|
|
 |
|
Viewing report
|
|
|
|
Post-Genomic Biomarkers: Revolutionizing Drug Development and Diagnostics 2nd Edition
Drug and Market Development Publishing, March 2005, Pages: 211
The first edition of this report, covering post-genomic biomarkers, was published in September 2003. Since that time, pharmaceutical and biotechnology companies have broadened from a primary focus on biomarker discovery to greater emphasis on assay development and implementation of biomarker applications. Since publication of the first edition, drug developers have also demonstrated increased interest in imaging-based biomarkers. This report, Post-Genomics Biomarkers: From Discovery to Implementation covers these and other new developments with the following specific objectives:
-To examine the impacts of Genome Era 'omic' technologies on the discovery and utilization of biomarkers
-To analyze the current and future impacts of post-genomic biomarkers on the pharmaceutical and diagnostics industries
- To assess the performance and viability of the industry segments that provide products and services for biomarker discovery/detection or offer biomarkers for license
-To examine the extent to which post-genomic biomarkers actually improve pharmaceutical R&D and clinical diagnostics
TECHNOLOGY BACKGROUND
A pragmatic definition offered subsequently by a pharmacologist working in the pharmaceutical industry suggests:'[A] biomarker is a measurable property that reflects the mechanism of action of the molecule based on its pharmacology, pathophysiology of the disease, or an interaction between the two. A biomarker may or may not correlate perfectly with clinical efficacy/toxicity, but could be used for internal decision-making within a pharmaceutical company.2'
These definitions have since been expanded to categorize biomarkers by degree of validity as exploratory, probable valid, and known valid. This and other categorization schemes can be used to determine how and where along the drug pipeline a particular biomarker might be useful.
THE INDUSTRY ENVIRONMENT
The pharmaceutical industry finds itself beset with multiple problems ranging from an oft-described and analyzed innovation deficit to continual, troublesome product withdrawals when idiosyncratic adverse drug reactions emerge. Causative factors include the complexity of current versus past disease targets, corporate growth requirements consequent to industry consolidation, and the related drive to focus on blockbuster drugs.
Efforts to increase industry productivity have focused on adopting new technologies (particularly the omic variety) and associated research strategies as a means to discover and validate new, improved drug targets and to advantageously exploit them.
TECHNOLOGIES
The recent explosion in biomarker activity has been fueled largely by the advent of omic technologies, which offer the ability to examine changes in a great many molecules at once in single experiments involving perturbation of biological systems. Drug researchers have generated mountains of such data and mined them to discover a host of new biomarker candidates, potentially useful in both pharmaceutical R&D and diagnostic applications. This scenario contrasts with those from a pre-genomic era in which biomarker discovery was so difficult that adoption of a new marker was a relatively rare event.
DNA microarrays, first popularized starting in the mid-1990s, drove a major paradigm shift in biological research driven by ready access to differential gene expression studies involving up to tens of thousands of genes. DNA arrays come in several varieties. These include two-dimensional, positional microarray and 'virtual' encoded bead varieties. Positional arrays are
further divided into spotted and synthesized varieties. Applied Biosystems and Amersham, for example, provide spotted arrays, while industry leader Affymetrix and runner-up Agilent offer synthesized units. Cross-platform agreement remains a difficult and critical issue for microarray manufacturers.
PRODUCTS AND APPLICATIONS
Although biomarkers are useful across all stages of the drug discovery and development process, they are currently used more often in research and preclinical development than in human clinical studies, where the need for extensive validation and assay optimization add stringency to the biomarker qualification process. Biomarkers of all types are proving particularly useful in early attrition of unpromising drug candidates, which supports pharma's emerging paradigm for improving R&D productivity.
In an example of biomarker utility for early discovery, Abbott Laboratories found that the BCL-2 gene expression could serve as biomarker to identify tumor cells sensitive to their drug candidate, ABT-737. Another gene, MCL-1, was identified as a marker of tumor resistance to this drug. These findings suggest a method for patient stratification in clinical trials. Biomarkers are particularly useful for preclinical studies in which they can serve to 'bridge' animal and human studies of both safety and efficacy. Biomarkers that define a drug's mechanism of action in vitro can be used to verify that the same mechanism operates in both animals and humans. Arguably, the most potent role for biomarkers lies in toxicity prediction. However, researchers have faced considerable difficulty in extracting nuggets of useful information from mounds of less relevant and often confounding data. Transcriptomic results from Iconix suggest the feasibility of predicting hepatoxicity using a 35-gene signature. The results, while less than perfect, demonstrate the potential of omic technologies for toxicity prediction.
Although the FDA is actively encouraging greater use of post-genomic biomarkers in clinical studies, pharma is moving forward cautiously in light of stringent validation requirements and the possible dangers inherent in providing more information than may be needed to demonstrate safety and efficacy. These risks increase in moving from early- to late-stage trials, so that post-genomic biomarkers are currently used less often in Phase III studies than in early stages.Post-genomic biomarkers are finding increased application in clinical diagnostics, driven by visions for personalized medicine and theranostics. Their promise is particularly strong for cancer diagnostics. The heterogeneity of malignant tumors often calls for multi-component biomarkers, a particularly strong suit for omic technologies. Conversion of biomarker discoveries to clinical analytes has been considerably hindered by the high costs involved in clinical validation, which are best borne by large diagnostics companies rather than less risk-aversive startups. The large diagnostics companies, unfortunately, are necessarily conservative in adopting early-stage programs. While pharma, diagnostics, and start-up companies actively explore possible business models, a modest number of post-genomic diagnostic programs are moving forward, primarily in large reference laboratory settings. At least 16 companies, mainly start-ups, are visibly active in the field.A number of companies, both large and small, are currently active in providing omic technology platforms for biomarker discovery and detection. A few venture capital–backed small companies are attempting, with limited success, to prosper via a business model featuring provision of biomarker services to pharma and biotechnology.
MARKET ANALYSIS
An analysis of the potential impacts of post-genomic biomarkers on pharmaceutical R&D expenditures generates a scenario featuring 14% savings by 2009. A survey of scientists engaged in biomarker discovery or validation/assay development revealed that the discovery component activity remains dominant, and that budgetary changes for 2005 versus 2004 range from reductions through stasis to significant increases, with the latter predominating. Regarding biomarker discovery, the survey reveals that DNA microarray usage is distributed among suppliers roughly according to market share. However, a surprisingly large proportion of users still opt to generate their own arrays. Regarding mass spectrometry instrumentation, users indicated a strong preference for Applied Biosystems units. In metabolomics, mass spectrometry proved the dominant modality, and for imaging, PET proved dominant followed by MRI. In considering pharmaceutical applications, early-stage activities dominated over later ones. For assay development, the Luminex bead platform and microarrays proved prevailed over alternatives.
FUTURE TRENDS
The future prospects for post-genomic biomarkers in pharmaceutical applications depend on the ultimate degree to which genomics succeeds in driving innovation. Using omic technologies and perspectives to drive reductionist drug discovery strategies may have inherent limitations. On an optimistic note, omic technologies adapt well to a more wholeistic systems biology approach to drug discovery, an area in which post-genomic biomarkers promise to play a central role.
Product samples
A sample for this product is available. Please Login/Register to download this sample.
Customers who bought this item also bought
Biomarker Technology Platforms for Cancer Diagnoses and Therapies
Biomarkers 2008
It's All About the Biomarkers: How 2008's Biomarker-Based Partnering Is Driving Personalized Medicine
Companion Biomarkers in Drug Development
Clinical Proteomics: Rethinking Approaches to Protein Biomarker Discovery
Cancer, CNS & Cardiovascular Biomarkers: Players, Products and Prospects
Biomarkers - Advanced Technologies and Global Market (2009-2014)
Advances in Biomarkers
Licensing Strategies for Accessing Biomarker Technologies
Biomarkers: The Future of Next-Generation Drug R&D
Biomarkers - Technologies, Markets and Companies
How Overcoming the Challenge of Biomarker Validation Can Pay Off for Drug and Diagnostic Developers
|
|
|
|
