Abstract

The Utility of Biomarkers in CNS Drug Development

Alan Palmer, CSO, M S Therapeutics Ltd

A biomarker can be defined as a biological variable that has a statistically significant relationship with parameters of disease states or the activity of a drug or drug candidate. Biomarkers are fast becoming an essential part of clinical development, largely because they: (i) offer the prospect of more homogenous patient populations in clinical trials through patient selection and stratification; (ii) permit assessment of target engagement; (iii) allow the consequences of target engagement to be measured; and (iv) provide markers of disease modification. Because biomarkers can increase the statistical power of clinical trials and predict drug efficacy more quickly than conventional clinical endpoints, they hold the potential to substantially accelerate product development and increase confidence of demonstrating therapeutic efficacy in Phase III trials. CNS drugs take 35% longer to complete clinical trials and gain regulatory approval compared to other new prescription medicines, so CNS is the therapeutic area that stands to benefit most from the effective application of biomarkers in the clinical development process. For most disorders, biomarker measurements derive from the determination of a biological variable in blood samples, but, because of the existence of the blood–CNS barrier, this is not true for CNS disorders. The blood–CNS barrier (BCNSB) comprises the blood–brain barrier, the blood–spinal cord barrier and the blood– CSF barrier. Together they separate the bloodstream and the CNS and, thus, largely undermine the use of blood biomarkers for CNS disorders. Examples of the utility of biomarkers in the development of CNS drug candidates will be described.