Clinical pharmacology of immuno-modulatory biotherapeutics : innovations in early drug development

Abstract

Currently, a large number of pharmaceutical companies focus on the development of (immunomodulatory) biotherapeutics such as recombinant proteins and monoclonal antibodies, developed for therapeutic and diagnostic purposes. The development of these biotherapeutics is challenging, among others due to a lack of robust efficacy data when administered to patients. Hence, the identification of selective, early phase biomarkers is particularly needed in their process of development. By the identification of these biomarkers (for instance using in vivo or ex vivo challenge models), question-based drug development together with the performance of concurrent engineering provides the opportunity to collect and connect data already in the early stages of drug development resulting in an earlier assessment of the potential value of a new (biotherapeutic) compound and a potential increase in the drug development success rates. This thesis provides an extended overview of different types of clinical pharmacology studies concerned with the complicated investigation of immunomodulatory biotherapeutics in the early stage of drug development. Key factors herein are the search for selective biomarkers in healthy volunteers and patients, the development of new methods, and optimization of existing methods to improve and potentially accelerate the development process of immunomodulatory biotherapeutics.