New Data Demonstrates ProMark™ Accurately Predicts Prostate Cancer Aggressiveness and Pathological Outcomes

CAMBRIDGE, Mass., June 2, 2014 /PRNewswire/ -- Today, for the first time, Metamark presents results from the clinical validation study that showed ProMark™, the first and only proteomic-based imaging biopsy test, achieved its primary endpoint by accurately differentiating between aggressive and non-aggressive forms of prostate cancer at early stages of disease. ProMark™ was shown to predict which patients have low-risk disease with a sensitivity of 90 percent or better, confidently identifying patients who are appropriate for active surveillance or need aggressive therapy. The data are being presented at the 2014 Annual Meeting of the American Society of Clinical Oncology (ASCO).  

"These results reinforce ProMark™ as a critical tool that has the potential to improve prostate cancer care by fulfilling the unmet need for more precise prognostic testing, which may benefit a significant number of the more than 200,000 men in the U.S. diagnosed annually who may be appropriate for active surveillance," said Fred Saad, M.D., F.R.C.S., Professor and Chief, Division of Urology, Director of Urologic Oncology, University of Montreal Hospital Center. "ProMark™ offers the oncology healthcare community a novel prognostic option to help confidently differentiate patients with more aggressive cancers from those with less aggressive disease, thereby enabling more personalized treatment decisions for our patients."

The results being presented are a culmination of three clinical studies. The first study identified 12 biomarkers that predicted both lethal outcome and prostate cancer pathology, and of those, eight were targeted in a clinical development biopsy study as the final subset for the ProMark™ test.

The third, blinded clinical validation study of ProMark™, which analyzed 274 prostate cancer biopsies, accurately predicted the overall prostate cancer pathology for patients with biopsy Gleason grades of 3+3 (=6) or 3+4 (=7). Quantitative measurements on the biopsy samples allowed researchers to successfully identify ProMark™ risk scores for 'favorable' cases (surgical Gleason score 3+3 or 3+4; organ-confined disease [<=pT2]) as potential candidates for active surveillance and 'unfavorable' cases (greater than or equal to T3a, N, or M or surgical Gleason >=4+3), more likely in need of aggressive therapy, with an AUC of 0.69 (0.61-0.74; p<0.0001) and odd's ratios lowest to highest quartile of 5.

Researchers found that patients with low-risk ProMark™ scores (<0.33) were accurately identified as having favorable disease 81 percent of the time, with 90 percent specificity, while high-risk scores (>0.8) indicating non-favorable disease were predicted 77 percent of the time. Importantly, the ProMark™ test was found to provide additional, independent prediction relative to standard risk-stratification systems, including National Comprehensive Cancer Network (NCCN) guidelines, the D'Amico system, and CAPRA, all using Prostate-Specific Antigen (PSA) levels, Gleason grades and T stage to group men as low, intermediate, or high-risk.

"A key challenge in treating men with prostate cancer is determining whether they need aggressive therapy, or if active surveillance is appropriate. Current clinical and pathological parameters are insufficient in predicting the risk of aggressive cancer for early stage cancer patients," said Peter Blume-Jensen, M.D., Ph.D., Senior Vice President and Chief Scientific Officer at Metamark. "ProMark™ was developed with the specific purpose to address this need. This latest data is a significant milestone for Metamark as it indicates ProMark™ can be used as an objective aid in decision making together with standard-of-care for prostate cancer prognosis, and thereby help maintain a higher quality of life for patients by avoiding unnecessary aggressive therapy, like surgical prostatectomy or radiation."

About the Studies
A clinical biopsy simulation study using prostatectomy tissue (N=380) was designed to identify 12 biomarkers that can predict both surgical Gleason score and lethal disease equally well from either low or high grade regions from each patient to represent biopsy sampling variation.  Next, a clinical study of 381 biopsies with matched prostatectomy annotation was done to select the best marker subset predictive of prostate pathology (surgical Gleason score and pathological T stage). Subsequently, the locked model was validated in a separate blinded clinical study with matched prostatectomy specimens (N=274). All biopsy Gleason grading was centralized and blinded.

About Prostate Cancer[i]
A dilemma confronts many of the 233,000 men in the United States who will be diagnosed this year with prostate cancer based on biopsy sampling. Although prostate cancer is a leading cause of cancer deaths among men, killing roughly 29,480 annually, the majority of prostate tumors are indolent and associated with little risk to health or longevity. The dilemma arises from the difficulty in distinguishing between aggressive and indolent tumors as crucial medical decisions are being made, especially for the about 205,000 men with biopsy Gleason scores of 3+3 and 3+4 who must evaluate their treatment options.[1]  Currently about 87 percent of these men with early stage prostate cancer elect aggressive therapy, although only 3-7 percent progress over lifetime. Aggressive therapy, most often in the form of radical prostatectomy or radiation, has significant side effects, such as incontinence and impotence, so addressing this significant overtreatment is critical.

About ProMark^™ 
ProMark™ is designed to improve the accuracy of prognosis for men diagnosed with prostate cancer, specifically the approximately 85% of prostate cancer patients with biopsy Gleason grades 3+3 or 3+4 for whom standard-of-care medical decision making is currently insufficient. The test measures the amount of specific protein biomarkers obtained by needle biopsy from regions of prostate tissue where the biomarkers are altered during tumor formation. These "regions of interest" are rendered as intact, paraffin-embedded tissue sections. Quantitative measurements of the biomarkers are then determined by means of imaging technology that is digitized and fully automated. The resulting analysis is thus completely objective and fully reproducible. A large, blinded, clinical-validation study of ProMark™ met its primary endpoint, demonstrating that the test can aid in differentiating between aggressive and indolent disease. The research program supporting ProMark™ has completed four clinical studies altogether, and additional prospective studies are underway. Metamark plans to commercialize ProMark™ in 2014 through the company's CLIA-certified laboratory in Cambridge, Massachusetts. For more information, visit: www.metamarkgenetics.com.

About Metamark
Metamark is a privately held biotechnology company founded in 2007 to develop novel, function-based, prognostic and diagnostic tests aimed at improving cancer care. The company's proprietary genomic and proteomic discovery platforms have yielded significant discoveries in several disease areas, including prostate, bladder, colon, and breast cancers. Through the acquisition of Healthtronics Laboratory Solutions last year, Metamark has become a leading provider of specialty urological pathology testing services throughout the United States. For more information, please visit the company's website at www.metamarkgenetics.com. Metamark™ and ProMark™ are trademarks of Metamark.

Forward-Looking Statement
This news release contains forward-looking statements that involve risks and uncertainties. These forward-looking statements are only predictions and are largely based on Metamark's current expectations. There are risks, uncertainties, and other important factors that could affect the accuracy of these statements, including those inherent in the process of discovering, developing, and commercializing products for use in humans. These risks may cause our actual results to differ materially from those results expressed or implied by these forward-looking statements. We do not expect to update any of these forward-looking statements after the date of this news release or to conform these statements to actual results. You should not place undue reliance on forward-looking statements contained in this news release.

Information about market and industry statistics contained in this news release is included based on information available to us that we believe is materially accurate. It is generally based on academic and other publications that are not produced for purposes of securities offerings or economic analysis. We have not reviewed or included data from all sources, and we cannot assure you of the accuracy or completeness of the data included in this presentation. Forecasts and other forward-looking information obtained from these sources, including estimates of future market size, revenue and market acceptance of products and services, are subject to the same qualifications and the additional uncertainties accompanying any forward-looking statements.

[i] National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. SEER Stat Fact Sheets: Prostate Cancer. http://seer.cancer.gov/statfacts/html/prost.html. Accessed April 28, 2014.

[1] Epstein JI, Feng Z, Trock BJ, Pierorazio PM. Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades. European Urology 61(5): 1019-24.

SOURCE Metamark