Orion Genomics is hoping to be the first company to develop a diagnostic designed to help doctors identify patients in their 20s and 30s who are at increased risk for developing colorectal cancer later in life.
The company announced its intention to develop the test last week after signing a worldwide exclusive license with Johns Hopkins University for a biomarker that involves loss of genomic imprinting of the insulin-like growth factor 2 gene.
Orion’s risk-assessment test will aim to identify people who carry the IGF2 biomarker “and may be at increased risk of developing sporadic colorectal cancer,” the company said in a statement. “It is expected that the test will enable at-risk patients to undergo screening for colorectal cancer significantly earlier, allowing physicians to remove precancerous polyps and prevent future colon cancer.”
Orion said the license covers a suite of issued and pending JHU patents covering imprinting abnormalities of IGF2.
Currently, 85 percent of colorectal cancer cases occur in those with no known risk factors, a spokesperson for the company said. The American Cancer Society recommends annual digital rectal exams for individuals aged over 40; and fecal occult blood tests and sigmoidoscopy every three to five years for individuals aged 50 and older.
According to Orion CEO Nathan Lakey, the prototype of the CRC risk test is a SNP-based allele-specific expression assay that shows that imprinting of one of the alleles has been lost. The test “could potentially identify high-risk individuals at an earlier age who could benefit from undergoing colonoscopy screening 10 to 20 years earlier than currently recommended,” Orion said in a statement.
With the availability of this test, Lakey said Orion is hoping to enable doctors to “provide more targeted CRC monitoring and shift resources to those more likely to develop cancer.”
“Screening allows physicians to identify and remove precancerous polyps and prevent future colon cancer,” he added.
Lakey told Pharmacogenomics Reporter last week that the company intends to submit its CRC risk test for clearance by the US Food and Drug Administration in 2009, following the completion of a large prospective confirmatory trial.
JHU researchers are currently conducting a large multi-center prospective trial to study the link between the IGF2 biomarker and colorectal cancer in peripheral blood.
The trial involves samples from the Prostate, Lung, Colorectal and Ovarian Cancer study of more than 150,000 participants from multiple US centers. The PLCO study, sponsored by the National Cancer Institute, is in its 10th year.
“When used in conjunction with colonoscopy screening, our test has the potential to reduce colorectal cancer incidence as well as reduce associated colorectal cancer treatment costs in a US clinical market size of more than 81 million people.”
“If the resulting data are positive, and earlier retrospective studies are confirmed, these data will be used as the evidence basis for regulatory approval for the Orion colorectal cancer risk test worldwide,” Lakey told Pharmacogenomics Reporter.
Expecting to submit the test for regulatory approval next year, Orion intends to broadly market the CRC risk test to people in their 20s and 30s, a market of nearly 82 million in the US, and to primary-care physicians.
Lakey did not discuss how the company plans to educate this broad population about the test or the link between CRC risk and the IGF2 biomarker, saying it was too early to have a marketing discussion.
However, if confirmatory studies are successful in establishing the utility of IGF2 screening, then Orion's test could potentially alter the entire CRC screening market, according to a researcher involved in the studies underway.
“If the power of this risk marker shown in earlier clinical studies is confirmed by the large prospective trial now underway, it can potentially change the way populations are screened for colon cancer,” Graham Colditz, associate director of prevention and control at the Alvin J. Siteman Cancer Center, said in a statement issued by Orion.
“The test may identify people who should be screened earlier in life and more frequently, while also identifying individuals who can start screening later than what is now recommended, thus serving as a tool to help physicians in developing targeted monitoring plans and shifting resources to the people most likely to develop colon cancer,” Colditz added.
The loss of imprinting of IGF2 and its link to cancer was discovered in 1993 by a group of Johns Hopkins University researchers led by Andrew Feinberg. Since then, there have been nearly 80 peer-reviewed papers published on investigating the link.
According to Orion, studies have found that colorectal cancer and adenoma patients are at least five times more likely than cancer-free patients of the same age to carry the IGF2 biomarker.
Furthermore, studies have determined that around 40 percent of primary colorectal tumors have loss of imprinting of IGF2. The non-heritable epigenetic mutation is found in 7 percent to 10 percent of the general population.
The American Cancer Society estimates that in 2008, there will be approximately 108,070 new cases of colon cancer and 40,740 new cases of rectal cancer among men and women in the US. The risk of developing CRC is slightly higher in men than in women.
The disease, according to the ACS, is expected to cause nearly 50,000 deaths in the US, making it the second leading cause of cancer-related death when the death rates among men and women are considered together. However, the ACS attributes the 20-year decline in CRC-related deaths to earlier screening, which leads to the removal of polyps before they can develop into malignant tumors.
“We believe our risk assessment test will be easily incorporated into the routine management of colorectal cancer,” Lakey said in a statement. “When used in conjunction with colonoscopy screening, our test has the potential to reduce colorectal cancer incidence as well as reduce associated colorectal cancer treatment costs in a US clinical market size of more than 81 million people.”