The Benefits of Personalized Medicine

Pharmaceutical Technology spoke with Jonathan Sheldon, PhD, global vice-president, Oracle Health Sciences, about how industry can benefit from personalized medicine.

PharmTech: How can the pharmaceutical industry benefit from personalized medicine?

Sheldon: From the recent activities and re-focus of R&D efforts within the pharmaceutical industry, there is an active effort to develop new drugs with some sort of ‘biological’ component (i.e., some sort of a ‘biomarker’ or surrogate marker) that could be indicative or a predictor of a beneficial efficacious effect and/or a reduction/elimination of an untoward adverse effect.  With shifts in the healthcare environment toward targeted/personalized treatments to improve patient care and achieve better outcomes, all while taking money out of the healthcare system, it is apparent that the old paradigm of drug development is no longer sustainable.  With this overall healthcare trend, development programs have moved beyond demonstration of safety and efficacy to include more data on clinical utility as well as comparative effectiveness.  Therefore, development programs have evolved from enrolling ‘qualified’ patients to enrolling ‘well-characterized’ patients, using ‘omics’ and other potential surrogate clinical markers/criteria, as criteria for potential patient inclusion.  With the inclusion of well-characterized patients with the targeted ‘omics’ marker(s), it is hoped that through the use of an enriched patient population, studies can be smaller, generate better data and, hopefully, be done more quickly.  The main issue to address, however, is incidence and prevalence of the ‘omics’ marker in the population intended for treatment.  If the ‘omics’ marker is present in 10% of the patients, it may still require a large number of sites to find and enroll those patients, albeit the overall probability of study success would be substantially higher, if the hypothesis that those with the specific ‘omics’ marker do, in fact, demonstrate a beneficial effect of the drug. 

Through the use of this type of patient inclusion approach as early as possible in the development program, it is hoped that adequate data can be collected to make the critical end Phase II a go/no-go decision quicker.  With the ability to make these critical decisions earlier, it is possible to dedicate limited R&D resources toward the development of candidates that have the best chance of clinical, regulatory, and commercial success to bring targeted medical treatments to the market as soon as possible, for the benefit of all engaged in the healthcare continuum.

PharmTech: What kind of data can be gathered and used by the pharmaceutical industry for drug development in personalized medicine?

Sheldon: Data from multiple sources are available to pharma companies to help in their development programs, including payer claims data.  With the evolution of electronic medical records (EMR) systems, the potential to gain more direct patient care data is also creating avenues for expanding the ‘big data’ sources available to pharma.  In addition, there are companies that provide large data aggregator services covering many topics, including ‘omics.’  These groups often abstract key data elements out of global published literature to offer aggregate and detailed data on validated genetic variants as well as those that may be suspected of being related to a given disease indication.  The main challenge that many pharma companies face, however, is the ability to aggregate all of the data from multiple sources into a single, standardized, and normalized database, or data warehouse, to be able to apply high-level analytics and effectively use these large and disparate data sources.  With the advent of sophisticated data collection technology, the volume of available data is drastically increasing.  As such, the challenge is storing, integrating, analyzing, interpreting, and using this data for the greatest benefit.

PharmTech: What are the challenges that pharmaceutical companies face in developing personalized drugs?

Sheldon: The depth, breadth, and volume of data from multiple disparate sources can be overwhelming.  Being able to compile large volumes of the most useful data is a tremendous challenge in its own right.  However, being able to collect, store, integrate, analyze, and interpret these data can prove to be the biggest challenge.  With data being collected and/or derived from various sources, being able to store data in a common, standardized, and normalized manner to be able to use it effectively is one of the greatest challenges facing pharmaceutical companies.  Once the data are available in a standardized and normalized data structure, it can be used for tremendous benefit.  In the personalized medicine space, use of ‘omics’ markers creates multiple challenges.  In oncology, the use of biomarkers is well accepted and defined, but continues to develop and evolve as new genetic variants are defined and validated.  Other therapeutic areas are not as well defined, so the challenge there is to fully appreciate both the genotypic and phenotypic expression of potentially numerous genes/gene variants in various indications, such as schizophrenia, diabetes, and Alzheimer’s Disease, where there may be multiple ‘omics’ markers associated with an indication.  So, knowing which ones are the most important and/or best targets for intervention that actually do have an impact on the manifestation of the disease itself, is a tremendous challenge. 

Likewise, understanding the incidence and prevalence of any potential use of an ‘omics’ marker in a target population can be another daunting challenge.  The cost-benefit analysis of being able to develop new therapies for indications where a smaller percentage of patients could benefit versus the entire available patient population is also a critical challenge.  The analysis can be even more complicated when the interests of the multiple stakeholders (patients, payers, and providers) are considered.

Overall, the convergence of the therapeutic development process, from the bench to the bedside to the payer, creates new and broad challenges to pharmas, as well as the stakeholders across the entire healthcare continuum.  However, the evolution of the healthcare environment globally will continue, and we all have to adapt to ensure our collective and mutual success.