Metabolomics: Improving the Route from Early Drug Discovery through Clinical Development

Dec 18, 2017

Drug development is a risky and complex process; just 12% of drugs entering clinical trials ever make it to patients.And thousands of molecules never make it past discovery and preclinical testing. It is vital to have confidence that a target is relevant in human disease and that the molecules directed against a given target are potent, safe, and efficacious.

R&D decisions are frequently based on abstract information. While researchers have a wide range of tools available—from genomics to structural biology to rational drug design—the combination of these tools doesn’t always yield definitive insights. Some technologies, such as transcript profiling, provide an overwhelming amount of data that does not produce clear signals without substantial investment. On the other hand, measuring only a limited number of markers may exclude key insights. In many instances, accepted assays or biomarkers omit important pieces of information that can lead to blind spots in decision-making.

Researchers need data that provides a comprehensive, physiologically, meaningful assessment of a living system (cells, animal models and human) and links it to how a target/molecule combination or therapeutic affect that system. This type of data would enrich decision-making from discovery through the clinic and is precisely what metabolomics provides.

Metabolomics is the study of the metabolome, all the small molecules (metabolites or biochemicals) in a living system. Metabolomics technology enables comprehensive measurement and interpretation of the metabolome. As the products of biological networks, the microbiome or exposure (diet, drugs, etc.), metabolites serve as a proxy to the physiological changes accompanying disease and drug response. Importantly, these changes are agnostic to the target class, from traditional targets to new therapeutic approaches. This data makes metabolomics a key ally for driving decisions in pharmaceutical R&D that build program confidence and reduce attrition by aiding in the selection of high-quality targets, molecules and translatable biomarkers across all major therapeutic areas.

Metabolomics is integral to understanding target biology, the translational potential of models, and a molecule’s mechanism of action and its effects (pharmacodynamics, efficacy and safety). In addition, it is used in clinical development to evaluate and stratify patients for treatment and patient selection during recruitment, to monitor participants throughout a study, to assess the overall quality of the study, and to better understand drug effects.

The value of metabolomics is ultimately best realized when applied across program milestones. The technology (measuring all the small molecules) can be used to help design more precise preclinical models, pursue the right targets, and select the correct patient populations for faster, more cost-efficient clinical development. More importantly, insights and biomarker assets can be leveraged from discovery through the clinic to build infrastructure across programs. Comprehensive metabolomics technologies, however, are extremely rare. Deriving knowledge from the huge quantities of data produced can be a daunting and time-consuming task for most R&D labs. Metabolomics tools and technology partnerships can facilitate the successful application of metabolomics in pharmaceutical R&D.

Beyond the pharmaceutical R&D stage, metabolomics-based companion diagnostics may even help physicians prescribe the best pharmaceutical therapy based on the individual’s metabolic profile. Metabolites, such as glucose and cholesterol, are already clinical assessment staples used by healthcare providers, but there are thousands that can be measured to create a comprehensive snapshot of a patient’s health.

The biggest challenge, and one seen across precision medicine approaches, is how to provide actionable information to the physician from all the big data generated by multi-omics. We must do a better job translating the science for physicians; we must help them utilize that powerful data to optimize health care. This may involve making proper validations of the molecules to define the analytical parameters and extensive clinical validations in a well-defined target population for each of the specific disease target, as compared to a clinically normal reference cohort. Additionally, longitudinal study, intra-subject and inter-subject biochemical profiles will also be required for an accurate interpretation. Lastly, all this information will have to be presented in an easy-to-understand format to assist the physicians in patient management.

Metabolomics can make a positive impact from early drug discovery through clinical development and beyond. The technology not only provides data that drives better decisions in the pharmaceutical research and development world, but also has the potential to re-shape how medicine is practiced in the 21st century.


1Pharmaceutical Research and Manufacturers of America. Biopharmaceutical Research & Development: The Process Behind New Medicines. Available at: Accessed: 10-23-2017.


John Ryals, PhD, CEO, Metabolon, Inc.

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