NUREMBERG, Germany — An Affymetrix executive this week affirmed the company's intention to submit its CytoScan HD to the US Food and Drug Administration by the end of this year, and said that it will have the product certified as an in vitro diagnostic in Europe in the same time frame.
"We still plan to submit [CytoScan HD] to FDA by the end of this year," said Andy Last, executive vice president of Affy's genetic analysis and clinical applications business unit. "Once we submit we will have completed our full package, all of our clinical trials, and so then we will start moving quickly to [obtain] CE-IVD certification," he said.
Last discussed the regulatory path for CytoScan HD at the European Society of Human Genetics meeting, held here this week.
Affy launched CytoScan HD last year. The array includes more than 2.6 million copy number markers, of which 750,000 are genotypeable SNPs and 1.9 million are non-polymorphic probes. Affy markets the tool for both constitutional and cancer cytogenetics research, but it is seeking regulatory clearance for CytoScan HD to be used for clinical constitutional cytogenetics. The firm originally hoped to submit the product to the FDA by midyear, but recently pushed its anticipated submission date back to "late 2012," citing an FDA request to adjust its clinical protocols (BAN 5/8/2012).
According to Last, obtaining FDA clearance for CytoScan HD is Affy's "most important" goal. He noted that while the company plans its submission for late 2012, it is still unclear when CytoScan HD might achieve FDA clearance. But, as the submission package will be ready by that time, and CE-IVD is a self-certification process, it is possible that CytoScan HD will be marketed for clinical use in Europe before it is in the US.
"FDA approval will be dependent on what the FDA determines when they see our package, whether they have further questions or not," said Last. "If it goes through FDA quickly, there will be little time difference between getting FDA clearance and CE-IVD, but if not, it may take longer to get FDA clearance," he said.
Affy — as well as Agilent Technologies and Illumina — signaled their intent to seek FDA clearance for their cytogenetic array platforms after the agency indicated two years ago that it would require labs that offer array-based chromosomal analyses to use cleared tests (BAN 7/6/2010). However, the terms of the submission process are unclear. If Affy does submit CytoScan HD to the FDA by year end, it will be the first of such tools to be reviewed by the agency.
CytoScan HD is an important product for Affy. During the firm's first-quarter earnings call in May, CEO Frank Witney said that by the end of 2012, the company expects CytoScan HD sales to account for 10 percent of its revenues (BAN 5/8/2012). While it is unclear how close Affy is to meeting that goal, Richard Shippy, director of marketing for clinical applications at Affy, said that "more than 100 users" have adopted CytoScan HD since its launch in July 2011. Shippy also spoke to BioArray News at the conference.
Affy's ambition is to be the number one player in the cytogenetics array market, but Agilent Technologies, which manufactures arrays for a number of other firms, including Oxford Gene Technology and BlueGnome, continues to be the dominant company. The firms' offerings are different. Agilent makes comparative genomic hybridization arrays containing select SNP content. Its highest resolution chips contain a million markers. Affy's 2.6-million-marker arrays offer a higher-resolution look at the genome — indeed the firm is marketing the array as the "Resolution Revolution" — but in order to gain the upper hand in the market, Affy must convert Agilent users who are comfortable with the lower-resolution CGH+SNP arrays.
"There is a natural tendency [to be] content," said Shippy of CGH+SNP array users. "Change is difficult in many situations and you have to have a significantly better alternative to overcome the natural barrier of being content with technology," he said.
Last said that potential customers typically have to see the "incremental value" of CytoScan HD via publications, seminars, and other outlets before they decide to take a chance on a higher-resolution array.
"There is this kind of, 'Wow, what do we do with all that data?' mentality" in the market, Last said. "But once people have seen it, it's like once you have seen BlueRay Disc, you don't want to go back to a DVD," he said. "And it is the same reaction we have seen among customers."
Shippy added that CytoScan HD's high SNP content can offer users advantages beyond the detection of uniparental disomy and loss of heterozygosity events, such as the ability to measure global mosaicism. "You can't do that on a 60,000-marker CGH+SNP array," Shippy said. "But customers are not often aware," he said. "They are hearing marketing from [other companies about] arrays [that] have lower density SNP, and [those companies] are promoting UPD and they are not promoting other attributes because they cannot achieve those attributes on their technology."
CytoScan and OncoScan
While much of Affy's focus appears to be on constitutional cytogenetics, the company is also eager to see its arrays adopted for cancer cytogenetics testing. A number of competitors have launched arrays that are specifically focused on cancer cytogenetics (see related story, this issue), but Shippy said that CytoScan HD provides as informative data on some cancer samples as it does on constitutional samples, but not all.
"In hematological malignancies in particular, where you have an abundance of material as you are dealing with blood or DNA … CytoScan is extremely attractive, because you are able to get a genome survey for copy number and LOH," said Shippy.
For the interrogation of solid tumors or older, formalin-fixed, paraffin-embedded samples, Affy recommends that customers use its OncoScan platform instead.
"For liquid tumors CytoScan HD is proving to be a very viable tool; for solid FFPE, it is not qualified yet, so OncoScan would be best," said Last.
Affy launched the second version of its OncoScan assay as a service last year. The array offers coverage of tumor suppressors and oncogenes and is marketed to users for the analysis of DNA from FFPE tissues to extract retrospective clinical data from archived samples. Affy has also claimed the assay can yield copy number, allelic ratio, and somatic mutation data from 75 nanograms of input DNA (BAN 4/15/2011). Affy aims to launch a kitted version of the product in early 2013.
Shippy noted that there are a number of labs that are using CytoScan on FFPE samples that are less than five years old, but Last said that CytoScan is "not qualified" for "aged" FFPE samples.
"If you have an abundance of DNA, and copy number and LOH are the two vehicles you want to measure across the genome, then CytoScan is the appropriate tool," said Last. "If you have degraded material or old material, and if you are interested in somatic mutations, as well as copy number and LOH, then OncoScan is the optimal tool," he said.