Personalized Medicine, or PM, is a large umbrella term describing the use of patient information, usually genetic or biological, to tailor medical treatments that are specific to the characteristics of each individual. In 2009 an in-depth report by PricewaterhouseCoopers focused on the growing science of PM and pegged the market value of the field at $232 billion and projected a staggering growth rate of 11% annually to $452 billion by 2015.
With two recent announcements by Life Technologies (LIFE) and Oxford Nanapore on the development of new rapid and cost-effective DNA sequencing technologies there is no doubt that the age of Personalized Medicine is upon us and many companies in this space will forge forward and profit considerably while many will perish because their technologies are no longer the vanguard of modern technology.
As health care budgets force us to use more rational and efficient medications, PM will eventually be a standard of care. Imagine a scenario where a physician can take a sample of blood and quickly learn which of three drugs will work best with their patient's genetic makeup and produce the greatest benefit with the least amount of side effects ultimately saving precious treatment time and reducing costs.
Moreover, a report from the Hastings Center suggests patient costs associated with chronic disease are dramatically increasing. The report projects patient costs from diabetes and Alzheimer's alone to reach approximately $400 billion between 2015 and 2020. Thus, preventative uses of PM will dominate the market place as to offset the burden on health care budgets from sustained treatments of chronic diseases.
In this article I will provide a practical overview of the field of PM and provide examples of companies that represent the practice. In future articles, I will be highlighting different areas of PM and pointing out technologies and companies I believe will benefit most in this maturing frontier.
What is PM and why should we care about it?
The ultimate goal of PM is to utilize information about a person to rationally prescribe medicine in a tailored approach so that only the most effective treatments are used, thus increasing medical efficiency. In principle, medical practitioners have been using PM for quite some time. For example, a patient with a breast tumor that expresses the estrogen receptor (ER positive) may be given an estrogen antagonist, a drug that blocks the binding and activity of estrogen to the tumor. In contrast, there is no need to administer the antagonist to a patient when the tumor has no receptors to block. Reducing the probability of giving people treatments that are ineffective by virtue of their biological makeup not only speeds treatment time, but also has the potential to reduce side effects.
Whenever we are prescribed medicine it is because a physician has determined that the benefits of treatment will outweigh the disadvantages of the side effects. For most medicines this may not be a difficult decision because the side effects are nominal or merely discomforting. In the case of more serious diseases such as cancer, the side effects can be substantial. A drug may be the most effective and appropriate, but if the patient cannot tolerate the side effects the treatment must end early; many times these negative effects do not materialize until after treatment begins so prescribing drugs can be a process of trial and error.
The cost of treating side effects can be substantial, especially when they result from chemotherapy. For example, a study report form the 2011 European Multidisciplinary Cancer Congress indicated that the most expensive complications related to chemotherapy and/or anti-HER2 therapy were anemia, dehydration, dyspnea, and neutropenia. The individual cost per month resulting from these complications ranged from about $3,000 to $4,000. Thus, the side effects do not only interfere with the course of therapy, they can also dramatically increase the cost of treatment.
As the PM field matures, information made available to physicians before prescribing medicine is where PM will prove most advantageous. In principle, by using a blood test or biopsy, a practitioner would be able to identify if a patient would better respond to a particular drug and determine if a drug will produce side effects in a particular patient before they start treatment.
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Figure 1. Genes are DNA sequences that code for a protein, and many proteins are enzymes that metabolize drugs. In this example, patient subset B has a genetic mutation or Single Nucleotide Polymorphism, SNP, as indicated by the asterisk. In these patients a drug could be under or over metabolized creating less or greater drug potencies, respectfully. Physicians want to biologically screen patients to identify individuals that would respond optimally to a drug.
What are some examples of companies developing PM?
Using a PM approach in the clinic requires acquisition of knowledge on many fronts, including building large databases of genes and their corresponding proteins, metabolites and mutations. Further understanding will require discovery of how drugs and foods interact with genes and their mutations. It is one thing to identify a mutation or a change in a gene sequence, but it is another entirely to know exactly what these differences mean in terms of a biological response.
Understanding the interactions of genes and their products with drugs can be described as the field of genomics, which includes proteomics and metabolomics, pharmacogenomics and nutrigenomics. The later two fields deal with the study of genes and their effect on the response to medicine and diet, respectively.
Figure 2. Personalized Medicine mainly relies on the study of genomics to predict drug effects in specific patients. Targeted therapies can also fall in this category because many times a drug is designed to target a specific receptor or physiological property of the diseased tissue. Patients with a particular drug receptor, for example, would be given a target-specific drug while others without the receptor would not. PM thus improves medical efficiency by optimizing prescribing so only the most effective drugs are used on a patient, thus reducing side effects and their associated costs.
The vastness of the genome, proteome and metabolome is so great that it is difficult to gain and apply information in a practical way. The cost and time it takes to sequence a meaningful length of DNA has long been a barrier that companies now are beginning to overcome. LIFE recently announced the Ion Proton Genetic Sequencer, a technology that can sequence the entire human genome in a day. The machines will cost under $150,000 and samples can be processed for around $1,000, which is a price range I believe many people would be willing to pay to have their DNA sequenced.
With a device cost of less than $150,000 every hospital and clinic will want to purchase one to improve their patient care and practice efficiency. A private company, Oxford Nanapore, is taking device size and sequencing speed to new limits and have just announced a device the size of a thumb drive that can read DNA right from blood, and a second device so efficient that if 20 of them are used simultaneously, you will be able to sequence the entire human genome in 15 minutes for around $1500.
These technologies are obvious breakthroughs and will allow for the rapid identification of gene sequences from different patients, tumors and other disease states. It will significantly ramp up the discovery and treatment process over the coming years. I am very positive in regard to the future of PM, but even with these breakthroughs there is a long way to go in using the collected data in the clinic to actually produce improved patient outcomes. When the full potential of PM is reached, the field of medicine as we now know it will cease to exist.
In the immediate future another type of PM is taking shape in the form of targeted therapies, where specific diseased cells in the body are targeted. Targeted therapies are not traditionally included in the arena of PM. Although, I feel it is appropriate to include them because these therapies usually rely on targeting specific tumor markers or on the physiological properties of diseased tissues, such as the neovasculature or the amount of tissue hypoxia (low oxygen levels).
Figure 3. Many targeted therapies take advantage of the differences between diseased tissue compared to normal tissue. In this example of targeted therapies normal tissue is fully oxygenated. Many therapeutic pro-drugs are inactive (non-toxic) in the oxygenated areas and become active (toxic) in the hypoxic areas, such as in tumors. The vasculature of tumors is "leaky" and may allow the specially formulated drugs or carriers to accumulate in the tumor and increase toxicity, while sparing normal tissue with well-formed efficient vasculature.
An example of a targeted therapy is TH-302 by Threshold Pharmaceuticals, Inc (THLD). The drug targets hypoxic areas of tumors, which are more resistant to therapies such as radiation. Merk KGaA has recently entered into an agreement with THLD to co-develop and commercialize TH-302, which is now in Phase 3 clinical trials. Drug delivery using engineered molecular carriers is another exciting variation. Nektar Therapeutics' (NKTR) NKTR-102 is in clinical development for various cancers. This macromolecule therapeutic is administered as an inactive compound and is slowly activated.
The drug has a significant increase in half-life compared to first generation drugs targeting topoisomeriase I. Pre-clinical studies showed the drug accumulated within the tumor, presumably through penetration of the compromised or "leaky" tumor vasculature. This tumor specific delivery and high drug concentration within the tumor could help maximize tumor toxicity and minimize toxicity to normal tissues.
Not all targeted therapies work using the same mechanism of action and some can be associated with increased side effects; a recent clinical study found that some targeted therapies could increase treatment costs. The cost of treating the dermatological side effects related to targeted cancer therapy was approximately $2000 per patient. These studies do not apply the full genomics component that PM affords and future research could bring more understanding as to which patients will have the most side effects.
A refined combination of PM with targeted therapies could bring about a new level of ultra-PM where knowing more about the genetic makeup of the patient could take advantage of the differential of targeted therapies and aim to exploit individual genomic profiles to maximize therapeutic outcomes. In the end the goal is the same- improved drug efficacy and reduced side effects.
Diversification within this field is particularly important and an ETF in this space is an excellent tool to accomplish that goal. The PowerShares Dynamic Biotech & Genome Portfolio (PBE), for example, contains companies that focus on genomics and targeted therapies, as well as contains a diversification of companies with non-PM drugs such as those competing in the lively Hepatitis C treatment arena.
I find PM to have a promising future, especially when we consider the potential for compounding the sophistication of genomics with the specificity of targeted therapies into ultra-PM.