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

UNLABELLED

Essentials Discrepancies can exist in factor VIII activity measured by the one-stage or chromogenic assays. LEOPOLD trial data were used to assess clinical impact of BAY 81-8973 potency assignment assay. Efficacy was not affected by the assay used for potency assignment and dosing of BAY 81-8973. Either assay may be used to measure factor VIII activity after BAY 81-8973 infusion.

SUMMARY

Background Product-specific discrepancies have been reported for factor VIII (FVIII) activity determined with one-stage or chromogenic assays. Objective To assess the clinical impact of potency assignment of BAY 81-8973, a full-length, unmodified, recombinant human FVIII, by use of the chromogenic assay or chromogenic assay adjusted to mimic results obtained with the one-stage assay Patients/methods Patients aged 12-65 years with severe hemophilia A received BAY 81-8973 in LEOPOLD I (20-50 IU kg(-1) two or three times weekly [investigator decision]) and LEOPOLD II (randomized to 20-30 IU kg(-1) twice weekly, 30-40 IU kg(-1) three times weekly, or on-demand treatment). Both trials included two 6-month crossover periods in which potency labeling was determined with the chromogenic substrate assay as per the European Pharmacopoeia (CS/EP) or the chromogenic substrate assay adjusted to mimic results obtained with the one-stage assay (CS/ADJ). The annualized bleeding rate (ABR) and FVIII incremental recovery were assessed by the use of pooled data. Results The analysis was perfomed on 121 patients. Median (quartile [Q] 1; Q3) ABRs during the CS/EP and CS/ADJ periods were 1.98 (0; 5.92) and 1.98 (0; 7.34), respectively. The mean incremental recovery was > 2 IU dL(-1) per IU kg(-1) in both periods with the use of either assay for postinfusion FVIII measurements. The median (Q1; Q3) chromogenic/one-stage assay recovery ratio was 1.054 (0.892; 1.150) for the CS/EP period when a plasma standard was used for calibration. Conclusions No impact on the ABR was observed with chromogenic-based as compared with one-stage assay-based potency and dosing. Either assay may be used to determine FVIII plasma activity after infusion of BAY 81-8973 without the need for a product-specific standard.