A View from Inside the Studies that Drive Personalized Medicine

Leading up to the 12th Annual Personalized Medicine Conference this November, Slone Partners unveils a series of interviews with four key industry thought leaders.

This exclusive PMC series will gather unique perspective on innovation in personalized medicine, clinical outcomes, and reimbursement decisions with a special focus on solutions.

To set the stage, our first interviewee, Dr. Stephen L. Eck, discusses what he describes as life’s persistent questions as it pertains to diagnostics, drug development, and progress in the precision medicine space.

Slone Partners: In a recent blog article, you discuss the importance of transitioning from phenotype-based to genotype-based indications. For this to become a reality, multiple stakeholders (drug developers, diagnostics companies, psychiatrists, and physicians) need to be in lock step. Where do you begin to get to your ideal end-result?

Dr. Eck: We have historically described patients and their diseases based on what we could see. Initially this was by physical examination, but with every generation of new technology (microscopy, radiology, blood cell counts, chemistries) we refined our approach and in doing so differentiated similar but distinctly different diseases from each other. Molecular biology and genetics has taken this to a new level of detail wherein diseases that were once treated the same way are now treated quite differently (non-small cell lung cancer being the prime example). The ideal would be a molecular definition of all diseases, and in many cases this will be a genotypic description. This will resolve the current conundrum wherein diseases with the same phenotype may have distinctly different root causes and preferred therapies, and disease with the same genotype (but different clinical appearance) may benefit from the same therapy.

Slone Partners: What is our biggest obstacle to achieving that synchronicity over the next 2-3 years?

Dr. Eck: The rate limiting step is research on the biologic basis of disease. This will define why we have a disease and provide new opportunities for prevention and treatment. For pharmaceutical companies, having the optimal drug target is the holy grail of drug discovery and development. Cystic fibrosis is a great example of where knowledge of the precise genotype has led to impressive new genotype based therapies. Imagine if we could do the same for schizophrenia where our current therapies are largely tied to empiric observations made decades ago and are not yet based on the biologic basis of the disease.

Slone Partners: If you had a large fund dedicated exclusively to fixing one problem in the personalized medicine continuum, where would you invest that money and why?

Dr. Eck: Diagnostics! We need to give drugs to only those who will achieve the benefit intended. We should be approaching an era where absent the diagnostic test, the prescription won’t be written. Removing empiricisms from prescribing will improve outcomes and reduce overall costs. Unfortunately, we undervalue the role of diagnostics and this slows investment in answering the most fundamental questions: What disease do I have and what is the best therapy for me?

Slone Partners: How is personalized medicine affecting drug development?

Dr. Eck: Drug development has benefited from personalized medicine where it has been able to be implemented from the beginning of the R&D process. It shortens timelines and decreases costs. With the right patient population (defined by a molecular diagnostic test) the benefit (or lack of benefit) of a drug is readily apparent. Unfortunately we are still working on new medicines for diseases that are not well defined at the molecular level. This has led to efforts to retrospectively molecularly define the responding patients in the larger treatment pool. This is inherently more difficult, less efficient and requires later prospective validation.

Slone Partners: If you are starting a healthcare company that has to fit into the personalized medicine continuum, what do you think is the most overlooked area of focus and why?

Dr. Eck: Major affective disorders are an underserved area that would tremendously benefit from personalized therapy. These affect young adults and lead to lifelong disabilities and diminished quality of life (schizophrenia, depression, etc.). These disorders have strong genetic predispositions suggesting that getting at their root causes should be feasible with sequencing technology. Thinking that schizophrenia is one disease is equivalent to thinking cancer is a single entity, yet for now the choice of drug therapy for most psychiatric conditions is not based on understanding the molecular distinctions between individuals.

Slone Partners: How do we overcome the increased cost and complexity of advanced diagnostic testing in these early stages of personalized medicine?

Dr. Eck: We won’t decrease cost in the short run. New technology is often expensive when first introduced but cost declines with use. My first Hewlett Packard shirt pocket calculator cost $400 in the early 1970’s (a small fortune for a college student) and it replaced a slide rule which was essentially free. Now the calculator is free and can be found on every electronic device I own. The complexity will come down as we merge tests onto common diagnostic platforms and where multiplexing can be used to streamline testing. Add to this sample-to-answer technologies and the diagnostic testing becomes easy to use. This already exists for many infectious diseases where a small sample (stool, blood, respiratory secretions, etc.) is placed in a cartridge and the pathogen is identified within hours. These automated systems decrease the costs of technicians and provides near immediate information that the physician needs to decide on therapy

Slone Partners: Is there a tipping point at which we will see drug development streamlined as a result of more efficiency in diagnostics and clinical trials?

Dr. Eck: Yes and no. Currently, searching for the few patients that meet the diagnostic criteria for a study is time consuming and expensive (e.g., a high screen failure rates). As diagnostics better identify the patients who will benefit from a new therapy, we will need to find better ways to enroll patients who will be increasingly decentralized. In the ideal world every physician’s office, hospital and clinic could be a clinical trial site. The challenge is in making sure that we maintain the rigorous standards of data quality needed for drug approval studies.

Slone Partners: What areas of personalized medicine have seen the most rapid growth over the last 2-3 years? What do you project for the next 2-3 years?

Dr. Eck: Cancer therapies have been the largest beneficiaries of personalized medicine up until now. This has changed the business model of many pharmaceutical companies with an increased focused on diseases that have smaller and smaller patient populations. This can be adapted to other therapeutic areas as the molecular understanding of diseases increases. I think oncology will continue to dominate personalized medicine in the next 2-3 years, and we will see a dramatic rise in therapies for rare metabolic disorders (e.g., pyruvate kinase deficiency, propionic acidemia) as the biologic basis of these diseases are increasingly well understood (e.g., PCSK9 deficiency).

About Stephen Eck

Stephen L. Eck, M.D. Ph.D., joined Astellas Pharma Global Development in 2011 as Vice President, Oncology Medical Sciences. He is responsible for the design and conduct of domestic and international oncology clinical studies, which include the use of molecular testing for disease diagnosis and to monitor drug efficacy, and safety. Dr. Eck previously served as Vice President, Translational Medicine & Pharmacogenomics at Eli Lilly (2007-2011) where he was responsible for the clinical pharmacology components of drug development including both early phase clinical studies and late stage drug development studies. He was responsible for the Diagnostic and Experimental Medicines and Laboratory for Experimental Medicine departments which designed, built, and deployed novel clinical test platforms to be used in clinical studies. Dr. Eck previously led drug development teams at Pfizer (2002-2007), including the Molecular Profiling Group and the Translational Medicine organization.

Prior to joining the pharmaceutical industry, Dr. Eck was a member of the faculty of the University of Pennsylvania School of Medicine (Hematology and Oncology). He is a Fellow of the American Association for the Advancement of Science (Pharmacology). He joined on the Board of Directors of Luminex Corporation in 2016. He also serves on the Board of Trustees of the Keck Graduate Institute (Claremont, CA), on the Board of Directors of the Central Pennsylvania Clinic (Strasburg, PA); a non-profit healthcare organization for children and adults with rare genetic diseases; and on the Board of Directors of the Personalized Medicine Coalition (Washington, DC), a non-profit education and advocacy organization.

Dr. Eck attended Kalamazoo College (Chemistry) and earned doctoral degrees from Harvard University (Chemistry) and the University of Mississippi (Medicine).

In Slone Partners’ newsletter, we interview thought leaders from top companies to provide expert advice to leaders in the diagnostics, clinical trials, contract research, healthcare information technology, life science tools, and laboratory testing industries. Subscribe on our Newsletters page.