chapter  11
12 Pages

Biomarker Strategies in Drug Development: Striking a Balance Between Opportunities and Liabilities

Recent advances in genomics, proteomics, combinatorial chemistry, drug

screening, and other technologies have expanded the number of therapeutic

targets and molecular entities being pursued by scientists in academic,

pharmaceutical/biotechnology, and governmental organizations. The expanded

portfolios of candidate therapeutics and the dramatic growth of research and

development costs relative to growth in sales compel the pharmaceutical and

biotechnology industries to pursue a broad range of strategies to improve their

return on investment [1]. Academic and government researchers and regulatory

authorities are similarly pressured to contain costs while accelerating the delivery

of high-quality public services. Strategic use of biomarkers and surrogate

endpoints represents one approach being promoted to improve productivity in the

discovery, development, and approval of new therapeutics. The Food and Drug

Administration Modernization Act of 1997 (FDAMA ’97) provides legislative

pressure for approval of a new drug product based on a surrogate endpoint that is

reasonably likely, based on epidemiological, therapeutic, pathophysiological,

or other evidence, to predict clinical benefit in otherwise adequate and

well-controlled trials [2]. Moreover, FDAMA ’97 mandates that the Secretary of

the Department of health and Human Services shall “establish a program to

encourage the development of surrogate endpoints that are reasonably likely to

predict clinical benefit for serious or life-threatening conditions for which there

exists significant unmet medical needs”[3]. In response to this challenge, the

FDA partnered with the National Institutes of Health, academia, and the

pharmaceutical and biotechnology industries to identify how this mandate might

be addressed [4]. The result is an intensified far-reaching consideration of how

biomarkers can support drug development and the approval process. This broader

topic has promoted the identification, development, and application of

biomarkers to more effectively address changing public demand, clinical

needs, business environment, and regulatory accountability [5]. With time,

energy, and financial investment, these new partnerships will identify and refine

biomarkers to address the legislative mandate of FDAMA ’97. This chapter

provides background information on biomarker-based research in drug

development and includes (1) key definitions and scope, (2) an overview of

potential opportunities and liabilities related to the use of biomarkers, and (3) a

number of strategies that enable research organizations to maximize the potential

and minimize the liabilities associated with use of biomarkers.