Biomarker use in drug development

With Philippe Goix, Singulex

NGP. What biomarkers are being used to allow for drug development?
PG. Biomarkers, are widely used in virtually all therapeutic areas including; Cardiovascular (e.g. Cardiac Troponin I), CNS diseases (e.g. Amyloid βeta 40, 42), Oncology (e.g. VEGF, Akt-1, PSA), Metabolic Diseases (e.g. Insulin, GLP-1), and Inflammatory Diseases (cytokines and chemokines). Biomarkers serve a variety of different purposes in support of pharmaceutical development; a wide range of biomarkers are being used in drug development covering nearly all classifications of analytes, including proteins and metabolites, genetic markers, DNA, RNA and many others across a wide range of platforms. For example, Singulex immunoassays focus upon proteins such as cytokines, chemokines, growth factors, transcription factors, and hormones, regulatory proteins such as troponin and metabolites such as cAMP.

NGP. Why are biomarkers important for personalised healthcare?
PG. Biomarkers are used in personalised healthcare as a diagnostic tool to identify populations for stratification and abnormalities in individuals, to be better able to tell who can benefit from therapies and to track individual disease progression. They are also used  to modify or switch therapies when one mode is not successful, and also to maximize the utilisation of drugs e.g. to better enable drugs and delivery modes to be cost effective

NGP. How can they be used to measure disease progression?
PG. Many biomarkers can be used as progression monitors from normalcy. The primary logic is that there are baseline levels of biomarkers that can be measured in individual patients.  By following the patient over time, medical professionals would be able to monitor the progression from any given state, either healthy to sick or preferably sick to healthy. It is hoped that the detection of the disease arrives in time for a therapeutic intervention.

Many biomarkers that are clinically relevant, however, are difficult to monitor with given technologies currently available (such as lacking the necessary sensitivity to measure the changes). By increasing assay sensitivity, it is possible to observe the minute levels of the analyte of interest. Thus, allowing for observation of small incremental changes (approximately 50-250 fg/mL) from a given state providing the researcher or clinician with vital data about the efficacy of a given drug or treatment regimen.

For example, Singulex has pioneered development of a very sensitive troponin I assay.  With this assay it is possible to observe very small changes in troponin.  In placing patients on a treadmill it is possible to observe a difference between resting states and exercise states and determine those at highest risk. Our work with rats verified that many of the same principals apply to animals and troponin.

NGP. How can efficacy and safety be successfully balanced during drug discovery?
PG. By increasing sensitivity, the therapeutic index can be optimised on both ends (safety and efficacy) to obtain the optimal amount (least amount) of drug to have the greatest effect.  To accomplish this task requires a reproducible and sensitive surrogate biomarker.  Knowing the stability of the analyte in your population helps to provide a framework or a relevant base from which to measure. With this baseline of the biomarker/analyte one can observe significant changes beyond baseline variation.

Surrogate biomarkers can track disease severity and the effect of the drug to modify or minimise the disease. Additionally, there are specific markers that are indicative of toxic effects and can be monitored in relation to the efficacy of dosage.

Philippe J. Goix, Ph.D., is the President and CEO of Singulex, Inc. Dr. Goix took the position in 2004 to spearhead Singulex’s commercial efforts in the life science and diagnostic markets. Previously, he founded Guava Technologies and was a senior scientist at Sandia National Laboratories, Stanford University, and CNRS France.