Biomarkers and Drug Development
Jeffrey S. Ross, M.D.
Senior Scientific Advisor Prous Science
Abstract
Today, an increasingly educated public using the internet and other resources are demanding more and more information about the specific forms of their diseases and how those ailments might be arrested or cured with new therapies custom-designed for their individual clinical status. Biomarkers can be defined as a series of gene sequences and mutations, mRNA expression profiles, tissue proteins and blood-based tests that can be used to detect the predisposition for disease, screen for its presence, confirm its diagnosis, assess its severity, predict its response to available therapies and monitor its clinical course. Biomarkers, including pharmacodynamic, pharmacogenetic, pharmacogenomic, toxicogenomic and metabonomic assays now also play integral roles in the discovery, development and regulatory approval of new drug products. At the start of the 21st century, the routine and molecular diagnostic industries have grown at a double-digit pace to meet increasing demands for the integration of biomarker-based diagnostic tests with the selection of therapy and the transition to truly personalized medicine. In cancer drug development, a wide variety of drugs are at various stages of preclinical, early and late clinical development that are targeted to tumor-specific gene and protein signatures in the tumors. These combination products may ultimately require co-approval of the drug and diagnostic test by the regulatory agencies. Despite initial concerns that this drug – test combination approach would segment the market by reducing the number of patients eligible for treatment and lower the economic value of the drug, the commercial success of agents such as imatinib and trastuzumab have alerted the pharmaceutical industry as to the potential value of “biomarker-guided” drugs. In addition, new evidence continues to emerge showing how the early institution of biomarker-based assays can more reliably predict both efficacy and toxicity in the preclinical and early clinical phases of drug development. This can allow both for improved success rates in the selection of compounds to move forward and for cost savings associated with an earlier cessation of the studies of novel compounds destined to fail.
With the above statements in mind, it becomes clear that the creation of a broad database of disease-specific biomarkers that includes their biologic basis and their drug development - clinical uses and limitations would be a significant asset for any pharmaceutical and biotechnology organization interested in both speeding up the rate and reducing the cost of the development of their future products.
