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A companion in your corner (Part 2)
This story is a continuation of Part 1. Click here for the other half of the story.
It's not a tumor
Cancer is not the only therapeutic area receiving attention from the companion diagnostics industry, although the predominant approach is still genomics.
In January, the FDA approved Vertex Pharmaceuticals' Kalydeco, a new drug for the treatment cystic fibrosis (CF), but only in patients with a specific mutation (G551D) of the CFTR protein, which is much rarer than the F508 mutation commonly seen in CF patients. As part of the drug's label, the drug cannot be given to a patient until the presence of the G551D mutation is known using either existing knowledge or the use of an FDA-cleared CF mutation test, such as Luminex's xTAG Cystic Fibrosis Assay. By July, the drug was also approved for use in Europe, and ongoing studies are showing efficacy in patients with the F508 deletion mutation when used in combination with the company's investigational compound VX-809.
Infectious disease is also seeing an increasing interest from the companion diagnostics market. In February, Erlangen, Germany's Siemens Healthcare Diagnostics announced a partnership with ViiV Healthcare of Brentford, U.K., to focus on clinical trials related to Selzentry (maraviroc), the latter 's CCR5 co-receptor antagonist for use in select HIV patients. As part of ViiV's Phase III trial, Siemens will provide genotyping expertise that it hopes will lead to an FDA-approved test.
Similarly, in June, San Diego's Millennium Laboratories announced its introduction of Millennium Pharmacogenetic Testing (PGT), a saliva-based test targeted at genetic variations in enzymes associated with medications commonly used in patients with chronic pain. The goal is to ensure patients not only receive drugs that effectively ameliorate their pain, but also help identify patients who could experience unpleasant side effects.
Whether PGT becomes a true companion diagnostics or just another tool in the clinical arsenal remains to be seen.
Of course, as noted, companion diagnostics aren't just about putting the right patient on the right drug, they can also be about making sure the right patient gets the right amount of a drug or that specific patient populations are monitored for undesirable side effects that may occur more frequently.
The granddaddy in this category is warfarin. Recognizing the impact of genetic profile on how patients metabolized warfarin, the FDA issued new guidance in 2007 on the use of genetic testing to help determine the appropriate dose of warfarin, allowing for efficacy while limiting the risk of excessive bleeding. The forms of the CYP2C9 and VKORC1 genes a patient carries have significant impact how he or she responds to a given dose, so the drug's labeling was updated to reflect the importance of genotype information in patient dose selection.
What's true for warfarin may also be true for Plavix. Last November, Jessica Mega and colleagues at Brigham and Women's Hospital in Boston presented their findings on the possible role of patient genetics in their response to treatment with Plavix. Looking strictly at platelet function (rather than clinical outcomes), the researchers found that patients carrying one mutant version of the CYP2C19 gene required up to threefold as much daily Plavix (225 mg) to show the same effect as other patients showed with the standard dose (75 mg). Furthermore, patients carrying two mutant versions of the gene did not show the same response at the highest dose tested.
"It appears that it is only patients who are homozygous CYP2C19*2 carriers—and these make up only 2 percent of the population—who are really difficult to treat with clopidogrel (Plavix), and they probably do need to be treated with one of the other agents—prasugrel (Effient) or ticagrelor (Brilinta)," explains Mega.
Whether this information might lead to any labeling changes for Plavix or changes in clinical practice by physicians is hard to say. Mega acknowledges that at the time, testing required sending samples off, which may put physicians off, but she strongly believed that this was an important consideration in dosing decisions, alongside the more typical clinical characterizations.
The University of Florida-Gainesville's Lawrence Lesko added his voice to the conversation, stating: "I've been both a patient and a scientist. There is a clinical utility that is generally speaking to the population benefit of doing the test. And then there is the personal utility: what this test means to me. If I were a patient, I'd very much want this genetic test if I were going on Plavix today."
Already, companies like Santa Fe, N.M.-based Matrix Genomics are offering consumers the chance to have their CYP2C19 status tested, as well as markers for response to warfarin and tamoxifen and a variety of medical conditions such as depression, Alzheimer's and Parkinson's.
Tomorrow never knows
How rapidly companion diagnostics become the norm for drug approval and eventually for patient prescribing is an open question, but it seems to be inevitable in one form or another.
"Looking at flow of diagnostics tests performed in a pathology lab today I could also foresee a significant change in favor of companion diagnostics," offers Dako's Winther. "In my opinion, I could easily foresee that in seven to eight years' time, you will see no oncology drug being prescribed without having a companion diagnostics attached to it."
Whether for oncology or to simply ensure the safest doses are being prescribed, the advent of companion diagnostics should be a significant comfort to patients like Dorothy, who, by the way, recovered fully from her mishap and lived another decade or so, thanks to her healthcare team and therapeutics.