title: Pharmacogenetics and the Immunogenicity of Protein Therapeutics.
abstract: The recognition that genetic factors influence the heterogeneity of individual responses to medications with respect to both toxicity and efficacy is not new. However, only following dramatic advances in functional genomics during the last decade did the development of so-called personalized medicine become a realistic possibility. Although drug development approaches that integrate pharmacogenetic information about both the protein drug and its protein target appear logical, given the complexity of biological systems, the selection of appropriate biomarkers and the study design remain daunting tasks. Here we present potential applications of pharmacogenetics in the development of recombinant coagulation factors. In addition, we highlight the potential utility of a personalized approach to predicting and eventually circumventing immunogenicity using the recombinant Factor VIII in the treatment of hemophilia A as a model system. The immunogenicity of protein therapeutics is of increasing concern during the development and licensure of biologics and clearly calls for a pharmacogenetic approach. This is because, with immunogenicity, the predicament is not that all patients develop inhibitory antibodies but that some individuals, ethnicities, or other subpopulations have a stronger immunogenic reaction than others do.
authors.affiliation: Laboratory of Hemostasis, Division of Hematology, Center for Biologics Evaluation and Research , Food and Drug Administration, Bethesda, Maryland.
authors.forename: Gouri S
authors.initials: GS
authors.lastname: Pandey
authors.forename: Zuben E
authors.initials: ZE
authors.lastname: Sauna