Skyline Diagnostics recently gained a CE-IVD Mark for its AMLprofiler leukemia test, making it the fourth test based on the Affymetrix GeneChip platform to be launched in the US and Europe for clinical use since 2005.
And while the array maker's other diagnostic partners have pledged to introduce more tests, it is unclear when many of those assays will become available.
Roche secured US Food and Drug Administration clearance for its CYP450 AmpliChip for drug-metabolism screening in January 2005, becoming the first Affymetrix partner to launch a clinical assay on the GeneChip platform.
Redwood City, Calif.-based Pathwork Diagnostics was the second when its tissue-of-origin test received clearance in the US in 2008 (BAN 8/5/2008).
That year, Marseille, France-based Ipsogen launched in the EU its MapQuant Dx Genomic Grade, which uses a 97-gene signature taken from biopsies to measure tumor grade — a consensus indicator of tumor proliferation, risk of metastasis, and response to chemotherapy (BAN 12/2/2008).
Affy officially has so-called Powered by Affymetrix diagnostics agreements with a dozen partners. In addition to Roche, Pathwork, Ipsogen, and Skyline, the company includes Almac Diagnostics, BioMérieux, Epigenomics, Medical Prognosis Institute, Signature Diagnostics, Sysmex, TessArae, Veridex, and Vita Genomics on that list.
Not all of these companies are committed to bringing Affy-based tests to market, though, and it is unclear when those that do plan to launch array-based tests will realize their goals.
Craigavon, UK-based Almac, for instance, has been developing several tests for use on the Affy platform since it signed a PBA agreement with the company in 2005. The assay closest to commercialization is designed to detect colorectal cancer recurrence.
The firm has provided several potential launch dates in the past, the most recent going back to 2008. Two years later, Almac said the test, called ColDx, was in the final stages of validation and would be submitted for FDA clearance by early 2011 (BAN 6/15/2010).
This week Austin Tanney, Almac's scientific liaison officer, reaffirmed that the test is "entering its final validation."
Tanney told BioArray News that the firm has a number of other tests in its pipeline based on its own development and with partnerships with pharmaceutical clients, but that the final platform upon which these tests will be deployed depends on the number of genes in the diagnostic signature.
That being said, Tanney noted that a "number of the tests in development are likely to be best suited to a microarray platform," and that the platform would likely be Affy's. He did not discuss the other test indications.
Tanney called Affy's platform "ideal" for discovery, and noted his company has been using the company's arrays in its internal discovery programs.
"When it is appropriate to bring these tests forward on a microarray platform, it makes sense to bring them forward on the Affymetrix platform," Tanney said. "There have already been a number of FDA-approved tests developed on the Affymetrix platform and the platform itself is FDA-cleared."
German test developer Signature Diagnostics in June 2010 announced plans to commercialize its tests for colorectal cancer. The Potsdam-based Signature Dx initially planned to launch by the fourth quarter of last year two array-based in vitro diagnostics for colorectal cancer. In September 2010, Signature pushed back the launch of its tests to "early 2011" (BAN 6/29/2010).
Signature's tests are called Detector C and Predictor C. Detector C is a non-invasive, blood-based early detection test that evaluates the expression of 202 genes that are altered in response to tumor formation and growth. The Predictor C test evaluates the expression of 32 genes that predict disease progression in stage II and III colorectal cancer patients and has been shown to identify half of all stage II/III patients with a high risk of disease progression, the company said last year.
Elsewhere in Europe, Berlin-based Epigenomics has used the Affy platform for discovery work, but has since decided against using it as a diagnostic platform, according to Achim Plum, senior vice president of corporate development.
The company originally developed an assay on the Affy platform for PITX2 DNA methylation, an "independent prognostic factor in prostate and breast cancer", Plum noted.
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As late as last year, Epigenomics was seeking a partner to commercialize an array-based version of the test (BAN 3/30/2010)
This week, though, Plum told BioArray News that Epigenomics is "consolidating our test portfolio to run on one platform technology," namely real-time PCR. An RT-PCR assay for PITX2 methylation is currently being developed rather than the array-based test, he said.
"Originally we selected [the Affymetrix platform] as an alternative to RT-PCR to optimize our back royalty burden and have a platform that allows simultaneous measurement of multiple markers," Plum said.
"However, we in the meantime realized that usually one or very few DNA methylation markers allow answering a diagnostic question with very good sensitivity and specificity."
RT-PCR is therefore Epigenomics' current "method of choice, seeing its multiplexing capabilities, widespread use and acceptance, availability of numerous platforms with significant installed bases, ease of use, throughput, and reagent costs," Plum added.
While Epigenomics has turned to RT-PCR, Affy's other partners in Europe envision their array-based tests being employed as companion diagnostics.
Roche, for instance, has in the past discussed three additional Affy-based tests, including a AmpliChip for leukemia and a p53 AmpliChip for assessing response to cancer treatment, both of which the firm previously said could become available in 2009 (BAN 7/31/2007).
Last year, Roche announced that it would make the p53 AmpliChip available to Merck for use in its research programs (BAN 2/23/2010). The chip is designed to detect mutations in the tumor suppressor gene p53.
The test could potentially lead to better treatment outcomes for cancer patients by determining which patients would most likely respond to investigational drug candidates, Roche said at the time.
A Roche spokesperson told BioArray News this week that the AmpliChip p53 test is in "clinical development as a companion diagnostic to support novel compounds in development by Roche Pharma and Merck."
The product is currently not commercially available, he added, without elaborating.
Denmark's Medical Prognosis Institute is also looking to parlay its development programs into companion diagnostics. Last September, CEO Jon Askaa told BioArray News that the firm is developing a number of microarray-based tests that can determine which cancer patients have the greatest likelihood of benefiting from a particular drug (BAN 9/21/2010).
MPI's Drug Response Predictor pairs the company's algorithms and expertise with the Affy platform to help guide both clinical validation and patient treatment. The firm collaborates with Santaris Pharma, Roche Molecular Diagnostics, and AstraZeneca, according to its website.
MPI has other tools in development, including its Drug Sensitivity Predictor, which can help pharmaceutical companies identify indications for their compounds, and the Cancer Prognosticator to measure the aggressiveness of non-small-cell lung cancer tumors.
Askaa did not respond to an e-mail this week seeking an update on MPI's plans.
Affy's remaining partner in Europe, BioMérieux, has not provided an update on its plans since 2007, when it said it expected to develop a blood-based prostate-cancer screening test aimed at helping doctors weigh the risks of performing surgery to remove tumors. The company did not respond to an e-mail this week.
Like Affy's partners in Europe, the firm's three North American collaborators — Pathwork, TessArae, and Veridex — are also developing a series of tests on the GeneChip platform. At the same time, it is unclear when these diagnostics will reach the clinical market.
A spokesperson for Pathwork this week did not discuss additional diagnostics beyond the firm's TOO test. At the same time, the company seems committed to the Affy platform.
"Affymetrix microarrays produce highly reproducible gene-expression results and there is extensive literature documenting their use and successful application," the spokesperson said. "Also, Affymetrix has a proven ability to manufacture large quantities of high-quality GMP microarray chips. This is obviously important for Pathwork, given that our proprietary Pathchip microarray is a core component of our diagnostic test."
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Matthew Lorence, vice president of marketing, sales, and business development for TessArae, said that the company has used the platform to develop three different assays for infectious diseases, including one for viral and bacterial respiratory pathogens; one for pathogens of tropical and emerging infections; and one for viruses causing hemorrhagic fever, all of which run on the Affy platform.
Additionally, the Potomac Falls, Va.-based company has "several" GeneChip-based assays in development: one each for blood-borne pathogens; human retroviruses, all known food-borne pathogens; antibiotic resistance among sepsis-causing bacteria; respiratory infections in immunocompromised patients; pathogens associated with infectious encephalitis and meningitis; and infectious diseases found in swine.
TessArae also offers two genetic disease arrays for use in humans and has three more in development. Its offerings include tests for Noonan Syndrome and Periodic Fever Syndromes, both developed with Gaithersburg, Md.-based diagnostics firm GeneDx, Lorence said.
The ones in the pipeline include an 11-gene cancer/oncogene panel, a 95-gene recessive disease/allele panel, and a 43-gene neuropathic-syndrome panel.
"The genetic-testing applications offer sequencing of exon backbones of target genes for discovery of potentially pathogenic heterozygote loci as well as sequencing-based screening for known pathogenic alleles," Lorence said.
In terms of seeking regulatory clearance, Lorence said that TessArae has submitted its respiratory pathogen array for 510(k) clearance and is "working with the FDA on issues surrounding sequencing-based versus biomarker-based platforms for diagnostic tests." He did not elaborate.
While other technologies, including next-generation sequencing, are being adopted by some labs, TessArae maintains that arrays provide the "greatest informatic content for the price, with the greatest consistency in performance, and in manufacturing reproducibility," Lorence said. "These are critical features of the GeneChip platform that enable us to offer transformative, far more critically informative diagnostic capabilities to our customers."
Affy's third partner in the US, Johnson & Johnson unit Veridex, did not respond to e-mails seeking comment. Scientists from the company have in the past published papers on the use of array-based signatures in evaluating the prognosis of prostate cancer.
Beyond the US, Affy has PBA partnerships in place with Kobe, Japan-based Sysmex and Taiwanese molecular diagnostics-developer Vita Genomics. Neither firm responded to e-mails seeking information on their tests this week.
Vita Genomics CEO Ellson Chen told BioArray News in an e-mail in 2007 that the firm was developing two types of assays with Affy chips: One was to test for familial hypercholesterolemia while the other was being designed to predict patient response to patients with hepatitis treated with interferon-based combination therapy.
"We are offering them to patients in Taiwan and China through major hospitals using homebrew tests from our certified reference lab," Chen wrote at the time. "Once the market gets established, we do plan to file for FDA approval. It will most likely go through collaborations with a partner towards next year."
Roger Schaller, Affy's senior director of business development for clinical applications, told BioArray News this week that the firm is "committed to providing our partners tools for bringing these complex clinical tests to the market."
Such tools include "producing GMP-level arrays and reagents and submission of our expression reagents for FDA clearance to accelerate our partners' path to market," he said.
"Our partners are optimizing our technology to answer very complex diagnostic questions and this makes them true pioneers of applied personalized medicine," Schaller added. "Developing these tests are challenging, yet with our partners, Affymetrix continues our momentum in the clinical space."
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