ◽  
Third Generation ◽  
Viii Product

Full-length sucrose-formulated recombinant factor VIII for treatment of previously untreated or minimally treated young children with severe haemophilia A

2005 ◽  
Vol 93 (03) ◽  
pp. 457-467 ◽  
Author(s):  
Joan Gill ◽  
Chantal Rothschild ◽  
Marilyn Manco-Johnson ◽  
Jeanne Lusher ◽  
Elke Kellermann ◽  
...  
Keyword(s):  
Young Children ◽  
Factor Viii ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Bleeding Complications ◽  
Adverse Event Rate ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Safety And Efficacy ◽  
Mean Values

SummaryThe safety and efficacy of a full-length sucrose-formulated recombinant factor VIII product (rFVIII-FS; KogenateFS; Kogenate Bayer) was evaluated in previously untreated (PUPs) and minimally treated (MTP) patients with severe haemophilia A (FVIII < 2%). Patients (37 PUPs; 24 MTPs) aged 0.1–25.7 months were treated with rFVIII-FS for a cumulative of 9,141 exposure days (EDs), median 114 EDs (range 4–478), on prophylactic or on-demand therapy. Eighty-nine percent of all treated bleeding episodes were successfully treated with 1 (74%) or 2 (15%) infusions. Clinical response to first infusion for each bleeding episode was rated as ‘excellent’ in 58%, or ‘good’ in 33%, of all cases. Recombinant FVIII-FS was used in 27 surgical procedures, mainly catheter implantations, which were all conducted without bleeding complications. FVIII recovery mean values (~2%/kg/ IU) were as expected for any licensed FVIII concentrate. FVIII neutralizing antibody formation was 15% (9/60). Aside from inhibitor formation, three adverse events were rated as ‘at least possibly drug-related’ for a total drug-related adverse event rate of 0.14%. No viral seroconversions were observed. Overall, excellent safety and efficacy were demonstrated with rFVIII-FS for therapy of young children with severe haemophilia A.

Low risk of inhibitor formation in haemophilia patients after a change in treatment from Chinese hamster ovary cell-produced to baby hamster kidney cell-produced recombinant factor VIII

2007 ◽  
Vol 98 (12) ◽  
pp. 1188-1192 ◽  
Author(s):  
Jude Smith ◽  
Mary Kavanagh ◽  
Beatrice Nolan ◽  
Barry White ◽  
Evelyn Singleton
Keyword(s):  
Factor Viii ◽  
Chinese Hamster Ovary ◽  
De Novo ◽  
Chinese Hamster ◽  
Low Risk ◽  
Recombinant Factor Viii ◽  
Phase Iii ◽  
Ovary Cell ◽  
Haemophilia A ◽  
Baby Hamster Kidney

SummaryThis retrospective survey of haemophilia A patients from multiple treatment centres in Ireland assessed the development of inhibitors following a switch in the prescribed treatment from recombinant factor VIII (rFVIII) produced by Chinese hamster ovary (CHO) cells (rFVIII-CHO) to rFVIII produced by baby hamster kidney (BHK) cells (rFVIII-BHK). Ninety-four patients participated in the survey. Most patients (89.4%) had severe haemophilia. One of 77 (1.3%) patients with no inhibitor history developed an inhibitor. This was a patient with moderate haemophilia A who developed a transient, low-titre (1 BU) de novo inhibitor following surgery. Recurrent inhibitors were detected in three of 17 patients with an inhibitor history during the 20-month post-switch study period. All patients continued on rFVIII-BHK therapy, and all tested negative for inhibitors at the time of their last inhibitor assay during the observation period. These results are consistent with the low levels of inhibitor formation demonstrated in phase III studies of previously treated patients receiving BHK-produced rFVIII and support the low risk of inhibitor formation following a change from rFVIIICHO to rFVIII-BHK.

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