The drug discovery process is currently flawed at both pre-clinical and clinical levels. Biomarkers are an emerging “bridge over troubled waters” between these two areas, and a solution for their respective ills.
Preclinically, gene expression networks, not single gene products, need to be targeted for comprehensive and successful treatment of diseases. Combinations of drugs need to be developed and used from the beginning for broad impact. Profiling baseline gene expression and response to drugs in animal models using biomarkers can ensure the right combinations of drugs are selected and advanced towards clinical testing.
Clinically, one size does not fit all. The blockbusters of the future will not be blockbusters in terms of patient population sizes treated, but rather due to precision and efficacy, commanding a deserved premium price that way. Some of the same biomarkers derived from discovery work and pre-clinical studies can be used in clinical studies, providing solutions for their current limitations: better diagnosis and patient stratification, objective monitoring of response to treatment, and a handle on the placebo effect. Early biomarker information from clinical trials will provide in an iterative fashion intelligence for improved selection criteria and outcomes in later clinical trials, leading to an enhanced rate of successfully approved medications, albeit for more narrow indications.
Alexander B. Niculescu, III, MD, PhD