The 2nd International Conference on Drug Discovery & Therapy: Dubai, February 1 - 4, 2010


Biomarkers in targeted-drug development for chronic inflammatory diseases

Targeted therapies using biological, such as TNF antagonists, are approved worldwide for the treatment of chronic inflammatory diseases. Despite the success of biological 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:
  1. Accelerated drug development and reducing cost by utilizing pharmacodynamic and efficacy biomarkers for rational decision making
  2. Defining enriched populations for clinical trials
  3. Reducing trial size and number through the use of
    4. more clinically relevant biomarker endpoints
  4. Utilizing safety markers to identify susceptible populations
  5. Enabling therapeutic drug monitoring
  6. 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.


Cornelis L. Verweij
VU University Medical Center
Amsterdam, The Netherlands

 

Cornelis L. Verweij (b. 1956) received his PhD in 1987 from the University of Amsterdam on his studies on the cloning and biosynthesis of von Willebrand factor (vWF). After completion of his PhD-study he was awarded a 2 year EMBO-long term fellowship to study the effect of the immune suppressive drug Cyclosporin A on IL-2 gene regulation in the lab of Professor Gerald R. Crabtree at Stanford University. He continued to work on IL-2 gene regulation in the Netherlands at the Central Laboratory of the Red Cross (CLB) in Amsterdam. In 1991 he joined the faculty of the Leiden University Medical Center, where he studied T-cell biology, and the functional aspects of cytokine genetics in relation to auto-immune diseases, in particular rheumatoid arthritis. As a recipient of a Fulbright award he gained extensive experience in genomic profiling studies during a sabbatical year in the lab of Professor Patrick O. Brown at Stanford University. Since 2001 he is professor of Molecular Biology and Biochemistry at the VU University medical center (VUmc) in Amsterdam.

Prof Verweij’s major area of research interest is on biomarker discovery studies in chronic inflammatory diseases. He and his colleagues operate a systems biology science program in which state-of-the-art genomics and proteomics techniques are applied to identify biomarkers for diagnosis, patient stratification and therapy responsiveness, and to elucidate the biological pathways that underlie inflammatory diseases, aimed at defining novel drug targets, and early diagnosis, and preventive- and personalized medicine. From Sept. 2005 till Sept. 2007 he was also employed as head of Immunology/Biomarker Development at Novartis Pharma AG in Basel, Switzerland, where he developed and applied biomarker strategies in clinical development programs in Immunology.

He is an author on more than hundred publications in the field of biomedical research. He is Editor-in-chief “The Open Rheumatology Journal” and a member of the editorial board of “Genes & Immunity” and, serves on several national and international scientific committees and review boards.
 
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