Translational drug discovery and development with the use of tissue-relevant biomarkers: towards more physiological relevance and better prediction of clinical efficacy.

Authors:
P Florian
P Florian
Freie Universität Berlin
Germany
E Bartnik
E Bartnik
University of Warsaw
Poland
M Herrmann
M Herrmann
Universitätsklinikum des Saarlandes
Germany

Exp Dermatol 2019 Apr 16. Epub 2019 Apr 16.

Sanofi, Global Head of Immunology Therapeutic Research Area, 640 Memorial Drive, Cambridge, MA, 02139, USA.

Due to the clinical development of drugs such as secukinumab, ustekinumab and dupilumab, major changes have been achieved in the treatment of patients diagnosed with psoriasis and atopic dermatitis. In academia and the pharmaceutical industry, research is increasingly moving towards the development of bi-specific antibodies and multi-specific nanobodies, as there is a compelling need for new treatment modalities for patients suffering from auto-immune or malignant disease. The purpose of this review is to discuss aspects of translational drug development with a particular emphasis on indications such as psoriasis and atopic dermatitis. The identification of biomarkers, the assessment of target organ pharmacokinetic and pharmacodynamics interactions and a wide range of in-vitro, ex-vivo and in-vivo-models should contribute to an appropriate prediction of a biological effect in the clinical setting. As human biology may not be perfectly reflected by approaches such as skin equivalents or animal models, novel approaches such as the use of human skin and dermal microperfusion assays in healthy volunteers and patients appear both reasonable and mandatory. These models may indeed generate highly translationally relevant data that have the potential to reduce the failure rate of drugs currently undergoing clinical development. This article is protected by copyright. All rights reserved.

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Source
https://onlinelibrary.wiley.com/doi/abs/10.1111/exd.13942
Publisher Site
http://dx.doi.org/10.1111/exd.13942DOI Listing
April 2019
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