DNA methylation diagnostic developer Epigenomics is closer to launching a blood-based lung cancer screening test that it hopes will improve early detection of the disease.
In a recent study, the company pinpointed a methylation biomarker that can be detected in the blood plasma of lung cancer patients and possibly be developed as a screening test for the disease.
Epigenomics is planning to unveil the identity of the specific biomarker when it publishes data from the study in scientific publications, Vice President of Corporate Communications Achim Plum told Pharmacogenomics Reporter this week.
The fact that this proprietary biomarker can be detected in blood plasma of lung cancer patients is an “important prerequisite for developing a convenient blood-based early detection test for this cancer,” the company explained in a press release. “The study came to the result that the most promising candidate biomarker detects patients with lung cancer, and differentiates them from individuals with positive computer tomography due to non-cancerous lung diseases.”
Epigenomics would not comment on which diagnostics partners it plans to develop the test with or when the lung cancer screening test may be launched. For now, the company is focused on planning additional studies to test the feasibility of developing a test with this initial data.
Epigenomics analyzed two DNA methylation biomarkers, a novel biomarker the company discovered and the control biomarker RASSF1A, in 100 patients with either lung cancer or benign lung disease. The novel proprietary biomarker demonstrated 69 percent sensitivity and 91 percent specificity in discriminating patients with non-small cell lung cancer from those with non-cancerous lung diseases in blood plasma.
“This means that no more than 9 percent false positive test results occurred and 69 percent of the non-small cell lung cancer patients were found through a simple blood test,” Epigenomics said in a release. “Based on this proprietary novel DNA methylation biomarker and the encouraging results, Epigenomics will continue the development of its lung cancer screening test.”
The study, conducted in partnership with the Department of Pneumology at the Charité in Berlin, took less than one year from discovering the novel lung cancer biomarkers to clinical proof of concept, the company said.
Epigenomics identified its proprietary biomarker for the lung cancer test as part of a study conducted last year to discover DNA methylation-based specific lung cancer markers. In that study, Epigenomics compared lung cancer tissue with normal lung tissue with its Differential Methylation Hybridization technology, which measured the methylation status of 50,000 genomic fragments on a microarray. This study yielded a number of genes that are hypermethylated in lung cancer, and the company filed patents for these markers. The lead biomarker Epigenomics is using for the lung cancer test was among this set of markers.
Although Epigenomics is not yet naming the proprietary biomarker, the company did reveal that it performed statistically significantly better than the control RASSF1A in the clinical trial. According to Epigenomics, the biomarker’s superiority over “one of the best described lung cancer DNA methylation biomarkers in the scientific literature,” supports its potential utility for a lung cancer test.
Plum described the marker as a gene frequently hypermethylated in lung cancer, but rarely in normal tissue, which makes it a suitable candidate for developing a screening test in this disease population.
"As tumors shed DNA to the blood stream, the presence of methylated DNA of this gene in blood plasma indicates the presence of lung cancer," Plum explained, adding that for this reason, the biomarker is specific to lung cancer and is not being used in other indications.
"In the recent study we could detect it in the blood plasma of the majority of the NSCLC cases studied but rarely in the critical controls, [or in patients with] benign lung diseases, that were tested," Plum said. "This indicates that when using this lead biomarker, potentially combined with complementary markers, we may be able to develop a convenient blood-based lung cancer early-detection test that is very sensitive and very specific."
According to Plum, the company will perform additional clinical studies to demonstrate the feasibility of this concept. The company would not comment on potential development partners for the lung cancer screening test.
When conducting the clinical research study, Epigenomics used a proprietary real-time PCR technology variant called HeavyMethyl to detect the DNA methylation biomarker. "But we can transfer our biomarker assays [to] a variety of molecular diagnostics platforms that use other technologies," Plum said.
The National Cancer Institute estimates that in 2007, there will be 213,380 new cases and 160,390 deaths from lung cancer in the US. Most patients are diagnosed with the disease in advanced stages when symptoms appear. Only 16 percent of lung cancers are diagnosed at an early stage and as a result, approximately 90 percent of patients die of lung cancer within two years, Epigenomics said.
“This indicates that when using this lead biomarker, potentially combined with complementary markers, we may be able to develop a convenient blood-based lung cancer early detection test that is very sensitive and very specific.”
“Currently no such test is available for mass screening, especially for the high-risk group of more than 90 million smokers in the major markets. We aim at developing such a test and have now made substantial progress to this end,” said Epigenomics Chief Operating Officer Christian Piepenbrock in a statement. “In the next step, we will further improve the performance of the test based on our newly identified biomarker and potentially other complementary biomarkers.”
The company is hoping that its screening test will be particularly beneficial for detecting cancer in people at high risk of developing the disease.
Considering the high-risk population of 90 million smokers, Epigenomics estimates the total global sales potential for a lung cancer screening test could be as much as €800 million ($1.1 billion) for IVD companies. The market potential for a lung cancer screening test could be as much as €2 billion ($2.7 billion) factoring in the general population aged 45 or older, the company said.
Epigenomics is also developing other diagnostic screening tests for the early detection of prostate, colorectal, and lung cancer. The company has a validated biomarker panel for the colorectal cancer test and proprietary DNA methylation markers for prostate and lung cancer screening.
The company’s global marketing and commercialization strategy for its early cancer detection tests includes an initial launch as a testing service in US reference laboratories, followed by a CE-marked test kit in Europe, and ultimately an FDA-approved test kit in the US. If the company commercializes a lung cancer screening test, it will likely follow a similar strategy.
"For the IVD test kit development and commercialization we pursue a non-exclusive partnering strategy with diagnostics industry players," Plum said. "We currently do not give any guidance on when our lung cancer test may be launched."
Plum said that the company is currently in discussions with potential diagnostic partners regarding its colorectal cancer test, which is “more advanced in development” than its other tests.
The company has a specialty diagnostics franchise for high-risk cancer patients, which includes a surveillance test for colorectal cancer biomarkers, and a tissue-based prognostic classification test developed with Qiagen and Affymetrix for prostate cancer.
Epigenomics said that the colorectal and prostate diagnostics are slated for launch as homebrew tests in 2008.