NEW YORK (GenomeWeb) – Having recently published a multi-center clinical validation study of its blood test for early detection of colorectal cancer, Swiss molecular diagnostics firm Novigenix is now looking to expand the market for the assay in its home country and throughout the rest of Europe over the next year.
Novigenix's assay, called Colox, is unique in that it combines a 29-gene host immune response panel with a pair of tumor-derived protein biomarkers to detect not only early-stage colorectal cancer, but also large adenomatous polyps that can be precursors to cancer.
"It's really to select the right patients that have developed or are developing [colorectal] cancer, and then to follow up with diagnostic colonoscopy," Nicolas Demierre, director of business development at Novigenix, told GenomeWeb this week. "It's replacing screening colonoscopy, but will never replace diagnostic colonoscopy."
However, "combining the host response for the early signal, and the tumor-derived markers that provide specificity … we really believe can be the gold standard for CRC detection," Demierre added. "This combination is unique, and it lets you detect polyps before the cancer even develops."
Early detection of colorectal cancer can be the difference between life and death. According to a 2009 colorectal cancer epidemiology survey, more than 90 percent of patients who are diagnosed when localized tumors are confined to the colon wall can survive with the help of surgery. However, if left untreated, the cancer will spread, reducing the survival rate to 70 percent. Once the cancer metastasizes, the survival rate is a bleak 10 percent.
The Colox test was originally developed by Swiss molecular diagnostics firm Diagnoplex, which was working on it as early as 2008. The host immune response portion of the test has morphed from a single-channel multiplexed PCR assay to a more conventional well-plate real-time PCR assay, but the 29 biomarkers that comprise the panel have remained unchanged throughout this evolution.
In 2014, Diagnoplex launched the assay with CE marking in its home country through Unilabs' clinical diagnostic service laboratories. In early 2015, Novigenix acquired Colox from Diagnoplex with the intent of disseminating it more broadly in Switzerland, throughout Europe, and eventually into other markets, such as North America.
The current iteration of the test, which can be run as a lab-developed assay or is provided in kit form by Novigenix, also includes two tumor-derived protein biomarkers, CEA and CYFRA21-2, which increase the assay's specificity for colorectal cancer. To perform the test, a technician extracts RNA from isolated cells in a patient's blood sample, loads them onto a well plate with the assay reagents, and performs singleplex PCR to measure expression of the 29 host response genes. Overall run time is approximately 4.5 hours.
Demierre said that the assay is validated on a Roche LightCycler platform but in theory could be run on other real-time PCR machines. Meantime, the company recommends using a Roche Cobas or Abbott Architect immunoanalyzer to detect the tumor protein biomarkers.
"That's very conventional," Demierre said. "We are talking to big labs, [which] have all the molecular diagnostic and molecular biology [instruments] in place. So we are talking to people that already have real-time PCR machines and protein analyzers, and that's pretty standard."
Late last month, researchers from Novigenix and several Swiss and South Korean hospitals and research institutes published a clinical validation of Colox in Clinical Cancer Research. In the study, which began in 2010 and wrapped up in 2013, the researchers analyzed blood samples from 1,665 subjects referred for colonoscopy or surgery at Swiss and South Korean hospitals. Of these, 782 were recruited in Switzerland and 623 in South Korea, and the recent publication focused only on the Swiss cohort, with the South Korean data to be presented later.
The study was also run in two stages: one to provide baseline sensitivity and specificity of the blood test, and one to prospectively validate Novigenix's "multi-gene, multi-classifier" algorithm for automatically scoring the 29-target gene expression panel.
Considered alone, the gene expression panel detected colorectal cancer and large adenomatous polyps with a sensitivity of 79.5 percent and 55.4 percent, respectively, with 90 percent specificity. Combining this panel with the two tumor-derived protein markers nudged specificity to 92.2 percent with slightly reduced sensitivities of 78.1 percent and 52.3 percent for colorectal cancer and large adenomatous polyps, respectively.
The authors of the study concluded that the test's performance "is consistent with its use as a [colorectal cancer] detection tool for average-risk individuals reluctant to undergo upfront colonoscopy," and that the "convenient and routine blood test can help identify individuals who will benefit most" from the invasive procedure.
The test's performance is on par with other assays for early colorectal cancer detection — most notably Exact Sciences' Cologuard and EpiGenomics' Epi ProColon, both of which have US Food and Drug Administration clearance (Epi ProColon just received clearance last month). Novigenix's tasks now include refining it to further boost sensitivity and specificity, and convincing physicians and payors in Switzerland and beyond that even with its current performance, Colox can be a useful tool in guiding patients to colonoscopy.
Demierre said that Colox has shown superior specificity compared to Cologuard and Epi ProColon, but the numbers don't quite bear that out. According to Exact Sciences' website, Cologuard is less specific, at 87 percent, but Epigenomics states that Epi ProColon has a specificity of 97 percent. Meanwhile, Colox and Epi ProColon have similar sensitivities, but Cologuard has a superior sensitivity of 92 percent for detecting cancer stages I through IV and 94 percent for detecting early-stage disease (stages I or II).
However, "if you look at the precursor stages — the polyps that can evolve and [become cancerous] — Colox is leveraging the host immune response, so as soon as you have a lesion occurring in the colon, you have a change in your gene expression profile and we can pick this up," Demierre said. "This really gives Colox … the best sensitivity and specificity [for polyps]."
Like in many countries, early detection of colorectal cancer in Switzerland has not been very state of the art, and as a result, Colox's sales in the country have been modest — in the thousands of patients have been tested since the assay was launched, Demierre said. But things are beginning to change: This year, two Swiss cantons are launching pilot screening programs, one of which is expected to recruit some 5,000 subjects.
Colox is currently not covered by insurance companies in Switzerland, so patients need to pay out of pocket. However, Novigenix is now beginning a prospective trial with many of the same collaborators as the recently published study to build the clinical evidence around the test and hopefully help it achieve reimbursement and broader availability.
To support this, the company has begun discussions with investors around a Series B financing round, the proceeds from which will also support expansion outside of Switzerland, Demierre said. He declined to disclose a target amount for the financing, but said that the company hopes to wrap it up late this year or early next year.
After that, a foray into the US market is a possibility, but, judging by the arduous and expensive roads that Exact Sciences and Epigenomics had to take to achieve regulatory clearance, Novigenix may need a commercial partner.
"We clearly appreciate the time and financial resources it takes to go through the FDA," Demierre said. "We are now really in the process of evaluating this. Epi ProColon just got FDA approval for the first blood test [for colorectal cancer detection], so it might really [be] a predicate for us [and] make the path through FDA a bit simpler."