Sustained by a recent study that showcased its ability to identify recurrence risk of colon cancer, New York-based molecular diagnostics firm ChipDX is moving ahead with plans to eventually debut at least four microarray-based assays for the clinical market.
CEO Ryan van Laar told BioArray News this week that the two-year-old company currently has in its pipeline tests for colon, breast, lung, and tissue of origin cancer identification.
All of the tests run on the Affymetrix GeneChip platform and rely on an internally developed algorithm.
The most advanced of these assays is a gene-expression signature that the firm claims can accurately identify the risk of colon cancer recurrence.
In a study published this month in the British Journal of Cancer, ChipDX discussed how the 163-gene signature test stratifies colon cancer patients into high- and low-risk recurrence groups.
ChipDX developed its prognostic algorithm by analyzing data from a 2009 study of 232 US-based colon cancer patients. The company later used an independent validation set of 60 stage II and III Australian colon cancer patients to validate the discovery.
Both studies used Affy's GeneChip Human Genome U133 Plus 2.0 array profiles of colon cancer patients.
Van Laar said the BJC paper "demonstrates the significance of the 163-gene signature in identifying high-risk, early-stage patients and also its potential for delivering [in vitro diagnostic multivariate index assay] services via an online interface."
According to van Laar, the "originality of the paper comes from the fact the signature was generated from human tissues, validated on colon tumor only … from patients with stage II or III disease and results in a prognostic index that is continuously associated with outcome."
He said that ChipDX is "hoping to establish collaborations with organizations interested in participating in future validation studies, using either fresh-frozen or formalin-fixed, paraffin-embedded colon tissue."
According to the US National Cancer Institute, 103,000 individuals will be diagnosed with colon cancer in the country this year.
In approximately 20 percent of patients with stage II disease, or 20,600 individuals this year, the disease is expected to recur within five years.
Van Laar said that ChipDX hopes its predictive gene signature will "help doctors to identify early-stage high-risk patients and offer them more personalized treatment options based on a set of genes related to survival above and beyond traditional assessments of outcome." He did not elaborate.
Currently, ChipDX is making its colon cancer stratifying assay available for research use only through its website and is reviewing regulatory requirements and looking for partners to market it for future clinical use.
Van Laar declined to discuss a timetable for obtaining regulatory clearance for the test. However, he said that ChipDX has "received feedback in regards to the path forward for our tests" in the form of two pre-investigational device exemption reviews by the US Food and Drug Administration's Center for Devices and Radiological Health.
"We are actively incorporating [the FDA's] suggestions into our future plans and hope to establish strategic collaborations with interested parties in order to proceed," van Laar said. "We will also be working closely with Affymetrix to develop a custom ChipDX GeneChip, manufactured under appropriate conditions for IVD use."
Affy's role as a manufacturer of FDA-cleared microarray-based tests was one of the reasons ChipDX chose it over other array vendors. For instance, ChipDX decided against using Agilent Technologies' platform technology, though van Laar worked at Agendia as a senior bioinformatician from 2005 to 2008. Agendia's tests are manufactured by Agilent.
[ pagebreak ]
Describing ChipDX's decision to choose Affy, van Laar cited a "history of being used by FDA-cleared, in vitro diagnostic applications," the company's "global availability and familiarity" and the "wealth of [existing] publically available, clinically annotated tumor datasets."
By deciding to use the GeneChip platform, ChipDX joins around a dozen other firms that are looking to deliver array-based tests to the clinical market on Affy chips.
In addition to its colon cancer test, ChipDX is moving forward with three other diagnostic programs, including tests that are currently being developed for breast and lung cancers, and for tumor of origin identification.
According to van Laar, the firm's ChipDX Breast Cancer Module is based on a 200-gene algorithm designed to predict recurrence and survival in patients with early-stage breast cancer.
The panel was developed "with similar methods" as the colon cancer signature, "and has been validated on an independent multi-center, multi-platform cohort of over 1,000 patients," van Laar said. He added that a manuscript describing this work has been submitted to an undisclosed peer-reviewed journal focused on molecular diagnostics.
The second of the three other tests, for lung cancer, was described by van Laar as "nearing the final stages of development." He said the firm's algorithm has "been designed to address some of the shortfalls of previously published non-small cell lung cancer signatures" and has been validated on more than 500 lung adenocarcinomas, which were profiled in "multiple locations using multiple genomic platforms."
Finally, the firm's Tumor Origin Module "differs from the other modules" in that it is designed to predict tumor origin, rather than patient prognosis, van Laar said. Both Agendia and Pathwork Diagnostics currently offer array-based assays for identifying tissue of origin in cancer patients, though van Laar did not mention these firms.
ChipDX's test could "assist clinicians in diagnosing tumors of unknown origin or those that are poorly differentiated and difficult to diagnose using traditional means," van Laar said. ChipDX is hoping to present data on the assay at the American Association of Cancer Research in Orlando, Fla., next April.
He added that the Tumor Origin Module could be used as a quality control for the company's other assays, "specifically in ensuring the genomic profile being analyzed does actually represent the correct type of tissue."
In that scenario, the tissue type of each sample analyzed by the colon, breast, and lung modules would first be confirmed by the Tumor Origin module, van Laar said.
Have topics you'd like to see covered in BioArray News? Contact the editor at jpetrone [at] genomeweb [.] com.