A Pathwork Diagnostics (Redwood City, California) test designed to help physicians reduce diagnostic uncertainty for tumors of uncertain origin guiding them to provide more specific cancer therapy has received strong validation in a large study.

"It hadn't been previously demonstrated with this degree of robustness," Pathwork CEO Deborah Neff told Medical Device Daily. "The reproducibility across multiple sites wasn't a surprise, but the fact that we added rigorous validation criteria, challenged it and then we got very consistent results regardless of where the test was done or who ran the test was the most significant part of the validation study."

This data, which validates the predefined 1,550-gene expression profile, was needed as Pathwork Diagnostics endeavors to launch the test, currently conducted only at its own facilities, in a kit to be launched during the second half of the year.

The study, Neff said, proved that "You can take a test like this and put it out to a lab used to handling somewhat complex tests and get good results. That's important as we move forward with this as a send-out test."

The Pathwork Tissue of Origin Test uses a microarray to measure the expression pattern, comprising more than 1,500 genes, in the uncertain tumor and compares it to expression patterns of a panel of 15 known tumor types, representing 60 morphologies overall to help determine the tumor's origin, covering 90% of all cancers.

When doctors are faced with a poorly differentiated, undifferentiated or metastatic tumor, this test uses the tumor's genomic information to identify the specific site of origin.

The test received FDA clearance about eight months ago with data that demonstrated 89% positive agreement (akin to sensitivity) with available diagnoses and 99% negative agreement (akin to specificity) (Medical Device Daily, Aug. 4, 2008).

In the current multicenter, blinded study, which appears in the Journal of Clinical Oncology, the test examined 547 frozen tumor specimens from patients diagnosed with one of the tumor types in the panel, all of which were either metastatic, poorly differentiated or undifferentiated. The test demonstrated 88% positive agreement (akin to sensitivity) and greater than 99% negative agreement (akin to specificity).

Because tissue samples are prepared in two ways, frozen or paraffin-embedded, the company has checked to see if the Tissue of Origin Test works equivalently with both types.

The JCO paper reported results for frozen tissue samples, but the company did a validation study with formalin-fixed, paraffin-embedded (FFPE) specimens that showed similar performance.

"Based on our ability to use our proprietary analytics, we were able to get virtually identical performance levels between frozen and FFPE tests," Neff said. "They require slightly different processing. Our experience to date is that it's much easier for clinicians and pathologist to have access to paraffin-embedded rather than frozen samples."

Shawn Becker, MD, Pathwork's vice president, marketing and reimbursement, pointed out that when the data were stratified between metastatic and poorly undifferentiated specimens, the performance was also equivalent.

"When clinicians think about the difficulty of specimens, they say it's easiest to identify primary tumors," Becker said. "We only looked at poorly, undifferentiated or metastatic tumors and it turned out that we could answer to them with the same performance between the two."

The Tissue of Origin Test is a new tool to guide clinicians in choosing a specific cancer therapy.

"From an oncologist's perspective, sometimes chemotherapy choices are very different and so it's really important to be sure," Becker said. "Standard pathology tests haven't narrowed it down. We offer objective and complementary data not available through any other technology to guide therapy."

As a sign of the company's growth and confidence in the Tissue of Origin Test, it has moved from Sunnyvale, California to a larger facility in Redwood City, California.

The company will manufacture the kits in house and sell them for $1,875, half the price it currently charges to provide the lab service. It uses PathChip, a gene expression array custom-designed for the company by Affymetrix (Santa Clara, Florida). PathChip was the first custom Affymetrix gene expression array to be cleared for diagnostic use (MDD, Aug. 4, 2008).

"The test is a good foundation and positions us for future test development," Neff said. "We're always looking to make enhancements, so we'll continue to flesh out this product family around Tissue of Origin. We will continue to add capabilities to this test, but we are also doing feasibility work on tests in other areas in oncology."

Pathwork has formed a small sales team and will focus on oncologists, pathologists and some surgical oncologists at large medical and cancer centers.

Founded in 2006 through an $11 million financing, Pathwork last year closed a $20 million financing led by Abingworth, which joins the existing investors participating in the round, including Prospect Venture Partners, Advent Venture Partners, Novus Ventures, Venrock and Versant Ventures (MDD, Sept. 5, 2008).