Epigenomics has licensed its DNA-methylation biomarker Septin 9 to Quest Diagnostics, which the company will use to develop a homebrew colorectal cancer diagnostic.
Quest is the first commercial laboratory in the US to obtain a non-exclusive license to the Septin 9 biomarker from Epigenomics for the manufacture of a laboratory-developed colorectal cancer test. Epigenomics granted Quest exclusivity for an undisclosed period for being a “first-mover” in the US, in exchange for upfront and milestone payments, as well as royalties on sales of the test.
Epigenomics’ deal with Quest comes five months after Epigenomics licensed the marker to Abbott, which will use it to develop a Septin 9-based in vitro diagnostic kit. However, this kit will take some time to come to market, since it will require regulatory approval from the US Food and Drug Administration and CE mark in Europe. Abbott will likely launch the test kit in Europe in 2009 and in the US in 2010.
Quest plans to develop the Septin 9 DNA-methylation test, which could be available in the US as early as this year, as a supplement to conventional methods of colorectal cancer screening, including colonoscopy and fecal occult blood tests.
However, currently, many patients refuse to undergo colonoscopy because of its cost or its invasiveness. Since the diagnostic test will be blood-based, it has the potential to improve compliance — “the major problem with current screening,” an Epigenomics spokesperson told Pharmacogenomics Reporter this week.
In 2007, colorectal cancer caused 52,000 deaths in the US. However, if the disease is detected early, patients have a 90 percent chance of surviving for at least five years.
The American Cancer Society recommends that all men and women at 50 years or older with an “average risk” of developing the disease should be screened regularly. However, a recent study cited by Epigenomics found that only about one in four patients receiving Medicare received guideline-based follow-up screening between 1998 and 2004.
In clinical trials, Epigenomics has demonstrated that methylated DNA of the Septin 9 gene in blood plasma can help gauge the presence of asymptomatic, early-stage colorectal cancer. By encoding a protein involved in cell division, Septin 9 is thought to play a role in oncogenesis.
Once the Septin 9 test becomes commercially available, the company and its development partners will lobby patient groups and professional cancer societies to include the test in their colorectal cancer treatment guidelines.
In multiple clinical trials with about 3,000 blood plasma samples from colorectal cancer patients, healthy controls, and individuals with non-cancerous colon diseases, plasma levels of methylated DNA of Septin 9 shed by tumors was shown to accurately predict early-stage colorectal cancer.
In one 2006 study, for example, Epigenomics showed that methylated Septin 9 DNA as a biomarker in blood plasma could detect early-stage colorectal cancer with as much as a 90 percent specificity and a 70 percent sensitivity when the test is tuned for “high sensitivity.”
The Epigenomics spokesperson cited another independent study in more than 7,000 normal and tumor tissues, which indicated “there is consistent overexpression of Septin 9 isoforms in a number of tumor tissues.”
The findings showed that Septin 9 “is likely a type II cancer gene where changes in RNA transcript processing control regulation of different protein products, and the levels of these altered protein isoforms may provide answers to the gene's role in malignancy.”
The spokesperson added that in tissue studies of colorectal cancer, “certain regions of the Septin 9 [gene] are highly methylated in more than 90 percent of colorectal cancer tissues but not in control tissues.”
Epigenomics is particularly focused on using DNA methylation to find biomarkers for disease diagnosis. In addition to biomarkers for colorectal cancer, the company is developing DNA methylation biomarkers for prostate and lung cancer.
Thus, given Quest's experience in DNA methylation diagnostics — it currently markets such tests for Prader-Willi and Angelman syndromes — the US-based reference lab could be a strong partner for Epigenomics for colorectal cancer.
In its biomarker research, Epigenomics used its proprietary HeavyMethyl technology, a real-time PCR method, to detect methylated Septin 9 DNA in plasma. Although Quest is entirely responsible for determining the platform for the test, it is likely the company will also base its homebrew diagnostic on real-time PCR.
While the price of the test will be “at the discretion of our partners who will market the test,” in Epigenomics' models, the company estimates that the colorectal cancer tests will cost patients between $100 and $150, the Epigenomics spokesperson said.
Once a lab-developed Septin 9 test becomes commercially available, Epigenomics and its development partners will lobby patient groups and professional cancer societies to include the test in colorectal cancer treatment guidelines, the spokesperson added. To that end, Epigenomics recently developed a medical advisory board comprising primary care physicians and gastroenterologists with expertise in colonoscopy, colorectal cancer screening, evidence-based medicine, outcomes research, and health-economic analysis.
Additionally, Epigenomics this year plans to start a large clinical cohort study comprising several thousand individuals. “With the data from that trial we want to demonstrate the health economic benefit of our test, which will be key to guideline inclusion and reimbursement,” the spokesperson said.