By Ben Butkus
ARUP Laboratories this week launched a laboratory-developed, blood-based PCR test for colorectal cancer based on Epigenomics' Septin9 biomarker, joining Quest diagnostics as the only US provider of a single-biomarker blood test for the disease.
According to ARUP, the test, which amplifies and detects methylated Septin9 DNA from patient plasma samples, has been shown to identify a higher proportion of colorectal cancers than other Septin9-based tests, such as Quest's US test, called ColoVantage; as well as similar CE-marked in vitro offered in Europe by Epigenomics and Abbott.
Previous studies of the Septin9 biomarker from Epigenomics have demonstrated a clinical sensitivity of 70 percent with 89 percent specificity, numbers also cited by Quest on its web page for the ColoVantage test.
Meantime, ARUP's test is "routinely getting 90 percent sensitivity at 89 percent specificity," Karen Heichman, vice president of product development at ARUP, told PCR Insider this week. "Basically we ended up getting a much improved sensitivity."
Heichman said that ARUP's test is an optimized version of a protocol previously described in a publication by Epigenomics scientists, but she was reluctant to provide specific details of the improvements that helped achieve the greater sensitivity.
"It's just the basic kind of stuff you do when optimizing PCR," Hiechman said. "All the different components that go in to a reaction – we were able to play around with those a bit."
The kits used by ARUP for extracting DNA from plasma and from bisulfite-treated DNA "are basically commercially available kits," Heichman said. "We really optimized the PCR detection step in house, and spent quite a bit of time on that. That was one of the key components that led us to have increased sensitivity."
ARUP runs its test on the Roche LightCycler 480, although Heichman noted that "there is really nothing special about that platform" and that ARUP may eventually adapt the test for another PCR instrument.
ARUP's test, like others based on Septin9 methylation, is not meant to replace colonoscopy, still considered to be the gold standard, according to Heichman.
Nevertheless, "half of Americans age 50 and over are not getting any kind of screening [for colorectal cancer] at all," she said. "About 40 percent of Americans follow the guidelines and get a colonoscopy; and then maybe between 5 and 10 percent follow guidelines for stool-based screening. But that is not very popular, as you might imagine."
The idea behind the ARUP test, Heichman said, is to offer "a simple blood test where you could draw the specimen in the doctor's office when you're … getting your cholesterol screening and such. We're trying to get those people that for one reason or another don't get screened," since patients with stage I or II colorectal cancer are much less expensive to treat and have much better outcomes than those whose disease is not detected until much later.
Meanwhile, the availability and improved performance of the new test is considered by Epigenomics to be a boon as the company pursues its dual business strategy of direct commercialization and non-exclusive licensing of its biomarkers to independent test developers to create molecular diagnostics.
"The test performance demonstrated by ARUP in the clinical validation of their laboratory-developed test … underscores the full potential this biomarker has," Epigenomics CEO Geert Nygaard said in a statement.
"As a single biomarker test it compares very favorably in terms of its clinical performance and economics to competing approaches," which may require a handful of biomarkers to be tested from stool samples or as many as 200 biomarkers from blood to be analyzed on an array-based system, Nygaard added.
ARUP, which is a national reference laboratory run by the University of Utah, non-exclusively licensed the Septin9 biomarker from Epigenomics in August 2009. Besides receiving an undisclosed up-front payment and royalties on test sales, Epigenomics sees in ARUP "an attractive partner in that they are very … medical community- and science community-based," Achim Plum, vice president of corporate development for Epigenomics, told PCR Insider this week.
"They have very strong interactions with the academic environment – not just the University of Utah, but in general," Plum added. "And their positioning as a very science-driven, innovation-driven laboratory … helps us establish this new testing modality in the market."
Other licensees of Septin9 include Quest, which launched its ColoVantage test earlier this year; Abbott, which, like Epigenomics, has launched a CE-Marked IVD based on the marker in Europe and the Asia/Pacific region; and Canada's Warnex Laboratories, which plans to introduce a laboratory-developed test later this year.
Canadian company GeneNews also has a blood-based test for colorectal cancer called ColonSentry, which uses qRT-PCR to quantify a panel of seven mRNA biomarkers that are differentially expressed in whole blood taken from CRC patients compared with controls. ColonSentry is available in Canada but not in the US.
Plum said that Epigenomics has "a limited number of further global licensing slots on the IVD side of things. On top of that in the US and some other regions … where it is harder to get an IVD to the market because the regulatory hurdles are higher … we offer non-exclusive licenses to do laboratory-developed tests."
In the US, Epigenomics and Abbott are separately pursuing IVD approval from the US Food and Drug Administration.
Epigenomics' CE-Marked IVD test is currently run on PCR platforms that also have the CE Mark, but do not have IVD clearance in the US, such as the LC 480 and Life Technologies' Applied Biosystems 7500 Fast Real-Time PCR system.
"That doesn't work in the US, so there we have to put it on an FDA-cleared device, which is why we need a little bit more time than Abbott," which is developing its test for the RealTime system m2000, Plum said. The m2000 received 510(k) clearance from the FDA earlier this month.
Epigenomics has been in discussions with companies that offer PCR platforms that have either achieved 510(k) clearance or are in development to do so, although Plum declined to identify any potential partners. "We haven't totally nailed down yet what our system looks like," he said. "In diagnostics, a lot of differentiation happens via the instrument on which the test is run."
Plum also noted that various IVD tests would complement each other more than they would compete with each other; and that prior widespread adoption of laboratory-developed tests that use Septin9 can only help the cause of Epigenomics, Abbott, or any other developers of IVD tests for the US market.
"We realize in the US that there is a chance to give out ... licenses, and that way our partners are present already with Septin9 testing on the market, even prior to a full-blown FDA-approved IVD test kit," Plum said. "So that's the strategy behind it. And we look for high-quality laboratory partners that can do it."