6 - Immunogenicity assessment of PEGylated proteins, Lonquex, a PEGylated G-CSF case study

Abstract

PEGylation is a well-established approach to extend the half-life of therapeutic proteins. This chapter illustrates a strategy for immunogenicity assessment of PEGylated proteins, using Lonquex (lipegfilgrastim), a long-acting recombinant granulocyte colony-stimulating factor (G-CSF), as an example. The clinical immunogenicity of Lonquex was analyzed in two clinical trials. The strategy for immunogenicity assessment was based on sequential assays for screening, confirmation, antibody titer, neutralizing antibody, and binding specificity characterization of antidrug antibody (ADA). Among 255 breast cancer patients receiving Lonquex, the incidence of treatment-emergent ADA was low (phase 2: 1.3%; phase 3: 1.0%). None of the treatment-emergent ADA-positive samples exhibited neutralizing activity against Lonquex or the native G-CSF. No changes were observed in neutropenia-related efficacy measures among ADA-positive patients and no treatment-related hypersensitivity or anaphylaxis occurred. Using this testing strategy, the results indicate that there is low immunogenicity and no apparent impact of ADA on Lonquex efficacy and safety.