Distinct characteristics of antibody responses against factor VIII in healthy individuals and in different cohorts of hemophilia A patients

Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A

“…Largely transient NNAs were observed in a total of 11 (6.7%) subjects (5 at screening; 6 on study), consistent with or lower than previous reports in the inhibitor-negative hemophilia A population 26,27 and similar to the ;5% observed in the normal population. In a recent longitudinal study of the natural history and significance of NNAs in patients with hemophilia A, individual immune responses to FVIII products were variable over time; however, the clinical impact of NNAs in this study remained unclear.…”

Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease

“…26 The presence of total binding anti-VWF antibodies, antihost cell (CHO) proteins, murine immunoglobulin (Ig)G, and anti-human Furin (total Ig) was determined using a proprietary enzyme-linked immunosorbent assay employing polyclonal anti-human Ig antibodies. 27 Test products rVWF is a purified glycoprotein synthesized in a genetically engineered CHO cell line. 28 The manufacturing process of rVWF is based on a cell culture system that expresses both rFVIII (ADVATE) and rVWF; no exogenously added raw materials of human or animal origin are used in the cell culture and purification processes.…”

AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice

“…We specifically assay for canine IgG2 subclass, which is associated with inhibitory antibody in this HB model on FIX protein concentrate injection or gene therapy, 16,23 and is the equivalent of human IgG4 (the IgG subclass primarily associated with inhibitory antibody 29 ). Although IgG4 is the predominant antibody subclass for human inhibitors, some patients also develop IgG1 and/or IgG2 29 ; therefore, we also assayed for total canine IgG and IgG1. No antibodies of any IgG subclass against cFIX were found in either dog (Figure 1B,E; supplemental Figure 2).…”