1,722,568 research outputs found
Matching-adjusted indirect comparisons of efficacy of BAY 81-8973 vs two recombinant factor VIII for the prophylactic treatment of severe hemophilia A
No full textJennifer Pocoski,1 Nanxin Li,2 Rajeev Ayyagari,2 Nikki Church,1 Monika Maas Enriquez,1 Quer Xiang,2 Sneha Kelkar,3 Ella X Du,2 Eric Q Wu,2 Jipan Xie3 1Bayer HealthCare Pharmaceuticals, Whippany, NJ, 2Analysis Group, Inc., Boston, MA, 3Analysis Group, Inc., New York, NY, USA Background: No head-to-head trials comparing recombinant factor VIII (rFVIII) products currently exist. This was a matching-adjusted indirect comparison (MAIC) study of efficacy of BAY 81-8973 with antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM) and turoctocog alfa for the prophylaxis of severe hemophilia A. Methods: A systematic literature review was conducted to identify trials of rAHF-PFM and turoctocog alfa. Comparisons were conducted using BAY 81-8973 individual patient data (IPD) from LEOPOLD trials and published data from rAHF-PFM and turoctocog alfa trials. Differences in outcome reporting were reconciled using transformation of BAY 81-8973 IPD. Patients in pooled LEOPOLD trials were weighted to match baseline characteristics for rAHF-PFM or turoctocog alfa trials using MAICs. After matching, annualized bleed rates (ABRs) were compared using weighted t-tests. Results: Two rAHF-PFM trials and one turoctocog alfa trial were identified. In these trials, rFVIIIs were dosed thrice weekly or every other day; in LEOPOLD trials, BAY 81-8973 was dosed twice- or thrice weekly. Three MAICs were conducted because the two rAHF-PFM trials calculated ABRs differently, matching for age, race, and weight (turoctocog alfa only). BAY 81-8973 had similar ABR of all bleeds vs rAHF-PFM (two trials: 4.8 vs 6.3, 1.9 vs 1.8 [square root transform]) and lower ABR of spontaneous bleeds and trauma bleeds (2.6 vs 4.1, 2.1 vs 4.7; both P<0.05). BAY 81-8973 showed lower ABR of all bleeds and spontaneous bleeds vs turoctocog alfa (4.3 vs 6.5, 2.8 vs 4.3; both P<0.05) and similar ABR of trauma bleeds (1.5 vs 1.6). In subgroup analysis, twice-weekly BAY 81-8973 had similar ABRs of all bleeds, spontaneous bleeds, and trauma bleeds compared to rAHF-PFM and turoctocog alfa. Conclusion: This indirect comparison found that prophylaxis with BAY 81-8973, even including the lower frequency of two times a week and lower factor VIII consumption, has efficacy comparable to rAHF-PFM and turoctocog alfa, which were dosed thrice weekly or every other day. The use of IPD enabled adjustments for differences in calculation of ABRs and population characteristics between trials. Keywords: hemophilia A, BAY 81-8973, rAHF-PFM, turoctocog alfa, MAIC, annualized bleed rat
Despacho n. 8973 de 2 de setembro de 2014
No full textAverbação de tempo de serviço. Processo STJ n. 8973/2014
BAY 81-8973, a full-length recombinant factor VIII for the treatment of hemophilia A: product review
No full text BAY 81-8973 (Kovaltry®) is an unmodified, full-length recombinant factor VIII (rFVIII) approved for the prevention and treatment of bleeding episodes in patients with hemophilia A. The amino acid sequence for BAY 81-8973 is identical to that of sucrose-formulated rFVIII (rFVIII-FS; Kogenate® FS/KOGENATE®, Bayer), but the two products differ in their manufacturing approaches. The manufacture of BAY 81-8973 includes several modifications and enhancements, such as the introduction of the gene for human heat shock protein 70, a molecular chaperone protein that facilitates folding of proteins; no addition of human- or animal-derived proteins in the cell culture, purification process, or final formulation; and use of a 20-nm filter to remove any potential aggregates and pathogens. BAY 81-8973 was extensively studied in the LEOPOLD clinical development program, which enrolled participants of all age groups (children, adolescents, and adults) with severe hemophilia A. The pharmacokinetic profile of BAY 81-8973 was shown to be noninferior to, and for some variables more favorable than, rFVIII-FS and another commercial full-length rFVIII product. BAY 81-8973 was shown to be efficacious when used for prophylaxis, on-demand treatment, and perioperative hemostasis. The efficacious prophylaxis dose of BAY 81-8973 was approximately 20–40 IU/kg given two or three times per week, which achieved low annualized bleeding rates. Either the one-stage or the chromogenic assay provides accurate measurements for postinfusion monitoring of BAY 81-8973 levels, with no product-specific calibration standard needed. The incidence of treatment-related adverse events was ⩽7% across all LEOPOLD studies, and no previously treated patient developed anti-BAY 81-8973 inhibitors in the completed primary studies. </jats:p
Linked collectors and determiners for: ZFMK Araneae collection.
No full textNatural history specimen data linked to collectors and determiners held within, "ZFMK Araneae collection". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/64a2315f-b454-450b-8973-25ddc62d16b4">https://bionomia.net/dataset/64a2315f-b454-450b-8973-25ddc62d16b4</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/64a2315f-b454-450b-8973-25ddc62d16b4">https://gbif.org/dataset/64a2315f-b454-450b-8973-25ddc62d16b4</a>. Formatted as a Frictionless Data package
Increased branching and sialylation of N-linked glycans correlate with an improved pharmacokinetic profile for BAY 81–8973 compared with other full-length rFVIII products
No full textJohn M Teare,1 David S Kates,1 Anita Shah,2 Stephen Garger1 1Biological Development, Bayer US LLC Pharmaceuticals, Berkeley, CA, USA; 2Pharmacokinetics Pharmacodynamics Hematology, Bayer US LLC Pharmaceuticals, Whippany, NJ, USA Background: BAY 81–8973 (Kovaltry) is an unmodified full-length recombinant factor VIII (rFVIII) for treatment of hemophilia A. The BAY 81–8973 manufacturing process results in a product of enhanced purity with a consistently high degree of branching and sialylation of N-linked glycans. This study evaluated whether a relationship exists between N-linked glycosylation patterns of BAY 81–8973 and two other rFVIII (sucrose-formulated rFVIII [rFVIII-FS; Kogenate FS]) and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM; Advate) and their pharmacokinetic (PK) characteristics.Materials and methods: N-linked glycans or terminal carbohydrates were enzymatically removed from immobilized BAY 81–8973, rFVIII-FS, and rAHF-PFM proteins and analyzed using high-performance liquid chromatography to determine the percentage of individual N-linked glycan structures and degree of sialylation of each structure. PK data were available from two separate phase 1 crossover studies in which the PK profile of BAY 81–8973 was compared with that of rFVIII-FS (n=26) and rAHF-PFM (n=18) in patients with severe hemophilia A who received a single 50 IU/kg dose of each product.Results: BAY 81–8973 and rFVIII-FS had increased N-linked glycan branching with higher levels of sialylation compared with rAHF-PFM. Levels of trisialylated glycans were 29.0% for BAY 81–8973 vs 11.5% for rFVIII-FS and 4.8%–5.5% for rAHF-PFM; tetrasialylated glycans were 12.0% vs 2.8% and 0.6%, respectively. Degree of sialylation was 96% for BAY 81–8973, 94% for rFVIII-FS, and 78%–81% for rAHF-PFM. Based on chromogenic assay results from the single-dose phase 1 PK studies, BAY 81–8973 half-life was 15% longer than that for rFVIII-FS and 16% longer than rAHF-PFM.Conclusion: Increased N-glycan branching and sialylation were seen for BAY 81–8973 vs rFVIII-FS and rAHF-PFM. Improved PK for BAY 81–8973 relative to rFVIII-FS and rAHF-PFM as seen in single-dose crossover PK studies might be related to this greater level of branching and sialylation, which can prolong the time BAY 81–8973 remains in the circulation. Keywords: clearance, glycan structure, glycosylation, half-life  
BAY 81-8973 prophylaxis and pharmacokinetics in haemophilia A: Interim results from the TAURUS study
No full textAbstract: Objectives To report interim data from TAURUS, a study assessing real-world prophylactic treatment with unmodified, full-length recombinant FVIII BAY 81-8973 (Kovaltry(R); Bayer) indicated for haemophilia A. Methods TAURUS (NCT02830477) is an international, open-label, prospective, non-interventional, single-arm study with a one-year observation period (target N = 350). Patients have moderate or severe haemophilia A (FVIII = 50 exposure days to any FVIII product. Clinician- and patient-reported outcomes are captured on previous product use, changes in prophylaxis dose and dosing frequency, FVIII consumption, reported bleeding rates, treatment satisfaction and adherence, pharmacokinetic (PK) data (if available) and safety data. Results At cut-off, baseline data were available from 160 patients (89 had >= 6 months of follow-up data). Most patients had severe haemophilia A (85%), infused BAY 81-8973 >= 3x/wk (59%) and experienced a median number of total bleeds of 2.0 (non-annualised; 246 days median documentation period). Good levels of treatment satisfaction (Hemo-SAT(A,P)) and adherence (VERITAS-Pro) were maintained. TAURUS demonstrated a favourable PK profile of BAY 81-8973 in comparison with other standard half-life rFVIIIs and supported the WAPPS PopPK model. No patients developed inhibitors. Conclusions TAURUS data demonstrate effective prophylaxis with BAY 81-8973 in the real world without compromising patient satisfaction or adherence
BAY 81-8973, a full-length recombinant factor VIII: Human heat shock protein 70 improves the manufacturing process without affecting clinical safety
No full textAbstractBAY 81-8973 is a full-length, unmodified recombinant human factor VIII (FVIII) approved for the treatment of hemophilia A. BAY 81-8973 has the same amino acid sequence as the currently marketed sucrose-formulated recombinant FVIII (rFVIII-FS) product and is produced using additional advanced manufacturing technologies. One of the key manufacturing advances for BAY 81-8973 is introduction of the gene for human heat shock protein 70 (HSP70) into the rFVIII-FS cell line. HSP70 facilitates proper folding of proteins, enhances cell survival by inhibiting apoptosis, and potentially impacts rFVIII glycosylation. HSP70 expression in the BAY 81-8973 cell line along with other manufacturing advances resulted in a higher-producing cell line and improvements in the pharmacokinetics of the final product as determined in clinical studies. HSP70 protein is not detected in the harvest or in the final BAY 81-8973 product. However, because this is a new process, clinical trial safety assessments included monitoring for anti-HSP70 antibodies. Most patients, across all age groups, had low levels of anti-HSP70 antibodies before exposure to the investigational product. During BAY 81-8973 treatment, 5% of patients had sporadic increases in anti-HSP70 antibody levels above a predefined threshold (cutoff value, 239 ng/mL). No clinical symptoms related to anti-HSP70 antibody development occurred. In conclusion, addition of HSP70 to the BAY 81-8973 cell line is an innovative technology for manufacturing rFVIII aimed at improving protein folding and expression. Improved pharmacokinetics and no effect on safety of BAY 81-8973 were observed in clinical trials in patients with hemophilia A
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