Technology Networks Feature: “Probing the Biomarker Landscape of Human Disease”

Biomarkers can provide invaluable insight into our understanding of human disease, and may be leveraged for both early disease diagnostics and precision medicine approaches. Biomarker discovery, however, can be a challenging and lengthy process, with limited clinical translation. Traditionally biomarker discovery has focused largely on genetic markers using technologies such as next-generation sequencing (NGS). Advances in discovery technologies that look beyond the genome could help to identify biomarkers that enable a more complete understanding of human disease and lead to the development and selection of optimized treatments.

Anna MacDonald (AM): Why is biomarker discovery and validation such an important area?

Dr. Mo Jain (MJ): The cost of bringing drugs to market continues to rise, while the number of new molecular entities that are approved each year continues to drop – despite significant advances in technology and overall computing power. The reality today is that only 1 in 10 drug candidates that enter clinical studies will ever make it to a patient. Most concerning are the high failure rates plaguing later-phase clinical trials, at which point significant time and cost investments have already been made. Seventy percent of drugs entering Phase II and 50% entering Phase III will fail, and a majority of those failures stem from lack of efficacy in the population in which the drug was tested. Even among drugs that do make it through the development pipeline and to patients, we know that only a fraction of individuals experience a positive benefit from the drug’s intended action.

These startling statistics are reflective of the fact that there is often a great deal of heterogeneity within patient populations as well as in human disease. Individuals with the same clinical diagnosis and even the same disease pathology can have very different paths that led them from a normal to a disease state, and as such, respond very differently to any given treatment. Biomarkers allow us to overcome this variability issue, and essentially allow the scientific community to develop and deploy effective drugs faster, more efficiently, and at a lower cost. Biomarkers enhance our understanding of disease by providing readouts of host and disease factors that influence biological processes, disease progression and drug response, enabling us to align a given patient with their specific disease process, and ultimately with the therapeutic they are most likely to respond to and benefit from.

Greater discovery and use of biomarkers in drug programs will transform efficiency, success rates and patient outcomes across complex disease areas. In fact, an analysis of over 20,000 clinical studies encompassing multiple therapeutic areas and clinical agents found that the unifying factor for a drug’s success was whether or not it was developed with a biomarker. Drugs with an associated biomarker have a 2- to 10-fold increase in US Food and Drug Administration approval and a faster approval time. The ultimate value that biomarkers bring is greater understanding of disease to aid diagnosis, prognosis and therapeutic alignment.