It’s a real paradox: As of March 2014, there were more than 31,850 biomarkers listed in the GOBIOM database (GVK BIO Online Biomarker Database), but only 32 valid genomic biomarkers were included in United States Food and Drug Administration (FDA) approved drug labels. And none of these was a multiplex in vitro diagnostic assay based on proteomic or genomic profiles, an assay that combines the values of multiple variables to yield a single, patient-specific classification, score or index for use in diagnosis or treatment of disease. Clearly, there are lots of biomarker candidates out there, but very few have yet been developed into clinically useful tools.
This is both a challenge and an opportunity, because biomarkers have enormous potential to reshape how oncology drugs are developed and cancer is treated. Biomarkers can be the difference in the eventual approval of new drugs by reducing development time of active compounds, accelerating decision-making about further development of compounds, reducing average development costs, and yielding approved compounds with better patient outcomes. They can help determine whether a drug hits the target and has impact on the biological pathway.
Predictive biomarkers can identify those patients most likely to respond to a therapy or those least likely to suffer an adverse event. Prognostic biomarkers can help predict the course of disease independent of any specific treatment modality, and markers of resistance can identify mechanisms driving acquired drug resistance. Last but not least, biomarkers can be important in telling us why a project fails, helping us formulate the follow-up strategy or trial design and serving to guide drug development, thereby improving the probability of future success.
But to be successful at any of this, it’s become clear that oncology research and development organizations have to commit to a biomarkers strategy very early in development, when targets are first selected. In our view, biomarker strategies need to be embedded in the early development plan for each compound, and clinical trials need to be designed to enable biomarker discovery validation. Waiting to discover predictive biomarkers in Phase 2 or validate them in Phase 3 is simply too late.
Biomarker development also requires insight into disease risk, natural history and outcomes. For that you need deep therapeutic expertise and strategic alignment between discovery, clinical development (including biomarkers and translational medicine) and commercial capabilities.
The work to advance biomarker science offers the promise of more rapid, efficient and economical drug development. The ultimate beneficiaries, however, are patients when biomarkers can be utilized to help produce targeted, precise therapies that have meaningful effects on the course of their cancer, and their lives.