Pharmacogenetics in drug development

Abstract

Over the last two decades, identification of polymorphisms that influence human diseases has begun to have an impact on the provision of medical care. The promise of genetics lies in its ability to provide insights into an individual's susceptibility to disease, the likely nature of the disease and the most appropriate therapy. For much of its history, pharmacogenetics (PGx-the use of genetic information to impact drug choice) has been limited to comparatively simple phenotypes such as plasma drug levels. Progress in genetics technologies has broadened the scope of PGx efficacy and safety studies that can be implemented, impacting on a broad spectrum of drug discovery and development activities. Recent PGx data show the ability of this approach to generate information that can be applied to dose selection, efficacy determination and safety issues. This in turn will lead to significant opportunities to affect both the approach to clinical development and the probability of success--the latter being an important aspect for pharmaceutical companies and for the patients who will benefit from these new medicines.

Figure 1

A typical graph of serum concentration versus time for individual study subjects.

Figure 2

Graph of weight loss in the whole (ITT) study group versus weight loss in the genotype-selected (PGx) group.

Figure 3

Histogram showing weight change during an eight week obesity study.

Figure 4

Association analysis of bilirubin levels versus phenotype in tranilast treated subjects.