BAY 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.