Session Speaker

Biomarkers in Targeted-Drug Development for Chronic Inflammatory Diseases
Cornelis L. Verweij
The Netherlands

Targeted therapies using biologicals, such as TNF antagonists, are approved worldwide for the treatment of chronic inflammatory diseases. Despite the success of biologicals in the treatment of chronic inflammatory diseases, clinical experience revealed that not all patients respond equally, and that there are ‘responders’ as well as ‘nonresponders’. Given the destructive nature of chronic inflammatory diseases, the risk of adverse effects and considerable costs for therapy, there is a strong need to make predictions on success before the start of therapy, aiming towards a personalized form of medicine, whereby a specific therapy will be applied that is best suited to an individual patient. The concept of a personalized form of medicine has attracted interest in the field of drug development to implement biomarker strategies to search for molecular and clinical criteria to dissect clinical responders from non-responders.

It is anticipated that implementation of biomarker strategies in drug development will allow:

• Accelerated drug development and reducing cost by utilizing pharmacodynamic and efficacy biomarkers for rational decision making
• Defining enriched populations for clinical trials
• Reducing trial size and number through the use of more clinically relevant biomarker endpoints
• Utilizing safety markers to identify susceptible populations
• Enabling therapeutic drug monitoring
• Delivering companion diagnostics, thereby driving product differentiation

To explain the unresponsiveness of anti-TNF antibodies in the treatment of rheumatoid arthritis, essentially two phases of unresponsiveness might be identified: a primary phase directly after the start of treatment, and a secondary phase that develops in initial responders during the course of therapy. The primary phase of unresponsiveness is oriented on the pharmacodynamic and mechanistic aspects of drug intervention. The latter is explained by the formation of anti-drug antibodies (=anti-anti-TNF antibodies) in a subset of patients.

In this lecture I will address studies related to pharmacodynamic and immunogenicity issues of treatment with TNF-antagonists in RA towards personalized medicine approaches in rheumatoid arthritis.