From The Editor | June 4, 2015

Marking The Present And Promise of Biomarkers

By Louis Garguilo, Chief Editor, Outsourced Pharma

Louis Garguilo

Years ago a business development manager attended a New York Biotechnology Association (NYBA) annual meeting to see if he could drum up work for his CRO. Upon return to the office, his CEO asked what he found. “I’m not sure what they are,” said the BD manager, “but we better get in the business of providing biomarkers! Everyone was talking about them.”

Those BD types … but more importantly, those biomarkers. They are becoming an industry unto themselves: they have their own FDA tables and World Congress, and have been before the Supreme Court (Mayo v. Prometheus). Biomarkers also provide outsourcing companies with growing business opportunities.

At the same time, it’s always good practice to temper enthusiasm with a reality-check on the real-world status of the development and application of any science. For help in this assessment, I reached out to a professional at a CRO taking full advantage of the biomarkers field. Rabia Hidi is managing director, Biomarkers and Biopharmaceutical Testing Unit, SGS Life Science Services. She’s a ten-year veteran of Pfizer, and has devoted her career to this field. Here’s what she says about the current state of biomarker science, and its future potential:

“There’s an increasing need for the integration of biomarkers in development and clinical practice to improve the selection of drug candidates, increase the speed of the entire development process, and bring better drugs to market.

"To be clear, though, while much progress has been made, and biomarkers have been accepted by FDA for specific applications, there are still many questions that need to be answered. An example is the use of pre-clinical biomarkers for prediction of toxicity and safety in clinical use. Even more challenging are rare diseases, where the use of biomarkers is still at an early stage of research.”

Today, a growing cadre of scientists work as clinicians, bioanalysts, statisticians, and assay platform providers to support the development and validation of biomarkers. The NIH formed a pubic-private consortium to “discover, develop, and seek regulatory approval for biological markers (biomarkers) to support new drug development, preventive medicine, and medical diagnostics.” Research is ongoing to evaluate, validate and qualify biomarkers for therapeutic areas such as oncology, cardiovascular diseases, obesity, depression, diabetes, sepsis, rheumatoid arthritis and Alzheimer’s disease.

Much work done; much left to do. And while biomarkers are at the beginning of their potential to impact science and patients, consider that in 2014, more than 20 percent of the novel new drugs approved by FDA’s Center for Drug Evaluation and Research (CDER) are considered “precision medicines,” the new banner under which biomarkers fall.

“I see us at two fronts,” says Hidi. “First, work is moving forward with the help of new platforms offering high throughput for the discovery of new molecules. Then there are the known molecules whose clinical validation and qualification is not yet confirmed. Both require we identify biomarkers and their relevance to the mechanism, then validate them to be sensitive and specific enough for use during drug development and in clinical practice.”

A Wide Mark On Drug Development

Biomarkers are one of those scientific advances that the public grasps quickly, as easy to understand as the PSA number men receive during their annual health checkup. As mentioned above, they are also a component of the exegesis of “precision medicine,” and are made manifest by progress in pharmacogenomics.

Borrowing directly from the Coriell Institute, biomarkers can be any measurable characteristics of an organism that reflect a particular physiological state. They are often compounds isolated from body fluids to assess the effectiveness of drugs and therapies. Biomarkers are important in the development of new drug therapies through the discovery of "druggable targets." They can include proteins or peptides; antibodies; cell types; metabolites; lipids; hormones; enzyme levels; physiological states; imaging studies of organs, or substances introduced into patients to assess functioning organ systems.

All these avenues of research and application, and the growing demand for inclusion in regulatory submissions, makes it clear that the CRO industry will see more demand to do biomarker work.

A Platform Not Too High For Market Entry

A simple web-search verifies the demand; it turns up hundreds of organizations offering biomarker-related services for academic, bio- and pharma-based drug-researchers. Unlike other areas Outsourced Pharma has covered recently – aseptic services comes to mind – there appears to be a lower barrier to market entry for biomarker services. “The field is competitive with established players, and theoretically at least, it’s possible to quickly start up operations in small labs,” explains Hidi.

She adds that sponsors have undertaken different strategies for outsourcing their biomarker research. Some Pharma, for example, handle all exploratory and discovery work internally, while others outsource biomarker activities from early stages through application in clinical trials or diagnostic testing.

At the early stage, biomarkers can be tested in samples from biobanks or collected in academic institutions, often via collaborations. These samples are valuable for screening of candidate biomarkers, using bioanalytical platforms with the required throughput and sensitivity.

Once the most promising biomarkers are selected, they are qualified in clinical studies (e.g., in phase 1 studies or in dedicated biomarker methodology studies) to check reproducibility, the best design for sample collection, suitability of the bioanalytical method, etc. The level of method validation becomes more important as the process moves on. Activities associated with biomarker development and qualification includes statistical analysis of biomarker data, modeling and simulation, logistics for sampling, storing and shipping samples.

No matter the strategy or service, Hidi recommends that sponsors take a conservative approach and outsource to proven entities using confirmed platforms. SGS has reinforced its own platform strategy recently, adding a new capability for biomarker testing, by further investing in the Roche COBAS system 6000, first introduced at the SGS facility in Poitiers, France, in June 2014. The system was already equipped with a clinical chemistry module for small molecule and analyte testing. The expansion adds an immunoassay module used for the quantification of large numbers of cytokines, hormones, and other biomarkers for disease areas such as oncology, endocrinology, sepsis, anemia and cardiac disease. The module further supports risk assessment, safety, and efficacy testing in the development of biomarkers.

“It seems day-after-day we see emerging platforms,” comments Hidi, “but we follow a cautious approach, investing only in platforms with proven bioanalytical maturity. That means already gaining acceptance from the FDA, and the scientific community, through ample data published on the platform. Examples are the Luminex, ECL-based MSD platform, and other automated systems.”

According to Hidi, it’s also important to maintain platform consistency to allow meta-comparison of biomarker data between studies. This adds overall to developing confidence throughout the industry in the use of candidate biomarkers. “At the least,” she says, “for biomarkers to be used for decision-making, as a pharmacodynamic end-point or for safety testing, new platforms should be used cautiously.”

With biomarkers, then, like other recent advancements in the creating and administering of medicines, much promise has been realized while further progress will be attained through steady research and a conservative approach. And service providers should continue to play an expanding role in the proliferation of biomarkers.