Integration of Immunotoxicology Evaluation in Drug Development

During the past 20 years, significant progress has occurred in the fields of basic and clinical immunology which has provided newer, more sensitive methods to assess immune system effects following exposure to chemicals or drugs in humans and laboratory animals. Methods have been selected, optimized, and validated with reference compounds in rodents through several interlaboratory collaborative studies to evaluate the predictive value for detecting toxicity for the immune system of new chemicals and drug candidates. The approach at Sanofi with the evaluation and application of immunotoxicity methods to the preclinical development of new chemical entities (NCEs) (eg, 21 compounds examined) as well as with reference compounds (dexamethasone, cyclophosphamide, and cyclosporin A) is provided. The experience at Sanofi has led researchers there to believe that immunotoxicity endpoints represent another important aspect of safety assessment, can be integrated easily into the drug development process, do not yield a high rate of false positive results, and can be applied on an as needed basis. These evaluations can be driven by data suggestive of an immune effect, the drug's indication, and the class of the chemical being evaluated (eg, anti-AIDS NCE) or systematically performed.