Chromogenic assay for BAY 81‐8973 potency assignment has no impact on clinical outcome or monitoring in patient samples

Kitchen, Steve; Katterle, Yvonne; Beckmann, H.; Enriquez, Monika Maas

doi:10.1111/jth.13322

Cited by 5 publications

(11 citation statements)

References 33 publications

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“…32 Mean incremental recovery was similar when measured with either assay. 32 Further support for use of either assay was provided in an international comparative laboratory field study, in which 41 laboratories in 11 countries measured BAY 81-8973 levels in spiked plasma samples with the assays routinely used in their laboratory; no clinically relevant differences were found in the ability of laboratories to accurately measure BAY 81-8973 levels using either the one-stage or chromogenic assay. 43 Conclusions BAY 81-8973 is an unmodified, full-length recombinant human FVIII with the same amino acid sequence as rFVIII-FS but with an innovative manufacturing process.…”

Section: Safetymentioning

confidence: 81%

“…No difference in efficacy was demonstrated in this comparison, showing that the difference in potency labeling had no effect on clinical efficacy. 23,24,32 Pharmacokinetics Results from the 26 patients [mean (range) age, 29.5 (12-61) years] in LEOPOLD I with evaluable PK data demonstrated that the PK of BAY 81-8973 was noninferior to, and for some variables superior to, those for rFVIII-FS (Table 1). 15,23,33 Compared with rFVIII-FS, BAY 81-8973 had a significantly longer half-life (geometric mean, 12.2 versus 13.4 h; p = 0.011), higher AUC (1175.7 versus 1397.5 IU•h/dl; p < 0.0001), and slower clearance (0.043 versus 0.036 dl/h/kg; p < 0.0001) based on the one-stage assay; similar differences were seen for PK parameters based on the chromogenic assay.…”

Section: Bay 81-8973 Clinical Evaluationmentioning

confidence: 99%

“…Based on results from LEOPOLD I and II and the pooled analysis, use of the chromogenic assay for potency labeling does not affect the clinical efficacy of BAY 81-8973. 23,24,32 LEOPOLD Kids part A enrolled 51 PTPs aged <12 years (0 to <6 years, n = 25; 6 to <12 years, n = 26). 22 Prophylaxis dosing was determined by the investigator based on the patient's individual requirements.…”

Section: Bay 81-8973 Clinical Evaluationmentioning

confidence: 99%

“…27 Assays for postinfusion monitoring of factor VIII levels Analysis of data from LEOPOLD I and II demonstrated that either the one-stage or chromogenic assay can be used for postinfusion monitoring of FVIII levels in patients treated with BAY 81-8973. 32 Accurate measurements were obtained with either assay using plasma standards for calibration; a product-specific calibration standard is not needed or recommended. 32 Mean incremental recovery was similar when measured with either assay.…”

Section: Safetymentioning

confidence: 99%

“…32 Accurate measurements were obtained with either assay using plasma standards for calibration; a product-specific calibration standard is not needed or recommended. 32 Mean incremental recovery was similar when measured with either assay. 32 Further support for use of either assay was provided in an international comparative laboratory field study, in which 41 laboratories in 11 countries measured BAY 81-8973 levels in spiked plasma samples with the assays routinely used in their laboratory; no clinically relevant differences were found in the ability of laboratories to accurately measure BAY 81-8973 levels using either the one-stage or chromogenic assay.…”

Section: Safetymentioning

confidence: 99%

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BAY 81-8973, a full-length recombinant factor VIII for the treatment of hemophilia A: product review

Mahlangu

Ahuja

Windyga

et al. 2018

Therapeutic Advances in Hematology

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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.

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Section: Safetymentioning

confidence: 81%

Section: Bay 81-8973 Clinical Evaluationmentioning

confidence: 99%

Section: Bay 81-8973 Clinical Evaluationmentioning

confidence: 99%

Section: Safetymentioning

confidence: 99%

Section: Safetymentioning

confidence: 99%

See 3 more Smart Citations

BAY 81-8973, a full-length recombinant factor VIII for the treatment of hemophilia A: product review

Mahlangu

Ahuja

Windyga

et al. 2018

Therapeutic Advances in Hematology

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BAY 81-8973 (Octocog Alfa; Kovaltry®): A Review in Haemophilia A

Keating

2016

BioDrugs

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BAY 81-8973 (octocog alfa; Kovaltry) is an unmodified, full-length, recombinant factor VIII (FVIII) concentrate with the same amino acid sequence as Kogenate FS, but produced with innovative manufacturing technologies. This narrative review discusses the clinical efficacy and tolerability of BAY 81-8973 in haemophilia A, as well as summarizing its pharmacological properties. Results of the LEOPOLD I, LEOPOLD II and LEOPOLD Kids trials demonstrated that routine prophylaxis with intravenous BAY 81-8973 was associated with a low annualized bleeding rate (ABR) in previously treated adult and paediatric patients with severe haemophilia A. In terms of the ABR, BAY 81-8973 prophylaxis was more effective than on-demand treatment. Intravenous BAY 81-8973 was generally well tolerated, with no inhibitor development reported in previously treated patients in the completed LEOPOLD trial programme. In conclusion, BAY 81-8973 is a useful option for prophylaxis and treatment in adult and paediatric patients with haemophilia A.

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Factor VIII and IX assays for post‐infusion monitoring in hemophilia patients: Guidelines from the French BIMHO group (GFHT)

Jeanpierre

Pouplard

Lasne

et al. 2020

European J of Haematology

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Replacement therapy with plasma‐derived or recombinant FVIII and FIX (pdFVIII/pdFIX or rFVIII/rFIX) concentrates is the standard of treatment in patients with haemophilia A and B, respectively. Measurement of factor VIII (FVIII:C) or factor IX (FIX:C) levels can be done by one‐stage clotting assay (OSA) or chromogenic substrate assay (CSA). The French study group on the Biology of Hemorrhagic Diseases (a collaborative group of the GFHT and MHEMO network) presents a literature review and proposals for the monitoring of FVIII:C and FIX:C levels in treated haemophilia A and B patients, respectively. The use of CSA is recommended for the monitoring of patients treated with pdFVIII or rFVIII including extended half‐life (EHL) rFVIII. Except for rFVIII‐Fc, great caution is required when measuring FVIII:C levels by OSA in patients substituted by EHL‐rFVIII. The OSA is recommended for the monitoring of patients treated with pdFIX or rFIX. Large discordances in the FIX:C levels measured for extended half‐life rFIX (EHL‐rFIX), depending on the method and reagents used, must lead to great attention when OSA is used for measuring FIX:C levels in patients substituted by EHL‐rFIX. Data of most of recent studies, obtained with spiked plasmas, deserve to be confirmed in plasma samples of treated patients.

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Chromogenic assay for BAY 81‐8973 potency assignment has no impact on clinical outcome or monitoring in patient samples

Cited by 5 publications

References 33 publications

BAY 81-8973, a full-length recombinant factor VIII for the treatment of hemophilia A: product review

BAY 81-8973, a full-length recombinant factor VIII for the treatment of hemophilia A: product review

BAY 81-8973 (Octocog Alfa; Kovaltry®): A Review in Haemophilia A

Factor VIII and IX assays for post‐infusion monitoring in hemophilia patients: Guidelines from the French BIMHO group (GFHT)

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