New biological therapeutics exhibit a large variety of formats which may diverge from human proteins. This increased complexity may cause unwanted immunogenicity affecting the efficacy, safety, and pharmacokinetics of these new biological entities. Anti-Drug Antibodies (ADAs) developed in preclinical species are not predictive for immunogenicity in humans and may be overlooked in small populations in early clinical trials. A clear picture of the impact of ADAs on efficacy and safety of drugs may be evident in a larger population in Phase III only, resulting in the failure of late-stage programs with negative consequences for both patients and sponsors. Therefore, assessing the risk of immunogenicity in early discovery phases and consequential mitigation strategies are essential for preventing issues in the clinic.
A plethora of different in silico and in vitro tools are available to evaluate potential immunogenicity: improper applications and interpretations may lead to overprediction of immunogenicity, or vice versa, to unforeseen risks. At EMD Serono, we have established a workflow to ensure an appropriate evaluation: the immunogenicity risk assessment and an in silico analysis, which in turn may trigger the implementation of in vitro assays. This streamlined approach is used to reduce the number of molecules tested with in vitro assays that are costly and low-throughput. Further, it can be applied as a screening tool for hits, as well as for selecting the less immunogenic format for novel biotherapeutics. The final data package, including both the in silico and as needed in vitro results, will drive the initial risk assessment for immunogenicity, and subsequent mitigation strategy for the potential risk for patients.
Learning Objectives:
Recognize the value of a streamlined workflow for the preclinical evaluation of immunogenicity
Judge the impact of in vitro tools for immunogenicity assessment
Implement their immunogenicity strategy for biotherapeutics
