scholarly journals BAY 81-8973, a full-length recombinant factor VIII: manufacturing processes and product characteristics

Haemophilia ◽  
2016 ◽  
Vol 23 (2) ◽  
pp. e67-e78 ◽  
Author(s):  
S. Garger ◽  
J. Severs ◽  
L. Regan ◽  
A. Hesslein ◽  
J. Ignowski ◽  
...  
Keyword(s):  
Factor Viii ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Manufacturing Processes ◽  
Product Characteristics

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.

Quantitative Evaluation of Factor VIII in Factor VIII Products.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4012-4012
Author(s):  
Saulius Butenas ◽  
Behnaz Parhami-Seren ◽  
Matthew T. Gissel ◽  
Edward D. Gomperts ◽  
Kenneth G. Mann
Keyword(s):  
Factor Viii ◽  
Protein Content ◽  
Quantitative Evaluation ◽  
Hemophilia A ◽  
Specific Activity ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Factor Viii Activity

Abstract Several factor VIII products, recombinant and natural, have been used for hemophilia A treatment worldwide. Typically, two activity-based assays (factor Xase and aPTT) are used for the assessment of factor VIII concentration in these products. Frequently, the results are dependent upon the assay and its modifications in different laboratories. In this study, we evaluated five pharmacologic factor VIII products (three lots of each) in three activity-based assays and in two immunoassays for the concentration and activity of factor VIII protein. Two factor VIII products were plasma-derived (Immunate and Hemofil M) and three were recombinant; two of these contained full-length factor VIII (Recombinate and Kogenate) and one was B-domainless (ReFacto). Albumin-free full-length recombinant factor VIII was used as a standard in all assays. In the factor Xase assay, all recombinant factor VIII products and Immunate at 1U/ml (indicated by manufacturer) showed activity similar to that of 0.7nM (1U/ml) standard, whereas activity of Hemofil M was 64–68% of the standard. In the aPTT assay both full-length recombinant products and Hemofil M displayed activity similar to the standard, whereas Immunate had increased (142% of standard) and ReFacto decreased (83% of standard) activity. In synthetic plasma, all three recombinant products had standard-like activity, whereas Hemofil M and Immunate were slightly more active than standard. The ELISA immunoassay revealed that the factor VIII protein content in Recombinate, Kogenate and Hemofil M corresponded to the units assigned by manufacturers (1.4–1.6x1012U/mol vs1.4x1012U/mol calculated for standard), whereas the specific activity of Immunate was 50% of that expected (0.7x1012U/mol). In contrast, the specific activity of ReFacto was almost 3-fold that of full-length factor VIII (4.0x1012U/mol). The data of this study indicate that: 1) factor VIII activity estimated in different assays gives dissimilar results; 2) the specific activity of factor VIII in various factor VIII products is different and, as a consequence, administration of an equal factor VIII activity in U/ml means the administration of different amounts of factor VIII protein.

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.

scholarly journals BAY 81‐8973, a full‐length recombinant factor VIII : results from an International comparative laboratory field study

Haemophilia ◽  
2016 ◽  
Vol 22 (3) ◽  
Author(s):  
S. Kitchen ◽  
H. Beckmann ◽  
Y. Katterle ◽  
S. Bruns ◽  
D. Tseneklidou‐Stoeter ◽  
...  
Keyword(s):  
Factor Viii ◽  
Field Study ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
International Comparative
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