Significance of Biomarkers in Drug Development

Understanding the molecular basis of disease will limit failure in drug development due to wrong biological hypotheses. Most of the emphasis on biomarkers in drug development is on early identification of potentially successful molecules to predict potential efficacy and safety. However, it is important that biomarkers be chosen, developed and evaluated in a way that enables them to provide confidence to terminate a molecule when it has no effect on the biomarker. This is clearly a challenge for novel molecules that are the first in their class, but it can be achieved through building a sound theoretical rationale for the biomarker supported by evidence of linkage to the effect of the drug in appropriate animal models. It is worthwhile to develop biomarkers for exploring the pharmacology of new molecules as well as to develop potential biomarkers of efficacy. A molecule that does not have the intended pharmacological effect is unlikely to have the desired efficacy and its development should be terminated. Discovery efforts would then be directed at understanding the reasons for the lack of pharmacological effect and finding improved molecules. For those molecules that have the intended pharmacological effect but then fail to show efficacy, it is possible to say with confidence that the molecular target is ineffective and that discovery effort should be directed to other targets. Such an approach will increase the overall success rates of the candidate molecules delivered into clinical development.

Pharmacogenomic Biomarker Information in Drug Labels

A review of 1200 drug labels of FDA-approved drugs in the US from 1945 to 2005 revealed that 121 contained pharmacogenomic information: 69 referred to human genomic biomarkers, and 52 referred to microbial genomic biomarkers. Of the labels referring to human biomarkers, 43 (62%) pertained to polymorphisms in cytochrome P450 enzyme metabolism, with CYP2D6 being most common. Of 36.1 million patients whose prescriptions were processed by a large pharmacy benefits manager in 2006, about 8.8 million, i.e. approximately one fourth, received one or more drugs with human genomic biomarker information in the drug label (Frueh et al. 2008). The study concluded that incorporation and appropriate use of pharmacogenomic information in drug labels should be tested for its ability to improve drug use and safety in the US. The number of drugs with pharmacogenomic information in labels is increasing.

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