- Clinical study with patient cohorts from multiple clinical centers
completed
- All study endpoints met
- PITX2 biomarker classifies patients into groups at high and low
risk for relapse
BERLIN and SEATTLE, Oct. 16, 2008 (GLOBE NEWSWIRE) -- Epigenomics AG (Frankfurt:ECX) (Prime Standard), a cancer molecular diagnostics company developing tests based on DNA methylation, today reported positive final results from its prognostic prostate cancer study.
"After testing all patient samples for methylation in the PITX2 gene we have successfully conducted our final analysis," commented Dr. Gunter Weiss, Vice President Product Development at Epigenomics. "This analysis shows that PITX2 gene methylation is indeed a strong, independent prognostic marker that can help guide physicians to determine a patient's risk for relapse. The analysis demonstrated statistical significance for all study endpoints," Dr. Weiss added.
The clinical study successfully analyzed paraffin embedded tissue samples from 476 prostate cancer patients collected at four major clinical centers in Europe and the USA who had undergone radical prostatectomy, with the objective of validating the prognostic utility of Epigenomics' proprietary biomarker, PITX2. The primary endpoint of the study was to evaluate the methylation status of the PITX2 gene as an independent prognostic biomarker indicative of the risk of prostate cancer biochemical recurrence in patients following removal of the entire prostate, known as radical prostatectomy. This primary endpoint of the study was met by the statistically significant demonstration that patients with elevated PITX2 gene methylation level had a threefold higher risk of relapse following prostatectomy compared to patients with low PITX2 methylation (hazard ratio 3.0; p less than 0.00005).
As secondary endpoints, the study also analyzed whether measurement of PITX2 methylation adds clinical information to established prognostic parameters such as age, Gleason Score, tumor staging, pre-surgical PSA levels and surgical margin status. In each of the pair wise comparisons of PITX2 with one of these established parameters, high PITX2 gene methylation was an independent prognostic factor indicating more than double the risk compared to patients with low PITX2 gene methylation (hazard ratios greater than 2.3; p less than 0.0001). In the group of patients with an intermediate Gleason Score of 7, which present difficult decisions for doctors and patients due to difficulty in determining their prognosis, the PITX2 marker was able to discriminate patients into those with a high and low risk of disease recurrence (hazard ratio 2.0; p=0.005). PITX2 gene methylation remained a statistically significant independent prognostic factor even when it was combined with several established parameters (hazard ratio 1.9; p=0.004) demonstrating its added value in guiding patient management.
The study confirmed the clinical utility of the PITX2 biomarker for prostate cancer prognosis, first established in a 2006 clinical study on 605 prostatectomy tissue samples using real time PCR. In the current study the PITX2 gene methylation was measured reliably using an Affymetrix GeneChip(TM) platform, confirming the robustness of the marker across various assay technologies suitable for routine laboratory use.
Epigenomics has designed and analyzed the study together with its clinical collaborators at Baylor College of Medicine, Houston, Texas, USA, at Erasmus Medical Center, Rotterdam, The Netherlands, at Duke University Medical Center and the VA Medical Center at Durham, North Carolina, USA, and University Hospital Erlangen, Erlangen, Germany. A Publication of the clinical study data is planned in a peer-reviewed journal in due course.
"This test has appeared to add valuable prognostic information in every patient group in which it has been used," commented Stephen J. Freedland, MD, Staff Physician at the Durham VA and Associate Professor of Urology and Pathology in the Duke Prostate Center, Duke University Medical Center. "As an in vitro diagnostic test, this could be another important tool for patients who are seeking additional prognostic information beyond what is currently available," he continued.
"The prognostic information provided for patients at intermediate or high risk is especially remarkable," emphasized Prof. Thomas Wheeler, MD, Chair of the Department of Pathology at the Baylor College of Medicine. "Especially, this large group of patients should profit from the results of the tests."
"These are very good results based on rigorous study design and high quality data," explained Prof. Dr. Chris Bangma, Chairman of the Department of Urology at the ERASMUS Medical Center. "The reliability of the PCMCT assay is very remarkable and provides the basis for routine laboratory use," he added. This notion was confirmed by Prof. Dr. Arndt Hartmann, Director of the Institute of Pathology at the University Hospital in Erlangen who stated: "Technically, this has been a perfect study. For all but a single patient a valid PITX2 measurement has been provided. The technology is mature and ready for release."
Following these highly successful results of its clinical study Epigenomics intends to make the PITX2 assay available to clinicians and patients as soon as possible and is exploring several opportunities to commercialize PITX2. The marker has additional potential applications beyond prostate cancer prognosis, such as in breast cancer. Commercial options include licensing the biomarker and a suitable assay technology to reference laboratories, the launch of RUO products for clinical research in Europe, and potentially the transfer of the fully developed assay system to suitable partners for regulatory submission and commercialization as an IVD product. About Epigenomics' Prostate Cancer Molecular Classification Test
Prostate cancer is the most common cancer in American and European men. With an annual incidence of approximately 470,000 cases in the US and Europe, one in six men will be diagnosed with prostate cancer in his lifetime and about 100,000 men will die from the disease every year. Surgical removal of the prostate (radical prostatectomy) is performed as potentially curative treatment in about 40% of patients diagnosed with prostate cancer. Nevertheless, the disease recurs in about one in seven prostatectomy patients. However, the difficulty clinicians have is that even with the use of current prognostic parameters, there still remains considerable uncertainty concerning which patients will eventually relapse. Epigenomics is developing a prostate cancer molecular classification test based on the DNA methylation biomarker PITX2 that will provide physicians and patients with prognostic information on disease recurrence by identifying those prostatectomy patients at increased risk. Currently, prognostic information is mainly derived from clinical and histopathological parameters, such as tumor size, Gleason Score and pre-surgery PSA levels. In a study published at the 2006 annual AACR meeting, Epigenomics has shown that DNA methylation of PITX2 constitutes a strong prognostic marker for outcome prediction after radical prostatectomy. In this study, PITX2 separated post-prostatectomy cancer patients into two distinct groups: Those with a high likelihood of cancer recurrence and those with a low likelihood of cancer recurrence. Furthermore, PITX2 methylation added significant information to established clinical parameters. Remarkably, the PITX2 biomarker was able to predict outcome in patients diagnosed with Gleason 7, for which reliable prognosis based on conventional parameters is particularly difficult. These findings were now confirmed with the study published today. The demand among physicians for such a molecular diagnostic test is high, since it identifies patients with a poor prognosis that are possibly under-treated.
About Epigenomics AG
Epigenomics is a molecular diagnostics company with a focus on the development of novel products for cancer. Using DNA methylation biomarkers, Epigenomics' tests in development aim at diagnosing cancer at an early stage before symptoms occur and thereby may reduce mortality from this dreaded disease.
Epigenomics' product pipeline contains a validated biomarker for the early detection of colorectal cancer in blood plasma, and further proprietary DNA methylation biomarkers at various stages of development for prostate and lung cancer detection in urine, blood and bronchial lavage specimens. Epigenomics' biomarker Septin 9 for the early detection of colorectal cancer in a simple blood sample demonstrated continuously highest performance in multiple clinical studies with in total more than 3,500 individuals tested.
For development and global commercialization as in vitro diagnostic test kits, Epigenomics pursues a non-exclusive partnering strategy with diagnostics industry companies. As a first strategic partner, Abbott Molecular Inc. licensed the worldwide non-exclusive IVD rights to Epigenomics' proprietary Septin 9 biomarker for colorectal cancer. Epigenomics also aims at giving patients and doctors early access to these biomarkers through reference laboratory testing services. As a first reference laboratory partner, Quest Diagnostics Inc., the leading provider of diagnostic testing, information and services, obtained the license to commercialize a laboratory-developed test (LDT) for Septin 9 in the U.S.
Partners in the health care industry and the biomedical research community can access Epigenomics' portfolio of proprietary DNA methylation technologies and biomarkers protected by more than 150 patent families through research products, Biomarker Services, IVD Development Collaborations, and Licensing. The company is headquartered in Berlin, Germany, and has a wholly owned subsidiary in Seattle, WA, U.S.A. For more information, please visit Epigenomics' website at www.epigenomics.com.
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