Personalized Medicine, What’s the Future?

Personalized medicine is currently one of the hottest areas in life sciences, imparting significant levels of excitement among venture capitalists, life science companies, clinicians and patients.  It even has its own journal that “translates recent genomic, genetic and proteomic advances into the clinical context.” As Snowfish has had the privilege of working with genomics companies, we have heard firsthand the potential impact these new technologies will have on the way patients are treated and how the industry does business. 

In brief, personalized medicine refers to the customizing of medical treatment to the individual characteristics of each patient. Contrary to a common perception, it does not refer to the creation of drugs or medical devices that are unique to a patient but rather, the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment. This information ensures that interventions are targeted only to those who will benefit, thus sparing expense and side effects for those who will not.

Most medical professionals will concur with the fact that patient response to both disease and therapeutic intervention are highly variable.  It is not uncommon for one patient to respond beautifully and tolerate a drug without incident and another to experience side effects while obtaining no benefit.  Depending on the source it has been documented that 30% to 70% of patients fail to respond to a drug treatment.  There is a variety of potential reasons including adherence, and even misdiagnosis.  Still, it seems highly probable that patient-specific factors such as variability in drug metabolism rates, the metabolic or genetic nature of the underlying disease, and other characteristics such as age are also contributing factors.  Enter personalized medicine.

Oncology is where personalized medicine appears to making the greatest amount of headway.  This makes sense as treatment response rates in cancer are amongst the lowest for any major disease.  The well-established genomic basis of cancer has put cancer research at the forefront of personalized medicine in the quest for more targeted and tolerable therapies.  Early examples of success are Herceptin in breast cancer and Gleevec in chronic myeloid leukemia (CML).

Various technologies are being employed in the effort to more effectively guide the treatment strategy based on the likelihood that the cancer will recur or metastasize.  For example, the clear molecular differences seen in breast cancer are highly applicable to genomic profiling, and through transcriptional profiling approaches, several prognostic and predictive assays have been developed. Prominent amongst these is Genetic Health’s Oncotype Dx, a 21 gene polymerase chain reaction (PCR) panel that predicts tumor recurrence at ten years in estrogen-receptor (ER)-positive, node-negative breast cancer patients receiving tamoxifen therapy. [1] Using a statistically defined algorithm, the gene expression profile is used to define a recurrence score that can be used to identify patients who are likely to benefit from additional adjuvant therapy. Patients with low recurrence scores and, therefore, good prognosis are spared the stress and risk of unnecessary therapy, and the healthcare system saves the costs of delivering additional treatment.  The assay has been endorsed by both the Association of Clinical Oncologists (ASCO) and the National Comprehensive Cancer Network.

Although it is one of the first, and certainly the one of the most successful to date, it is already clear that Oncotype Dx is merely the tip of the iceberg. In breast cancer alone, we have seen the emergence of multi-analyte tests based on techniques as broad as PCR, microarray, immunohistochemistry and fluorescent in situ hybridization, amongst others.   Genomic Health is also expanding the use of their assay in breast cancer as well as developing similar prognostic test for colon cancer, prostate cancer, non-small cell lung cancer, melanoma, and renal cancer. 

One of the main obstacles to the growth of personalized medicine has been cost.  Until very recently the devices used for genome sequencing cost $500,000 to $750,000.  Additionally, the individual tests run $5,000 to $10,000 and take days to produce results.  Things are changing though.  Just this past year, Life Technologies introduced an Ion Proton™ Sequencer that is designed to sequence the entire human genome in a day for $1,000 and the machine costs $149,000.  Clearly, the barriers to affordability are breaking down.   It is not hard to imagine that the cost of a complete genomic testing will be a few hundred dollars within a few years. [2]

In order to realize the full potential of personalized medicine, engagement of multiple stakeholders is critical.  Payers will need to be convinced of the clear benefits of specific genetic tests.  As companion diagnostics are critical to development and utilization of therapies, the Federal Drug Administration (FDA) will need to promulgate clear and straightforward paths for diagnostic approvals.  Clinicians will need to modify existing treatment regimens and include genetic testing as a core component and feel confident to withhold standard therapies when genetic testing indicates that these treatments are ineffective or no more effective than watchful waiting.  Treatment guidelines will require modification in order to account for the genetic makeup of patient populations.  Life science companies will have to develop a new mindset; where the goal is not the single multi-billion dollar blockbuster but rather a portfolio of more products which treat smaller populations.  That said there could even be the potential to review the “shelves” of failed products to determine if there could be success with a more appropriate genotype or phenotype.   

Personalized medicine is upon us and it will completely revolutionize how treatment is determined. Today, clinicians choose therapies based on research done on thousands of people that have a diverse genetic profile and have only a limited ability to adjust therapy based on individual differences.  In the case of cancer, treatment is currently based upon the tumor location.

In the future, the tumor itself will be tested and it will be based less on the location than on its genetic and molecular composition. Genomic testing will be able to identify which oncogenes are turned on and which oncogenes are turned off.   Most importantly, clinicians will be better able to identify the drugs and treatments that will yield the greatest benefit to the patient.  

We will eventually see this type of therapy for all human illness and will likely have access to tests that will portend the future and enable patients to avoid developing conditions such as diabetes, heart disease, and various types of cancer. 

1. Paik, S. et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004.351; 2817-2826. 

2. http://www.lifetechnologies.com/us/en/home/about-us/news-gallery/press-releases/2012/life-techologies-introduces-the-bechtop-io-proto.html

Dave Fishman is President of Snowfish, LLC a strategic consulting firm which specializes in helping life sciences companies by using data to address the most challenging issues.  More information on Snowfish may be found at www.snowfish.net or by emailing us at info@snowfish.net.