Translatability scoring in drug development: eight case studies
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RESEARCH
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Translatability scoring in drug development: eight case studies Alexandra Wendler and Martin Wehling*
Abstract Translational medicine describes the transfer of basic in vitro and in vivo data into human applications. In the light of low rates of market approvals for new medical entities, better strategies to predict the risk of drug development should be used to increase output and reduce costs. Recently, a scoring system to assess the translatability of early drug projects has been proposed. Here eight drugs from different therapeutic areas have been subjected to a retrospective test-run in this system fictively located at the phase II-III transition. The scores gained here underline the importance of biomarker quality which is pivotal to decrease the risk of the project in all cases. This is particularly evident for gefitinib. The EGFR mutation status is a breakthrough biomarker to predict therapeutic success which made this compound clinically acceptable, and this is plausibly reflected by a considerable increase of the translatability score. For psychiatric and Alzheimer’s drugs, and for a CETP-inhibitor, the lack of suitable biomarkers and animal models is reflected by a low translatability score, well correlating with the excessive translational risk in these areas. These case studies document the apparent utility of the scoring system, at least under retrospective conditions, as the scores correlate with the outcomes at the level of market approval. Prospective validation is still missing, but these case studies are encouraging. Keywords: Dabigatran, Ipilimumab, Gefitinib, Vilazodone, Latrepirdine, Semagacestat, Translatability Score, Translational medicine, Drug development
Introduction Translational medicine is an important component of drug development and describes the conditions and prerequisites for the transfer of in vitro and in vivo findings into human applications [1], and should ultimately facilitate the development of new drugs. It is hoped that the “empty pipeline syndrome” (lack of innovation in drug industry, exceptions granted, e.g. oncology) could be treated by this (and other) means and the sequelae of the “patent cliff” (an estimated loss of 150 billion USD per year in turnover of big pharma companies by patent expiration within 2-3 years) attenuated. In the process of drug development several checkpoints can be used to evaluate the probable translational success of a drug project. In 2009 a proposal for the scoring of the translatability of an early drug project was presented [2]. The score assesses the availability and * Correspondence: [email protected] Institute of Experimental and Clinical Pharmacology and Toxicology Clinical Pharmacology Mannheim, Faculty of Medicine Mannheim, Ruprecht-KarlsUniversity of Heidelberg, Maybachstr.14, D-68169 Mannheim, Germany
quality of in vitro and in vivo results, clinical data, biomarkers, and personalized medicine aspects. The weights given to these different aspects reflect the particular importance in
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