Biomarker diagnostics identify whether or not a patient has a critical genomic and / or proteomic profile associated with a particular disease or disorder. For example, in a person with symptoms of rheumatoid arthritis, the presence of rheumatoid factor in blood serum1 can confirm the diagnosis. There are many molecular diagnostic tests based on biomarker activity, and more will emerge as diagnostic research and development proceeds.
A companion diagnostic performs a similar, but different, service. The purpose of a companion diagnostic is to aid physicians in their decision-making process when prescribing drugs. The goal is to increase positive drug response rates and minimize adverse reactions. Patients vary in their response to prescribed drugs based on their genomic and proteomic profile. Some patients do not respond at all to certain treatments, and for other drugs, the precise dose required to achieve a response may vary. The patient’s underlying genotype and / or proteomic profile can impact drug efficacy. In response, pharmaceutical researchers have applied DNA sequencing, assays, and screens to find biomarkers2 responsible for response variability. If one or more are located, pharmaceutical companies then design a diagnostic kit to test for its presence prior to drug administration. Companion diagnostic assays can be based on cellular function, or they may target specific molecules. In the latter case, they usually target specific DNA mutations, posttranslational protein expression, or structural variations at the molecular level.
Often, time to therapy will result in varying response to treatment. Ideally, any companion diagnostic is available at the bedside and can rapidly identify patients with a genomic or proteomic biomarker, or in some cases a set of markers, statistically associated either with reduced or improved drug response.
Until recently, most companion diagnostics have been mainly designed with drugs for which dose customization is important (coumarin-based anticoagulants)3 or for which failure to respond presents an important clinical problem (for example, interferon-α treatment in hepatitis C infection).4 Today, almost all pharmaceutical companies are designing clinical trials with biomarker components — collecting DNA samples and detailed data on response as part of the study. Researchers are designing even more clinical studies (Phase IIb/III) with a biomarker as inclusion for randomization with a requirement for an Investigational Device Exemption and pre-market approval.
The U.S. Food and Drug Administration recently recognized the importance of companion diagnostics and personalized medicine by introducing draft approval guidelines for targeted drugs only in the presence of matching companion biomarker diagnostics.5 For pharmaceutical companies, this presented a potentially significant challenge for their existing targeted therapies for which no companion diagnostic exists and, at the same time, opened up a new area for new research and new revenue.6 Globally, regulators are more frequently approving companion diagnostic tests alongside therapeutics. As a result, pharmaceutical companies include the tests within the drug label, creating a new revenue stream for themselves and enabling clinicians to further stratify and subgroup patients along the road to personalized medicine.
- Agarwal, A. (2012) ‘Do companion diagnostics make economic sense for drug developers?‘, New Biotechnology, published online May 1, 2012. doi: 10.1016/j.nbt.2012.04.004
- Daly, A. (2010) ‘Genome wide association studies in pharmacogenics‘, Nature, 11 (4), (pp. 241-246)
- Suarez-Kurtz, G. and Botton, MR. (2012) ‘Pharmacogenomics of Warfarin in Populations of African Descent.’ British Journal of Pharmacology, published online June 7, 2012. doi: 10.1111/j.1365-2125.2012.04354.x.
- U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (2011) ‘Draft Guidance for Industry and Food and Drug Administration Staff: In Vitro Companion Diagnostic Devices.’ http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM262327.pdf
- Westwood, O.M., Nelson, P.N., and Hay, F.C. (2006) ‘Rheumatoid factors: what’s new?‘, Rheumatology, 45 (4), (pp. 379-385)
- Zieba, A. et al. (2012) ‘Molecular Tools for Companion Diagnostics.‘ New Biotechnology, published online May 23, 2012. doi: 10.1016/j.nbt.2012.05.004