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Can Pathway-Based Approaches Overcome the Problems of Target-Based Drug Discovery?
Decision Resources, Inc, June 2006
After the human genome was sequenced, pharmaceutical and biotechnology companies hoped that their enormous investment in drug discovery and development programs--$51.3 billion in 2005--would yield higher R&D productivity. However, the industry’s target-based research approach has failed to generate many drugs that work via novel mechanisms of action, and drugs that fail late in clinical trials significantly drive up the overall cost of drug development. Companies are now reevaluating their drug discovery research strategies, implementing or considering a shift to a pathway-based approach in the hopes of unlocking the promise of genomics-based drug discovery. By studying the routes by which drugs act on a system (i.e., a signaling pathway or network) rather than simply scrutinizing a specific target, companies hope to better understand how a disease progresses, which they hope will in turn lead to better-designed and more effective therapeutic strategies.
In this report, Decision Resources Inc discuss recent progress in pathway-based drug discovery. They review studies aimed at expanding researchers’ knowledge of key pathways and those that use whole-pathway screening methods. Decision Resources Inc also highlight the application of pathway-based methods to drug discovery and translational medicine and discuss the impact of pathway-based strategies on pharmaceutical R&D.
Business Implications
- In the post-genomic era, target-based drug discovery has been less productive than the pharmaceutical industry companies had hoped. In contrast, discovery based on the study of intracellular signaling pathways, mostly based on academic research, has been a successful post-genomic drug discovery strategy. This approach has yielded, for example, a proliferation of kinase inhibitors for cancer treatment.
- Drug companies are interested in expanding their knowledge of pathways to identify large numbers of proprietary, validated targets and in assessing the impact of drugs on pathways. These needs have fueled the development of novel pathway expansion and whole-pathway cellular assay technologies. Companies active in these areas include BioImage, Bionaut Pharmaceuticals, BioSeek, Cellzome, and Hybrigenics.
- Pharmaceutical companies are implementing new pathway-based technologies and strategies in their R&D programs. Novartis is leading the way in this arena and has restructured its entire R&D program around pathways. Although no other big pharma has so thoroughly reoriented its research strategy around pathways, interest in these approaches is spreading throughout the industry.
- Drug candidates arising from new pathway studies are still in the research and preclinical stages. Until companies obtain proof-of-concept of these drugs in human clinical trials, the success of the new pathway-based paradigms of drug discovery remains unknown. Nevertheless, Decision Resources Inc expects that new pathway-based technologies and strategies will penetrate the pharmaceutical industry in the next several years.
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