Companion diagnostics: marrying test with treatment
Patrick Groody, PhD
Like the computer, the automobile, and the cheeseburger, medicine is becoming tailored more and more to the individual. However, while the first three are personalized with regard to a customer’s tastes, treatment options are personalized with regard to a person’s genetic makeup. The goal of this kind of personalized medicine, known as companion diagnostics, is to “use a diagnostic test along with a therapeutic to make sure you’re getting the right drug to the right patient at the right time,” says Pat Groody, PhD, divisional VP of research and development, Abbott Molecular, Abbott Park, Ill. “It really is marrying those two technologies in order to tailor a specific patient’s therapy in order to maximize the likelihood of a positive outcome.”
The development of a diagnostic tool begins with the discovery and understanding of the basic biology or pathway that plays an important role in, for example, a particular tumor type. Once that pathway has been understood, a pharmaceutical company might develop a new pharmaceutical agent to interrupt that pathway in such a way that it might have a positive impact as a cancer therapy. At this juncture, companies such as Abbott step in.
“What our tests can do is identify or detect the biomarker that may be a critical part of that pathway,” Groody says. “For example, a particular genetic mutation might result in something along that pathway to go in an undesired manner. So we develop a test that can detect that genetic abnormality. When a patient is diagnosed with cancer, we can look at a particular tumor type for that particular genetic abnormality, and when we find the abnormality, those might be the cases where a patient might be a good candidate for that targeted therapy.” A perfect example is Abbott’s Vysis® ALK test, which detects a gene rearrangement in advanced non-small-cell lung cancer patients, who then may be eligible for treatment with Xalkori®, an oral ALK inhibitor.
For Groody, companion diagnostics constitutes more than the tests that uncover a person’s genetic profile. “There are other molecular diagnostic tests that are important in monitoring the effectiveness of therapy and may be considered companion diagnostics in a sense,” he says. “If you look at our RealTime HIV or HCV viral load assays on the m2000™ System, we monitor patients once they are put on a therapy and we are looking for a change in the amount of virus present. In the event we would see that increase, we would conclude that the therapy they are currently on is no longer effective, which would indicate time to change therapy.”
The field of companion diagnostics is still relatively new to most medical facilities. “Eight or 10 years ago, there really wasn’t routine use of molecular testing,” Groody says. “The methods used were complicated, there was limited instrumentation available, and there were a limited number of people who were able to do it routinely.” With the advent of new equipment (such as Abbott’s m2000 System) that could be implemented in hospitals and reference labs, the molecular testing field has grown. “The automation of the sample prep and the amplification part of the testing has allowed us to drive the technology into routine use in hospitals,” he says.
The technology is catching on. According to Groody, the m2000 System has more than 1,200 placements in virtually all parts of the world. “You’re beginning to see more and more hospitals getting involved in molecular testing, not just because it’s becoming easier to perform, but because it’s becoming more a part of the way we treat and manage patients,” Groody says. For now, the acquisition of this equipment depends on the size and throughput of a lab, among other things. But as the technology becomes increasingly automated and ingrained in the underlying principles of medical treatment, more labs will be incorporating molecular diagnostics into their standard array of tests.
Abbott Molecular’s most successful “true” companion diagnostic products are focused in oncology, including the Abbott Vysis ALK Break Apart FISH Probe Kit for non-small-cell lung cancer and PathVysion HER-2 DNA Probe Kit for breast cancer, both of which utilize fluorescence in situ hybridization (FISH) technology and were developed in tandem with a pharma partner. More and more, future development will focus on developing tests for a more automated platform, such as Abbott’s m2000 System.
Rapid change is common with emerging technology. Companion diagnostics is no different. For one, the scope of testing possibilities will grow and advances in diagnostics, imaging and drug delivery are helping treat patients with greater speed, accuracy, and efficacy. Currently, oncology is the area in which companion diagnostics are used most frequently. “Oncology has the greatest need if you look at the effectiveness of treatment across multiple disease states,” Groody says. “Oncology typically ranks at the lowest end of that, with less than a quarter of treatments being effective.” But companion diagnostics could potentially pair with any pharmaceutical or therapy to make them more effective. With that in mind, one of Abbott’s challenges is deciding where to invest its resources. Looking forward, Groody says he expects HCV, neurosciences, and cardiovascular to be important areas for future applications.
Groody anticipates a fundamental shift in thinking will take place as the field of companion diagnostics grows. “As our ability to develop multiplexing grows, I think it will be better for us to ask the broader question—not ‘Does the patient have this?’ but instead ‘What does the patient have?” he says. “The landscape and behaviors that will allow personalized medicine to flourish are just beginning to take shape, and they require both short- and long-term vision.”
By collaborating with major research universities and pharmaceutical companies, companion diagnostics has a unique standpoint from which it engages health care. It is not used to treat patients directly. Instead, it is used to refine the understanding of patient and treatment.
“In my 20, 30 years of experience, this has been the most exciting thing I’ve worked on,” Groody says. “If you look at it from a technology standpoint, it’s fascinating. And if you look at the unmet medical needs we’re addressing, if you’re talking about oncology, less than 25% of treatments being effective—having the opportunity to double or triple that, it says something about the value and importance companion diagnostics have on improving patient outcomes.”
Kurt Woock is associate editor for CLP.
