Biomarker Analysis as a Decision-Making Tool in Drug Discovery and Development

Abstract

Biomarkers are measurable properties that reflect the pathophysiology of disease, mechanism of action of a molecule or the interaction between the two. The early implementation of a biomarker strategy within drug development offers a great opportunity to enhance the efficiency of drug development. More specifically, biomarkers may be used to aid in lead compound selection, dose focusing, patient stratification and defining the mechanism of action of novel therapeutics. Validated biomarkers, especially surrogate endpoints, may have broader utility in both a regulatory context and in clinical practice. Biomarkers may be used to evaluate both the safety and efficacy of new drugs. Biomarker identification is enhanced with a clear understanding of the steps involved in a pathophysiology cascade. Biomarkers discovered with the aid of molecular profiling may have particular utility in approaching complex diseases with poorly characterised pathophysiology, as in type 2 diabetes mellitus. For example, expression profiling experiments enabled the discovery of the 30kD protein adiponectin — a specific biomarker for in vivo activation of peroxisome proliferator-activator receptor gamma (PPARψ) activity. Adiponectin offers great utility in short-term clinical studies in healthy volunteers or patients with type 2 diabetes to assess whether new potential PPAR? agonists are efficacious in humans. In addition to enlightening key underlying pathophysiology, biomarkers such as adiponectin allow for improved decision-making earlier in development. Ultimately biomarkers can be used to optimise development efficiency from discovery through to registration.