Anti-Biopharmaceutical Immunization: prediction
and analysis of clinical relevance to minimize the RISK
Executive summary
The introduction of biopharmaceuticals products (BPs) has been a critical step forward in the treatment of many severe diseases. The numbers of BPs (i.e. proteins and monoclonal antibodies) on the market: preparation in progress of diseases treated reflect the success of these molecules, and numerous novel molecules for the treatment of a rapidly expanding number of conditions are anticipated in the next few years.
A major limitation to the use of BPs is the development of anti-drug antibodies (ADA) in a subset of patients. ADA may decrease the efficacy of BPs by neutralizing them or modifying their clearance, and they may be associated with BP-specific hypersensitivity reactions. ADA may also cross-react with closely related endogenous counterparts of BPs thereby compromising important physiological functions. The prediction, prevention and cure of anti-drug (AD) immunogenicity are thus major goals in biopharmaceutical drug development and patient safety.
Many factors contribute to the immunogenicity of BPs. Some are related to the product itself, others to its mode of administration and still others to the underlying disease or the characteristics of patients. Elucidating the significance of these factors and their specific contribution to immunogenicity requires a varied approach including: the development, evaluation and standardization of new tools for predicting and measuring AD immunization, the testing of new concepts originating from basic immunology that have not yet been translated into clinical practice, the development of synthetic predictive models condensing in a comprehensive form all that is known about AD immunization and their validation in a clinical setting. Improvements in our understanding of AD immunization should also lead to the production of guidelines for drug development and the clinical care of patients.