Lack of immune response to mouse IgG in hemophilia A patients treated chronically with Monoclate®, a monoclonal antibody affinity purified factor VIII preparation

Hemophilia A is caused by factor VIII deficiency that historically has been treated with either a cryoprecipitate fraction of serum or factor VIII concentrate. Recently, the availability of affinity isolated factor VIII (Monoclate®) has allowed for a highly purified preparation for the chronic therapy of hemophilia A. This factor VIII preparation contains a trace quantity (< 50 ng/100 I.U.) of mouse IgG. Immunoassays for the measurement of human IgG, IgM and IgE anti-mouse IgG antibody (HAMA) were developed and used to measure HAMA levels in hemophilia A patients undergoing chronic therapy with Monoclate® in three different clinical studies. Natural antibodies to mouse IgG were observed in patient sera prior to Monoclate® infusion. Data is presented demonstrating that induction of HAMA upon Monoclate® treatment does not occur. The low level of mouse IgG contained in Monoclate® appears to be below the threshold of immunogenicity. Most importantly, clinical symptoms related to hypersensitivity or anaphylaxis were never observed in any patient undergoing chronic therapy with Monoclate® in these clinical studies.