By Ben Butkus
Epigenomics said this week that it has completed a key clinical trial for its real-time PCR-based lung cancer reflex diagnostic test, clearing the way for the test to receive the CE Mark for in vitro diagnostics and for the company to launch the test in Europe.
Epigenomics' test, the Epi proLung BL reflex assay, will be the company's second real-time PCR-based diagnostic test to receive the CE Mark for IVD. In October, the company launched the Epi proColon blood-based test for early detection of colorectal cancer.
In April, Epigenomics said that it had inked a deal with European clinical laboratory network Synlab to distribute Epi proColon (PCR Insider, 4/8/10). The company is similarly looking for a distribution partner in Europe as it prepares to launch Epi proLung, likely within a "few weeks," Achim Plum, senior vice president of corporate development for Epigenomics, told PCR Insider this week.
Epi proLung determines the methylation status of the SHOX2 gene in bronchial lavage material routinely obtained during the clinical workup of patients suspected to have lung cancer. Increased methylation of SHOX2 indicates the presence of malignant lung disease, according to multiple previous studies by Epigenomics and others.
Epi proLung detects SHOX2 methylation status, just as the Epi proColon test determines the methylation of the Septin9 gene in colon and rectal tumors, using a plate-based real-time PCR system, Plum said.
The Epi proLung test thus far has been validated for use on Life Technologies' Applied Biosystems 7500 Fast Real-Time PCR system, primarily because "it is more commonly found in the molecular pathology setting," Plum said. "However, we can easily validate it for use on another system, if necessary." To wit, the company originally released Epi ProColon for use on Roche's LightCycler 480 platform, then validated the test on the ABI 7500 Fast when it signed its distribution deal with Synlab.
The procedure for performing the Epi proColon and Epi proLung is "in principle the same," except for the fact that bronchial lavages produce much more "robust samples that have quite a lot of DNA," Plum said. Consequently, sample preparation for Epi proLung is much less involved than it is for Epi proColon.
"It's a one-day procedure" involving fractionation of cells from a bronchial lavage followed by DNA extraction and real-time PCR detection of target, Plum said. In addition, because the lavage usually contains plentiful DNA, there is no need to take an additional sample from a patient.
"You can use leftover material from cytology," Plum said. "If the pathologist decides to do our test, he can just use material from the cytology sample."
Epigenomics is betting that many European cytopathology labs will do just that. Traditional cytological analysis of suspected lung tumors produces a result only about half of the time, Plum said.
Meantime, Epigenomics demonstrated that its test can provide an answer in most cases where cytology fails. In a trial conducted at the University of Liverpool Cancer Research Centre in the UK, researchers John Field and colleagues used the Epi proLung BL reflex assay to determine SHOX2 methylation status in routinely obtained bronchial lavage of patients with confirmed bronchial carcinoma and patients with no evidence of malignant lung disease but who had other lung diseases at the time of bronchoscopy and a minimum lung cancer-free survival of 18 months.
In the study, the Epi proColon test correctly identified 81 percent of lung cancer cases with a 5 percent false positive rate, translating to a specificity of 95 percent, Epigenomics said. Results from the study have been submitted for publication in a peer-reviewed journal, Plum said.
Meantime, Plum said that the clinical study has demonstrated that Epi proLung fulfills the requirements for intended use as an aid in diagnosing lung cancer, and obtaining a CE Mark for IVD for epi proLung is now "just a matter of documentation that needs to be done. The intended use is to aid in diagnosis [of lung cancer], and there is more than enough evidence now to support that use."
Plum added that Epigenomics plans to launch Epi proLung within a "few weeks," and that its first focus is on establishing the test in "leading pathology centers in German-speaking countries."
Epigenomics, which is based in Berlin and has a US subsidiary in Seattle, has previously pursued a dual strategy for its DNA methylation tests that consists of selling the test itself or through a distributor, as well as licensing its methylation biomarkers to partners to use in development of their own tests.
Its diagnostic partners to this point have included Abbott, Sysmex, Quest Diagnostics, ARUP Laboratories, and Warnex. However, the company has not yet partnered with anyone for the SHOX2 biomarker, Plum said.
"We may look into partnering on sale and marketing of the product, but we haven't licensed the biomarker yet," he said. "For now we are looking for a distributor in Europe."