Pathwork Diagnostics last week said that the US Food and Drug Administration has given its array-based Tissue of Origin test 510(k) clearance, and that it is now free to market the test to clinicians in the US.
The TOO test, which determines what type of cancer cells are present in a malignant tumor, measures the expression of more than 1,500 genes to compare a tumor’s gene-expression profile to those of 15 known tissues. These tissues represent more than 60 morphologies, and Pathwork claims the test can provide an objective, probability-based score for each potential tissue. The test runs on Affymetrix’s GCS3000Dx diagnostic platform.
Sunnyvale, Calif.-based Pathwork originally submitted the TOO test to the FDA in January 2007, and the firm began offering it through its CLIA-certified laboratory in April of this year (see BAN 1/16/2007, 4/22/2008).
CEO Deborah Neff told BioArray News this week that the company now believes that it has the right instruments in place to formally market the test and to add diagnostic products in years to come.
One important factor behind the clearance is the firm’s relationship with the FDA, which evolved while the agency was simultaneously drafting its guidance on in vitro diagnostic multivariate index assays. Pathwork’s TOO test is the second IVDMIA to be cleared by the FDA, following the clearance last year of Agendia’s array-based MammaPrint test for breast cancer recurrence (see BAN 2/13/2007).
Neff described the IVDMIA clearance process as “complex” and said that Pathwork had to “do reproducibility studies and demonstrate that … our test continued to perform consistently across [all] variables.”
She described the FDA as “diligent” in its efforts to obtain confidence in the reliability of Pathwork’s test, and said that it had taken longer than expected to achieve clearance because “the technology is new, the approach is different, and it took a fair amount of work to go through process.”
Neff said she now believes that the avenues to clearance that were established during the review process will make it easier for Pathwork to obtain similar clearances in the future. “We expect our next clearance to be more straightforward because we are a predicate to ourselves,” Neff said. “We know what kind of data we need to present to the FDA and things like that, but I think the IVDMIA process will be complex until more of these kinds of tests come through this system.”
“I think the IVDMIA process will be complex until more of these kinds of tests come through this system.”
Pathwork is currently hiring and pursuing other opportunities, such as publishing papers in peer-reviewed journals and attending trade shows, to raise awareness of the TOO test. Neff said that Pathwork currently employs around 30 people, but by the end of the year the company will have added between 10 and 15 people, most of them to its commercial team.
“We are obviously building our sales team as well as our technical and application support,” she said. Neff added that Pathwork is busy meeting with pathology and oncology department heads around the US to familiarize them with the TOO test, has articles submitted for peer-reviewed journals, is attending trade shows, and has several clinical studies underway to add data to “reinforce the validity of the test.”
One of Pathwork’s potential rivals, should it expand beyond the US, is Agendia’s CE-Marked CupPrint test, offered through that firm’s lab in the Netherlands, which also uses a gene-expression signature to identify cancer of unknown primary in patients. Agendia, however, has said it has no plans to pursue 510(k) clearance for CupPrint in the US (see BAN 2/13/2007).
One obvious obstacle for Pathwork is that arrays are a relatively new technology. However, Neff said that the “idea that an array is a nice platform if you are looking at a lot of data is more accepted than it was a few years ago” and that the core challenge for. Pathwork and others is to show the market that the “clinical information that you can capture from arrays is highly robust.”
Besides its test, Pathwork will also have to market its Clinical Laboratory Improvement Act-concordant Pathwork Diagnostics Laboratory, where the TOO assay has been offered as a homebrew service for the past four months.
Neff said that a combination of factors inspired the company to begin offering the TOO as a lab-developed test ahead of receiving 510(k) clearance. The first came directly from a 545-sample, multi-site validation study of the test performed at labs at Stanford University, Virginia Commonwealth University School of Medicine, and others, that led to interest from physicians associated with the institutions.
“We started getting inquires about getting access to the test from [these] physicians,” said Neff. “We had a high level of confidence that we met all standards and we thought that this would be a great way to get the test out in the market.”
Another issue is that some institutions are wary of making capital investments to bring molecular diagnostics in-house. Pathwork’s service allows them to gauge what kind of demand would exist before they go out and buy the instrumentation to run the tests.
“They can get up to speed, see how much volume exists, and make sure they need to bring it in-house,” Neff said. “It allows lower-volume customers and allows us to sell direct clinical kit to labs that want to offer in their institutions. That way we get the broadest coverage in the market place.”
Affymetrix manufactures Pathwork’s Pathchip microarrays plus its reagent kits and, for its service, processes the firm’s patient tissue samples in its clinical services laboratory. Pathwork manages the patient sample, performs the analysis, provides a report to a pathologist for review, and reports the findings back to the clinician, Neff said.
For the cleared test, however, Pathwork sells the kit, including the Pathchip chip, directly to its customers and is responsible for clinical and technical support. The TOO service costs $3,750, and the kit is likely to cost half as much, Neff said.
According to Neff, Pathwork sees its diagnostic lab service as a “great channel to bring new products into the market, mostly because of the time it takes to go through the process at the FDA.” She said that the firm’s general plan is to make future tests available through its lab and then via a 510(k)-cleared kit.
In terms of new products, Pathwork’s first priority is to expand the scope of the TOO test, which currently accepts only frozen tissue samples, to also work with formalin-fixed, paraffin-embedded samples and fine-needle aspirates. Neff said that TOO for FFPE samples should be available by the end of the year, while TOO for fine-needle aspirates will likely be on the market by mid-2009.
Pathwork is also working on other tests to follow the TOO test, though the company has not discussed its diagnostic plans in detail. Neff said that Pathwork is focused on “three or four large areas of oncology that you might expect us to be working on,” and that by the end of 2009, it’s likely the company will have narrowed its focus to a particular test.
“The future tests are most likely to be gene-expression based tests in oncology,” she said. “They will use the core technology we’ve developed to measure large numbers of multiplex gene-expression data and be able to get highly accurate clinical results as the output.”