SANTA CLARA, Calif.—Affymetrix Inc. and Signature Diagnostics AG of Potsdam, Germany, have signed an agreement that provides Signature Dx with a worldwide license to use Affymetrix's microarray technology to develop and commercialize diagnostic and prognostic colorectal cancer (CRC) tests.
Signature becomes the 13th participant in the Powered by Affymetrix (PbA) program, notes Roger Schaller, senior director of business development.
"Several of our partners are in some stage of discussions with the U.S. Food and Drug Administration (FDA), and three have received FDA clearance," Schaller says. "The first FDA clearance was for our PbA clinical diagnostics infrastructure, the GCS 3000 Dx v.2, and we're in the process of putting our GeneChip Human Genome U133 Plus 2.0 Array and our cGMP reagents through clinical trials. Among our partners, Roche was the first DNA chip cleared, Pathwork was the first RNA chip cleared and TessArae was the first resequencing test cleared; we hope to have the first cleared expression components soon. We are now better positioned to help our partners with the progress we've made in the development and in the regulatory environment."
Like Signature, all PbA companies are involved in human diagnostics. And they are all using some form of microarray technology—gene expression, genotyping, FFPE and/or resequencing for diagnostic discovery of biomarkers, to discover new tests, and/or develop companion diagnostic therapies. In the case of the Pathwork test alone, the company estimates the annual total available U.S. market as $600 million. This is calculated by multiplying the total market size of 150,000 cases by the list price for the testing service of $3,950. Pathwork's Tissue of Origin Test's penetration into that market will be driven by physician awareness, reimbursement and market share relative to competitive tests, says the company's vice president of commercial operations, Dave Craford.
CRC is the third most common cancer worldwide. In the five major European countries and the United States, approximately 396,000 individuals are diagnosed with CRC every year. Of these, 277,000 patients are diagnosed with stage II and stage III CRC. Approximately 30 percent of the patients with stage II and roughly 50 percent of those with stage III experience disease progression including distant metastasis of the liver and lung or local recurrence within three to five years after surgery. If the cancer spreads to distant organs, the five-year survival rate is only 8 percent.
"Colorectal cancer is one of the most common cancers worldwide and our innovative, multivariate in vitro diagnostic (IVD) tests can significantly improve both the diagnosis and prognosis of the disease," says Dr. Andre Rosenthal, CEO of Signature Diagnostics.
More than half a dozen companies have developed blood-based tests for early detection of colorectal cancer, Rosenthal adds. Some companies, e.g., Epigenomics (Germany) and OncoMethylome Science (Belgium), focus on a single methylation marker or a combination of two methylation markers that are detected in free tumor DNA that circulates in the plasma. The data published so far shows that both methylation tests have an overall sensitivity of 62.5 percent (Epigenomics) and 56 percent (OncoMethylome Science).
The sensitivity of the two methylation tests for Dukes A and B cancers is even smaller, Rosenthal says. Other companies develop tests that measure a small number of microRNA or RNA markers. For example, the test of GeneNews (Canada) combines seven RNA markers. While the GeneNews test has a higher sensitivity of 70 percent, it has an unacceptable low specificity of 72 percent.
"In contrast, our Detector C test comprises 202 RNA markers that are measured simultaneously in the white blood cells using the Affymetrix microarray platform," Rosenthal notes. "Our test is best-in-class. It has a validated sensitivity of 90 percent for all four stages of colorectal cancer, and a validated specificity of 88 percent."
In the United States and in the five major European countries, there are 170 million people aged 50 to 79 that should be screened for colorectal cancer, Rosenthal says.
"Even in the core segment of ages 55 to 69 years, more than 100 million people need to be screened," Rosenthal notes.
He adds that there is no way that this huge population can be served with an invasive and expensive method like colonoscopy. Besides compliance, such colonoscopy resources simply don't exist. "We believe that only a non-invasive, highly accurate blood-based test can lead to higher compliance rates of greater than 50 percent," he says. "We estimate that our Detector C blood test has blockbuster potential. Our revenue forecast shows that Detector C could achieve sales of $3 billion to $5 billion dollars at peak sales per year, starting in 2016 in the major markets."
"Signature Diagnostics' innovative colorectal cancer tests have the potential to vastly improve diagnosis and lead to better-informed treatment decisions for this disease," says Dr. Andrew Last, executive vice president and chief commercial officer at Affymetrix. "This agreement demonstrates the importance of microarray technology in advancing healthcare and further reinforces Affymetrix's leadership position in the global shift towards personalized healthcare. Array-based technologies can handle a lot of probes that relate to genes and do a lot more at one time to test for accuracy and sensitivity."
Microarrays were put through the rigors of the Microarray Quality Control Consortium (MAQC) to show that they are reproducible and accurate, Last says.
"They are proven to be useful in diagnostic applications and they allow you to get answers that you couldn't get before," he says. "Microarrays are carving new ground by allowing a dense number of probes to test hundreds to thousands of genes—the qPCR test can only test a handful. For example, one test developed by our PbA replaces six tests that were either time consuming, incomplete, suspect, or hit-or-miss results. Arrays answer all the questions it would have taken weeks to do, and you still would have come away with errors or subjectivity. We're talking two-day turnaround versus weeks, and if you've got leukemia, for example, you need answers now. We're talking about testing for lung or colon cancer by using a bronchial brush, nose swab or a little blood sample, versus invasive surgery or probes."
