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Biomarkers could be a boon for a new era of medicine.

Finding the best method to hone in on certain genes, cells, or molecules associated with tumors could give physicians more flexibility in identifying the drugs that will deliver the best therapy for their patients.

Clinical investigators have incorporated these markers into the later stages of clinical trials to assist in reducing sample size and refining the patient population to get a better sense of the drug’s efficacy.

However, the traditional clinical trial design does not accommodate the biomarker-oriented approach within the earlier stages of the experiment.

Scott Marshall, Ph.D., Managing Director, Translational Informatics & Diagnostics at Precision for Medicine believes there are opportunities to incorporate these metrics into early-phase trials. His company is the, “first precision medicine research organization,” where they focus on biomarker driven clinical research to support life science companies.

Marshall’s background in biostatistics and formal training in statistical genetics and genomics has driven his career in translational research. He has analyzed the integration of biomarker data in clinical study contexts where the goal is often to answer questions related to drug development, such as how to characterize the mechanism of action associated with certain therapeutics for purposes of drug target identification and stratifying patient populations.

Marshall shared his insights with Drug Discovery & Development regarding the benefit these biomarkers could yield in early-stage trials.

DD&D: What are some types of biomarkers that could be beneficial in the early stages of clinical trials?

Marshall: A variety of biomarkers could be considered in the early stages of clinical trials and in large part the type of biomarker may be driven by the scientific objective. For example, is a biomarker being used to support dosing or to drive patient selection strategies and clinical trial design? Investigators could use biomarkers like immunohistochemistry (IHC) or genetic mutations to stratify patients to support various biomarker-guided adaptive designs and development of companion diagnostics.

However, to me, the key is to look at a variety of types of biological variation, and evaluate it all in the context of the clinical outcomes. We have been amazed at the new “multi-omic” signatures that we have uncovered. This approach of biomarker data management and informatics is where we see the true promise of biomarkers on display.

DD&D: Is there a specific disease research area where investigators could harness this approach?

Marshall: Where we have seen the most success has been in the oncology space where there is a much better understanding of the biology of the disease and what type of biological variation is underlying treatment response, non-response and acquired resistance. However, it is hard to imagine any trial without a biomarker approach, say, five years from now. The cost of therapeutic development is so significant, biomarker driven approaches is a clear way to reduce cost and timelines from discovery to approval to reimbursement.

DD&D: Do you see challenges or opportunities in other areas where a focus on biomarkers could work with trial design?

Marshall: An area such as central nervous system disorders presents challenges due to the heterogeneity of the diseases; however, we are seeing progress being made in terms of developing targeted therapeutics. And it seems like there may be opportunities within the autoimmune disease space or immunological conditions, as well as in rare and orphan diseases.

DD&D: What type of study designs could benefit from incorporating diagnosis based on biomarkers?

Marshall: There are various biomarker-guided (adaptive) study designs, leveraging both Bayesian and Frequentist methodologies. However, one particular design gaining significant traction and proving to be successful is the basket study type design. This is especially useful when exploring rare mutations and for selecting patients independent of tumor histology.

DD&D: What are the overall benefits of incorporating biomarkers into the first phase of clinical development?

Marshall: Incorporating biomarkers into earlier phases of clinical development can serve multiple purposes, ranging from helping to guide dose selection, to characterization of mechanism of action, to providing a strategy to inform patient stratification or selection. Additionally, the traditional stepwise march from Phase I to Phase II to Phase III has dramatically changed. Today, we see basket studies and adaptive designs, starting in Phase I with protocols that are amended to evolve directly into a pivotal study. So, this idea of early phase clinical development is changing. Biomarkers are the driver of these changes, and are significantly lowering the time and costs of clinical development. Ultimately, our goal is to support the development of safe and effective therapies for patients in a more streamlined and efficient manner. Biomarkers can help us do this, and I am excited to work with a passionate team every day to help make this happen.

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