Eleven years ago, the Human Genome Project drew headlines when scientists, after more than a decade of labor, for the first time comprehensively mapped out a complete set of approximately 20,500 human genes. The cost? Nearly $3 billion.
Today, that same procedure can cost less than $1000 in a matter of hours. And that dramatic improvement in cost and speed has set the stage for a new kind of medicine called “pharmacogenomics.”
Pharmacogenomics is a facet of the broader trend colloquially dubbed “personalized medicine,” which provides “the right patient with the right drug, at the right dose, at the right time,” according to the U.S. Food and Drug Administration’s website.
This evolving field of medicine studies how different variations in DNA govern the patient’s drug response. The advent of “Next-Generation Sequencing” (NGS) technology expedited what had been the tedious process of extracting genetic information and sequencing individual genomic DNA. It has made it possible for doctors to tailor treatment for health problems including cardiovascular disease, cancer and HIV/AIDS based on a patient’s genetic profile. As pharmacogenomics gain wider implementation, the new science has the potential to alter the landscape of the $1 trillion global pharmaceutical industry and transform health care.
“Increased computational power and the advent of mobile and wireless capability and other technologies, are allowing patients to be treated and monitored more precisely and effectively and in ways that better meet their individual needs,” Margaret Hamburg, commissioner of the FDA, wrote in an October 2013 report.
Currently, physicians prescribe medication for their patients, based on the symptoms they display. If the medication fails to alleviate the condition, the physician tries a different medication, hoping for a better result.
“The drug responses can be anything from the ability of the drug to produce its desired effect, or the ability of the drug to cause an adverse reaction,” said Dr. Alfred George, department chair of Pharmacology at Northwestern University Feinberg School of Medicine in a phone interview.
This trial and error approach leads to rising health care costs and dissatisfied customers. It also often results in negative side effects and interactions, in turn causing patients to stop adhering to treatment regimens or, in extreme cases, serious adverse events including allergic reactions, internal bleeding or death. The FDA estimated 2.2 million adverse drug reactions each year, including more than 100,000 deaths, indicating much room for drug improvement based on overall inefficacy rates.
Pharmacogenomics is based on the premise that certain medications can be more or less effective in part depending on the patient’s unique genetic profile. New advances may soon allow doctors to prescribe medication that otherwise would not have been commercially available without the genetic data.
Oncology is the first major application for personalized medicine, according to Morgan Stanley analysts. Annual global spending on oncology drugs reached $91 billion in 2013, and is currently approaching $100 billion, according to IMS Institute for Healthcare Informatics data.
Unfortunately, an average of 75 percent of cancer drugs and 70 percent of Alzheimer’s drugs are ineffective, according to a Personalized Medicine Coalition report.
Currently, NGS has a tiny presence in the field and is used in a minority of patients, approximately 5-10 percent. Industry analysts estimate the potential opportunity for NGS in cancer applications alone could be an additional $10-$15 billion annually, before considering any uplift in associated drug sales.
“The latest cancer therapies can cost over $10,000 per month and surgical treatments can cost over $100,000 per patient, creating a powerful incentive for investments in better diagnostics to assess the prognosis for any given cancer and which patients will benefit most from a given therapy,” Morgan Stanley & Co. LLC analyst Steve Beuchaw wrote in a Sept. 8 research note.
In addition to cancer diagnostics, industry analysts anticipate additional potential addressable NGS opportunities in prenatal screening, immunogenetics and other applications, as well as in other therapeutic areas including cardiovascular and infectious diseases.
Personalized medicines rely heavily on the identification of “biomarkers” and successful development of companion diagnostic tests. Biomarkers are scientifically measured characteristics that indicate a biologic process, disease or response to therapeutic intervention. They help doctors evaluate and identify the stage of a disease and predict patient response to a treatment by using in vitro Companion Diagnostic devices, which test patients for individual differences at the genetic level.
These tests complement therapeutic products by letting healthcare providers identify patients for treatment, or others who should not receive particular treatment because of risks for an adverse side effect.
“The era of personalized medicine, has clearly arrived,” the FDA said in a report last year. Recombinant protein therapeutics, or “biologics,” which are linked closely to the personalized treatment format, are the fastest growing sector in the pharmaceutical industry and are increasingly used to treat some of the most complex medical conditions, according to the report.
The possibility of adopting personalized medicine proliferated after the FDA approved biotechnology company Illumina Inc.’s four diagnostic devices for NGS applications in November 2013. The devices interpret large sequences of DNA in a single test and are approved for use by physicians at the point of care, as opposed to shipping samples to a specialized laboratory. Two of the approved devices are used to detect gene variants for cystic fibrosis, a disease that affects the lungs, pancreas, liver and intestines.
“We look forward to continuing to build on the success of the HiSeq product family as we empower our customers to unlock the power of the genome,” said Kirk Malloy, senior vice president and general manager of Life Sciences at Illumina, in an Oct. 17 press release. Illumina stock prices have soared more than 250 percent within the past two years, driven in large part by the increasing adoption of NGS by physicians in addition to researchers. Academic centers are increasing NGS volumes in the clinical setting 30-50 percent each year, according to a Sept. 8 Morgan Stanley note.
The race to develop diagnostic tests is heating up as the FDA issued guidance on August 6, encouraging development of genomic-based therapeutic products and diagnostic devices. However, this is not an easy task.
“FDA approval is costly and unpredictable process,” Stifel Equity analyst, Miroslava Minkova, wrote in an Aug. 11 research note. “FDA approval typically requires large clinical trials, which take time to run and the outcomes of which are difficult to predict until trial results are reported.”
Initially, some pharmaceutical companies may have avoided pharmacogenomics because the science essentially segmented their market. “A drug that they would give all patients would suddenly only be given to a fraction of those patients,” explained Dr. Roland Valdes, chief executive officer of PGXL Laboratories, in a phone interview.
“They fought this tooth and nail for years,” he added. But eventually, he continued, the industry “ recognized that this would actually give benefits not only for patients, but for the pharmaceutical industry because they would take some of the drugs that in the past have not worked during clinical trials, and they could then target specifically which are the drugs that a certain group of people this would benefit.”
According to the company, PGXL was one of the first lab CLIA (Clinical Laboratory Improvement Amendments)-certified specifically to offer commercial pharmacogenetic tests, and many other companies are following suit.
The prospect of better-focused drug trials could save large sums of money, experts say.
“If you designed a clinical trial in a more intellectual manner, knowing about what’s important in terms of genetic variance, then you would obviously reduce costs as opposed to testing the drug on everybody,” said Dr. Eileen Dolan, an oncology professor at the University of Chicago, regarding pharmaceutical companies in a phone interview.
Today, “a lot of pharmaceutical industries are starting to embrace pharmacogenomics as an opportunity for them to develop a companion diagnostic test, to pre-test patients to see if they’re going to succeed in their drug or not,” Northwestern’s Dr. George said.
“The applications for NGS are becoming broader as the technology evolves and becomes more efficient, but the clinical validation and cost effectiveness analysis required to drive adoption more broadly is likely three to five years away,” Morgan Stanley analyst Beuchaw concluded.
Although NGS represented a leap forward enabling pharmacogenomics and personalized medicine, there is also much more for the field to learn about the intrinsic nature of diseases and biologic pathways in order to gain broad acceptance in clinical practice.
Lack of “knowledge about what [genomic] data the physician needs and how a physician needs to change the prescription based on the knowledge they gain from the genotype,” remains a large challenge, Dolan said in a phone interview.
In addition to the regulatory and scientific challenges that remain, the model for payment reimbursement and insurance coverage for genetic testing remain uncertain.
“I think there’s going to have to be some proof that that’s a cost-effective strategy to convince insurance companies that it’s worth paying for,” Dr. George said.
“I don’t think that’s a hard sell,” he added. “If they can do preemptive genetics and avoid costly adverse drug effects or poor drug responses that keep people in the hospital longer, that might actually tip the balance.”
As insurance companies warm up to pharmacogenomics, doctors on the field also recognize its impending impact in healthcare.
“For cancers, all tumors will be checked for mutational analysis, and therapy will be tailored to [pharmacogenomics],” Dr. Rachel Mitchell, a hematology and oncology fellow at Rush University Medical Center, said in a phone interview.
At present, she said, “we are sending the mutational analysis, but we just don’t know exactly how to utilize the information. As research progresses, I think this will be more useful.”
Greater understanding about variations in the human genome has ushered in an era of personalized medicine, but scientists still seek to deepen their understanding of each unique molecular signature in order to maximize the benefits for healthcare.