By Tony Fong
Following successful pre-clinical trials performed last year, EDP Biotech is preparing to submit its colorectal cancer diagnostic for regulatory approval with the US Food and Drug Administration.
The company plans to meet with the agency before the end of the first quarter to discuss the test, called ColoMarker, and then to begin a clinical trial in the hopes of getting FDA clearance in about three years, Kevin Jones, the company's chief scientific officer, told ProteoMonitor this week.
In the meantime, EDP Biotech has started discussions with other firms about possibly partnering on commercializing the test as well as setting reimbursement rates for it. If the company is successful in bringing ColoMarker to market, it would be the first commercial launch by the four-year-old shop.
ColoMarker is based on a single protein, CA11-19.
EDP, based in Knoxville, Tenn., was formed when it bought the assets of two other local diagnostic-development firms, JCL and Concepto. As part of the purchases, EDP acquired both a product and technology portfolio, including biomarkers for various indications from JCL.
Eventually EDP decided to discontinue JCL and Concepto's product lines, and instead, concentrate on developing a biomarker business.
In particular, EDP and its advisors zeroed in on CA11-19, a glycoprotein, as a biomarker with clinical potential. JCL had originally discovered and isolated CA11-19 in cancer tissue about 20 years ago, but because of questions over the purity of the biomarker and the quality of the work leading up to its discovery, it had "languished, not going anywhere," Jones said.
While CA11-19 was discovered and investigated as a general cancer marker without "any particular target," data from JCL's research also indicated that it might have use for the detection of colon cancer, Jones said. As a result, during the next few years EDP's research was directed at determining its performance as a marker for the disease
Last year, the company conducted two studies that tested the biomarker's clinical efficacy. In the first test, which investigated about 2,000 samples, researchers found that CA11-19 is a common protein found in everyone.
But in some samples, levels of CA11-19 spiked, leading EDP to believe that its overexpression corresponded with colon cancer.
In a follow-up study of 400 at-risk patients who had been referred to gastroenterologists because they had shown potential symptoms of the disease, "the results that we got were absolutely mind-blowing," Jones said. "Every sample from a patient with early stage 1 through 3 colon cancer came back with" overexpressed CA11-19.
According to EDP, ColoMarker had greater than 99-percent accuracy based on the two pre-clinical trials. The test has shown "incredible accuracy to detect early-stage colon cancer," Jones said, adding that EDP's goal is to develop the test as a general screen to detect "practically all of stage 1, 2, or 3 colon cancer."
Current methods for diagnosing the disease usually start with a physical exam to detect a mass that may be indicative of disease. It can then progress to a fecal occult blood test, sigmoidoscopy and/or colonoscopy.
The advantage of Colomarker — aside from its accuracy — is that it is blood based and therefore relatively simple and inexpensive to extract a sample and perform the test, Jones said.
"It's a sandwich immunoassay, which means it can be put on any existing technology so you don't need to buy new systems … to run it," Jones said. "It's a simple, standard technology which can be widely accessed, widely used."
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While colonoscopies are the gold standard of screening tests for colon cancer, only about 18 percent of Americans aged over 50 — the American Cancer Society's screening threshold — actually get a colonoscopy, Jones said, citing ACS figures.
Among the common complaints of a colonoscopy is that the pre-procedure preparation is uncomfortable while the test itself is invasive. The test is also costly, ranging between $1,500 and $5,000.
The National Cancer Institute says that approximately 106,000 new cases of colon cancer were diagnosed in 2009 and about 50,000 deaths occurred last year from colon and rectal cancers combined.
The hope is that making a test that is more consumer-friendly will lead to more patients being tested, which will ultimately help identify the disease earlier, when chances of successful treatment are significantly improved. A patient who has colon cancer detected in stage 1 has a better than 90 percent chance of surviving beyond five years, while at stage 4, the survival rate drops to less than 10 percent, Jones said.
He said that EDP does not see ColoMarker and colonoscopies as competitors. The idea is that when a patient goes for a physical, ColoMarker would be given as an initial screen. If levels of CA11-19 are elevated, the doctor and the patient would then consider whether more testing should be done.
"Our aim would be to run this as a general screen so that doctors can have another piece of information to help them talk to patients about the risk factors that they have and whether they should be going in for a colonoscopy," Jones said.
EDP doesn't yet have the data necessary to pursue ColoMarker as a general screen for colorectal cancer, Jones acknowledged, but based on preliminary results, "there appears to be a good correlation between elevated levels of this biomarker and colon cancer."
The company has not yet decided whether it will submit ColoMarker for 510(k) notification or for pre-market approval. 510(k) is for devices that are substantially "equivalent to a predicate," which means there is already a device on the market that is considered to have minimal risk to patients. The PMA process is for devices that have the highest risk.
The initial target market for the test is the over-50 age group, but could be extended to include a younger population with a family history of polyps and gastrointestinal cancers, Jones said.
The company filed a patent application covering CA11-19 in October 2009. The next step is to meet with the FDA, "to work out what our claims can be," design a clinical trial accordingly, and get the trial begun by the end of the first quarter. EDP has been in discussions with "four or five" centers who could potentially collaborate with EDP on a clinical trial, though Jones declined to identify them.
While the company has done "some investigation looking at a multivariate assay," for now it is concentrating developing ColoMarker as a single marker based on CA11-19, Jones said.
"At this point we're focusing on what we have to get this marker through the FDA. Until we get this marker validated, there's no chance of taking it to a multivariate" assay, Jones said.
In addition to CA11-19, EDP is developing a protein biomarker, early conception factor, or ECF, to detect conception. In human applications, any test using ECF would have use in an in vitro fertilization setting. Such a test would be able to tell within a few hours whether conception has occurred. It would not be used as a general pregnancy test.
The other market for an ECF-based diagnostic is in animal husbandry where the test could give much faster results than other methods such as palpitation and ultrasound, Jones said.