Preclinical Immunogenicity Assessment of Baxter‘s Recombinant Factor VIIa,

Abstract 3327

Baxter has developed a recombinant FVIIa (rFVIIa) product for the treatment of hemophilia patients with factor VIII or factor IX inhibitors. Before entering clinical development we assessed the immunogenic safety profile of the new product candidate BAX 817 using two novel mouse models that mimicked specific aspects of the situation in patients.

Several comparative preclinical immunogenicity studies were conducted to assess the immunogenicity profile of Baxter`s rFVIIa BAX 817 in comparison to a licensed recombinant FVIIa product. Three different mouse models were used for this purpose. The first model expresses specific immune tolerance against human FVIIa and, therefore, mimics the situation in both hemophilia A and hemophilia B patients. Using this model, we asked if Baxter‘s rFVIIa is able to maintain immune tolerance to human FVIIa.

The second model is a hemophilia A model that mimics the situation in an important fraction of hemophilia A patients with FVIII inhibitors. This model expresses a human MHC-class II haplotype (HLA-DRB1*1501) that was previously shown to be associated with an increased risk for the development of FVIII inhibitors.

The third model represents a normal wildtype C57BL/6 mouse.

All mice were treated with 8 weekly doses of either Baxter‘s rFVIIa BAX 817 or a licensed recombinant FVIIa product. Total anti-FVIIa antibodies were analyzed prior to the first dose as well as after the 4^th and the 8^th dose using ELISA assays.

Baxter`s rFVIIa BAX 817 and a licensed recombinant FVIIa product induced similar titers of anti-FVIIa antibodies in C57BL/6 wildtype mice and in hemophilic HLA-DRB1*1501 mice. In addition, both Baxter`s rFVIIa BAX 817 and a licensed recombinant FVIIa product were able to maintain specific immune tolerance in a novel mouse model that is immunologically tolerant to human FVIIa.

Based on the data obtained we conclude that both Baxter‘s rFVIIa BAX 817 and a licensed recombinant FVIIa product have a comparable immunogenic safety profile.