In vitro molecular diagnostics have established themselves as effective tools for all aspects of disease management, especially in areas of unmet clinical need. Such tests have been developed for screening and prognosis as well as for applications, such as determination of genetic predisposition to disease, detection of presymptomatic disease, and prediction of individual drug response. Molecular diagnostics are the basis of pharmacogenomics, enabling the evolution of personalized medicine.
In Drug and Market Development’s (D&MD) recently published market assessment report entitled “Molecular Diagnostics: Effective Tools for Disease Management”, molecular diagnostics is taken to include tests for small-molecule, protein, or nucleic acid biomarkers and is mainly concerned with biomarkers that are measured using marketed clinical laboratory test kits or clinical analyzers. Biomarker assays are increasingly used throughout the process of disease management. A well-developed example is the use of HIV tests, including probe-based nucleic acid tests (NATs) for viral genotyping, in the management of AIDS patients.
Molecular diagnostic tests typically analyze key DNA, RNA, or protein biomarkers (analytes) to identify a disease, determine its course, evaluate response to therapy, or predict individual predisposition to a disease. The techniques applied involve analysis of DNA sequences, DNA methylation patterns, gene expression profiles, proteins, protein expression, or combinations of these biomarkers. Such biomarkers provide direct information about genotypic and/or phenotypic changes associated with specific diseases or responses to treatment. Biomarker analysis has also become an important tool in drug discovery, preclinical drug development, and patient monitoring during clinical trials.
Regulatory events of note during the last two years include FDA approval of the first DNA microarray instrumentation system for in vitro diagnostic use (Affymetrix’ GeneChip System 3000Dx) and the first highly multiplexed diagnostic microarrays: Roche’s AmpliChip CYP450 test and two cystic fibrosis tests—Tm Bioscience’s Tag-It and Osmetech’s eSensor. Although not yet approved by the FDA, tests based on transcriptomic profiling have also debuted successfully on the market.
The first generation of marketed molecular diagnostics have been based on established immunoassays and NAT technologies. Although the NAT market continues to be dominated by Roche, Abbott Laboratories and Bayer, many biotechnology companies have recently acquired significant IP property in this area.
The company leaders in immunoassay and NAT identified in the D&MD Report include Roche Diagnostics, Abbott Laboratories, the Ortho Clinical Diagnostics and Lifescan units of Johnson & Johnson, Beckman Coulter, Bayer Diagnostics, Becton Dickinson, Dade Behring, and bioMerieux. Important niche suppliers include Agendia, Bio-Rad, Biosite Diagnostics, Cepheid, Chembio Diagnostic Systems, Chiron (Novartis), Ciphergen Biosystems, Correlogic Systems, Cytyc, DiagnoSwiss, Diagnostic Products, Digene, DiaSorin, Epigenomics, EXACT Sciences, Gen-Probe, Genaissance Pharmaceuticals, HandyLab, Innogenetics, Interleukin Genetics, Matritech, Myriad Genetics, Nanogen, Nuvelo, Nymox Pharmaceutical, OXIS International, Proteome Sciences, Sequenom, SomaLogic, Sysmex, and Third Wave Technologies.
Current molecular diagnostics are primarily single-analyte tests involving the detection of a single gene or protein. However, many disease-related processes are multifactorial, involving the abnormal expression of multiple genes or proteins. Second-generation molecular diagnostics are anticipated to utilize novel detection technologies and multiplexing platforms to allow the measurement of a large number of analytes simultaneously. These innovations will increasingly utilize multiplexing platforms such as DNA microarrays that perform parallel biomarker analyses.