L3.1 The Challenges of Drug-Diagnostic (RX-DX) Co-Development: A Biopharmaceutical Perspective

Abstract

ABSTRACT There has been a major shift from conventional tumor histology alone to a biologically defined stratified approach that has led to the development of new cancer therapies and improved outcomes for cancer patients. The increasing technological power to interrogate the genome and other biologic processes, combined with sophisticated informatics, will continue to provide new biomarkers for targeted cancer therapies. While these factors are accelerating targeted cancer therapy, there are a large number of practical issues that need to be considered in the context of biopharmaceutical development and the marketing of new therapies that require a companion Dx. A Rx-Dx companion “product “should provide for appropriate therapy decision-making in the context of medical need. The strength of evidence for this typically comes from prospective clinical validation studies. Assay performance that meets technical analytical and classification accuracy criteria (including cut-off determination to define biomarker positive vs. negative) is critical for the prediction strength of the biomarker-endpoint relationship. Value creation is another important consideration for BioPharmaceutical and Diagnostic companies. This can be measured in terms of Rx or Dx development productivity, return on investment, and costs/benefits to the health care system. A Dx product intended to identify patients for a specific Rx therapy is a complex system of procedures, reagents, instruments, software, and algorithms, all of which may comprise the regulated product. A typical Dx development process includes discovery and feasibility research, product development, product verification and validation and regulatory approvals and commercialization. There are different regulatory expectations for Dx products across the world. The BioPharmaceutical company needs to integrate the Dx development and regulatory requirements with that of the Rx development and regulatory requirements. The recent approvals of vemurafenib with its companion cobas V600 mutation test and of crizotinib with its companion ALK FISH DNA probe assay are examples of how this can be achieved. Recognizing and managing the practical considerations, challenges and time required are critical to enabling successful Rx-Dx companion development to achieve the mission of delivering targeted health care to cancer patients.