JAMA Reports that the NMP22(R) BladderChek(R) Test is Better at Detecting Bladder Malignancies than Current Technologies

A simple point-of-care urine test, the NMP22 BladderChek Test, was found to significantly increase the detection of recurrent bladder cancer, finding 99% of the malignancies when used with cystoscopy, according to a report in the January 18 issue of the Journal of the American Medical Association (JAMA).

The lead author, H. Barton Grossman M.D. at the M. D. Anderson Cancer Center stated, "This study confirms the prior BladderChek investigation published in JAMA early last year-- NMP22 BladderChek combined with cystoscopy detects significantly more cancers than cystoscopy alone.

Because bladder cancer has a very high recurrence rate, we need to monitor patients vigilantly. Adding the NMP22 test to routine monitoring provides an extra measure of confidence. This test has important advantages over other methods: it provides results while the patient is at the doctor's office and as a molecular marker it can detect cancers that might be missed visually without requiring intact cells. No other test is FDA approved for both diagnosis and monitoring that can be used during a patient visit and costs less than cytology."

When used in combination with cystoscopy, a visual examination of the bladder, the NMP22 BladderChek test detected 99% of bladder malignancies compared to 91% for cystoscopy alone. The BladderChek test was positive for 8 of 9 cancers not seen by cystoscopy, including seven tumors that were aggressive or advanced.

The BladderChek test also detected four times as many cancers as the commonly used laboratory based urine cytology test. The authors of the study, who include clinical investigators at the University of Texas M. D. Anderson Cancer Center, the University of Miami School of Medicine, the University of Rochester Medical Center, Rhode Island Hospital, and community based clinicians, recommended using the NMP22 BladderChek(R) Test in the routine monitoring and management of bladder cancer patients.

They noted that it is an inexpensive and a cost-effective tool, proven to detect significantly more cancers than urine cytology, and at half the cost. When combined with cystoscopy the NMP22(R) test improves the detection of cancer. Unlike all cell-based urine tests it does not require laboratory time and facilities and expert analysis. This point-of-care test provides unambiguous results during a patient's visit.

"NMP22(R) BladderChek(R) Test is an important tool for doctors--early detection of bladder cancers, both initial and recurrent, improves treatment options and patient outcome," said Edward Messing M. D., Chairman of the Urology Department at the University of Rochester Medical Center. "Delay of diagnosis of an aggressive bladder cancer even by a few months can affect prognosis. The AUA guidelines for evaluation of patients with blood in the urine recommend using a urine test as back up to cystoscopy. We use the NMP22 test in our practice, and will include it in an upcoming National Cancer Institute (NCI) study for monitoring bladder cancer recurrence after treatment."

Bladder cancer has the highest rate of recurrence of any malignancy, with the cancer recurring in 50% to 90% of patients, depending o­n the aggressiveness and extent of the initial tumor. Patients are rigorously monitored throughout their lives for new malignancies.

A combination of methods is used to monitor patients since no single method is 100% accurate in detecting the cancer. The prevalence of bladder cancer in the United States is higher than lung cancer; and its prevalence in women is similar to the number of women with cervical and ovarian cancers. Currently there are 500,000 Americans with a history of bladder cancer. Developed and commercialized by Matritech (Amex: MZT), a leading developer of protein-based diagnostic products for the early detection of cancer, the NMP22 BladderChek Test is the o­nly noninvasive point-of-care assay approved by the FDA as an aid in both the initial diagnosis and monitoring of bladder cancer. Using o­nly four drops of urine, the test detects elevated levels of the nuclear matrix protein NMP22 and results are available during the patient visit.

"Bladder cancer is the second most common urologic malignancy in the U.S. after prostate cancer," notes investigator and author Mark Soloway M.D., Chairman, Department of Urology at the University of Miami School of Medicine. "We have made dramatic changes with the use of PSA, an early detection program, and tremendous public awareness. Unfortunately, we have not done the same with bladder cancer. o­ne quarter of all bladder malignancies are still first diagnosed after they have become invasive, so treatment is more difficult and prognosis is worse. This hasn't changed in 20 years. The NMP22 BladderChek test is an important step forward. Not o­nly has it been demonstrated in two large studies to improve detection of new and recurrent cancers, it provides an easy and inexpensive way for primary care doctors to screen patients we know are at higher risk for bladder cancer: people who smoke, are exposed to chemicals or have blood in their urine."

Because of the high recurrence rate of bladder cancer, patients who have had the disease are typically evaluated for new tumors every three months for the first two years after surgery, twice a year for the next two years, and yearly after that, until a recurrence is diagnosed, at which point monitoring resumes at three month intervals. Early detection is key to extending and providing quality of life for patients, and reducing treatment costs. The five year survival rate is 94% for patients diagnosed with early stage, or noninvasive cancer, while patients with metastatic or advanced stages of the disease have as low as a 6% chance of surviving five years.

Early detection of bladder cancer in haematuria patients: vision becomes reality

Oehr P. University Bonn, Medical Faculty, Bonn, Germany

Introduction & Objectives

Due to lack of easy to handle point of care (POC) assays and no significant changes in routine follow up of haematuria patients with suspected cancer, the number of cases with early detected urinary bladder cancer seems to have remained unchanged during the last decades. The objective of the presented study was to investigate the diagnostic power of the new Matritech NMP22-BladderChek® POC assay.

This qualitative POC-assay is based o­n a 30 min. Chromatographie analysis of 4 drops fresh voided urine at room temperature including antigen detection by anti-NMP22-(nuclear matrix proteinl-antibodies. Excluding patients with urocystitis, stones, urinary tract infections and incorporated catheters, and prior to endoscopy, 212 haematuria patients in 16 urologic practitioners' sites were investigated

Newton, MA (February 15, 2005) — According to a study published today in the Journal of the American Medical Association (JAMA), Matritech’s (Amex:MZT) NMP22^®BladderChek^® Test detects cancers missed by cystoscopy, the medical reference standard used to diagnose bladder cancer. The NMP22^®BladderChek^® Test is the o­nly FDA approved point-of-care, or in-office test, for the diagnosis of bladder cancer. The researchers concluded that the BladderChek^® Test can increase the accuracy of cystoscopy in diagnosing bladder cancer, with results available during the patient’s visit.

The authors, who include independent investigators at the University of Texas M.D. Anderson Cancer Center, the University of Rochester Medical Center, the University of Miami School of Medicine, and community based clinicians, reported that when used with cystoscopy, the NMP22^®BladderChek^® Test detected 94 % of the bladder cancers, compared to 89% seen by cystoscopy alone. In addition to identifying four invasive, life threatening cancers missed during cystoscopic examination, the point-of-care test detected over 3 times as many malignancies as cytology, a laboratory based urine test. The study included 1,331 patients from 23 sites in 10 states.

The NMP22^® BladderChek^® Test was developed following the discovery by Matritech’s scientists of a nuclear matrix protein, the NMP22^® protein that is elevated in the urine of patients with bladder cancer. Matritech is a leading developer of protein-based diagnostic products for the early detection of cancer. Based o­n its proprietary nuclear matrix protein (NMP) technology, the Company’s scientists discovered that the NMP22^® marker proteins were elevated in the urine of patients with bladder cancer. NMPs are proteins associated with DNA replication and RNA synthesis and have been reported to be elevated or overexpressed in cancer cells. This discovery has led to the development and the FDA approval of the point-of-care NMP22^® BladderChek^® Test, which was evaluated by a team of independent urologists and clinicians; it is their findings that are reported in today’s special biotechnology issue of JAMA.

The BladderChek^® Test was also shown to be more effective than cystoscopy alone in detecting later stage bladder cancers. Of the total patients enrolled in the study, 79 had malignancies and 10 of those were muscle invasive. Initial cystoscopy visualized 60% of the invasive tumors, compared with the BladderChek^â Test which was positive for 90% of the people with the life threatening condition. By comparison, cytology was positive for o­nly 22% of the patients with muscle invasive cancer. The BladderChek^â Test was also positive for a patient with carcinoma in situ (cancer that had not spread to surrounding tissues) after an initial cystoscopy report of benign disease.

“Early detection in cancer is the key to saving lives. We found that when cystoscopy and the NMP22^® Test are used together, they detect bladder cancer at a 94% rate,” stated the study’s lead author and principal investigator, H. Barton Grossman, M.D., Deputy Chairman, Department of Urology, M.D. Anderson Cancer Center in Houston, TX.
“In our study, the test identified several malignancies, including life threatening tumors, missed by the initial cystoscopy.”

Also commenting o­n the study, Stephen D. Chubb, Chairman and CEO of Matritech said,
“These results are an important validation of the clinical utility of the BladderChek^® Test and our NMP technology. They also have important implications for medical practice; with the BladderChek^® Test doctors can screen patients who are at elevated risk for bladder cancer with a non-invasive procedure. Diagnosing cancer early, when it is at its most curable stage, is the key to saving lives. Being able to treat cancer early improves the patient’s prognosis and quality of life. Our goal is to provide clinicians and patients with an effective, convenient, rapid and low cost cancer diagnostic aid that can increase diagnostic accuracy and confidence.”
Mr. Chubb added,
“And we are succeeding in achieving that goal. During 2004 an increasing number of urologists incorporated the NMP22^®BladderChek^® Test into routine use both here and in Europe. These physicians are using the BladderChek^® Test for diagnosis as well as for monitoring patients with a history of bladder cancer. In the United States, where the BladderChek^® Test is Medicare reimbursable, we are able to make it available at approximately half the cost of cytology.”

About the Study
The blinded study was designed to evaluate the clinical utility of the NMP22^®BladderChek^® Test, a new point of care proteomic test, in enhancing the detection of bladder cancer. The performance of the NMP22^®BladderChek^® Test, that measures the NMP22^® nuclear matrix protein in urine, was compared to voided urine cytology , which must be analyzed in a clinical laboratory, as an aid to cystoscopy in diagnosing bladder cancer.

About the NMP22^® BladderChek^® Test
The NMP22^®BladderChek^® Test is the o­nly in-office test approved by the FDA for the diagnosis of bladder cancer. The NMP22^®BladderChek^® Test is a painless and non-invasive assay that detects elevated levels of the NMP22^® protein o­n a single urine sample. Healthy individuals generally have very small amounts of NMP22^® protein in the urine. The level of NMP22^® protein, however, is often elevated in the urine of patients with bladder cancer, even at early stages of the disease. The BladderChek^® Test, which has an average cost of about $30, is more cost effective than laboratory based cytology tests. It can be performed in a physician’s office with results available during the patient visit, allowing a rapid, accurate and cost-effective way to aid in the detection of bladder cancer. The use of the NMP22^® protein has been approved by the FDA four times for various formats and claims, most recently in April 2003 for point-of-care use for diagnosis.

About Cystoscopy
Cystoscopy is performed by the urologist. Local anesthesia is administered and a cystoscope (a telescope-like tube with a tiny camera attached) is inserted into the bladder through the urethra to allow the physician to detect abnormalities.

About Bladder Cancer
Bladder Cancer is the fifth most common form of cancer in the United States and the ninth most common form of cancer in the world today. The American Cancer Society estimates that over 63,000 new cases of bladder cancer will be diagnosed in the United States this year ( over 47,000 men and 16,000 women), and over 13,000 people will die of the disease (nearly 9,000 men and 4,000 women). Worldwide it accounts for 330,000 new cases and 100,000 deaths each year. It is also o­ne of the most chronic cancers, recurring in almost 70% of patients.

Bladder cancer occurs primarily in men age 60 and older and roughly twice as frequently in white men as in black men. Men are four times more likely to be diagnosed with bladder cancer than women; age-adjusted mortality rates from bladder cancer are similarly higher for men than for women. Among U.S. males, the incidence of new bladder cancer cases is almost as large as the incidence of colon cancer.

The most common risk factor for bladder cancer is smoking. Smokers are four to seven times more likely to get bladder cancer as nonsmokers. In the United States, smoking is estimated to be associated with about 50% of bladder cancer deaths among men and 30% among women. The most common symptom of bladder cancer is blood in the urine, a condition referred to as hematuria.

Occupational exposures to chemicals (aromatic amines) used in dry cleaning facilities and the production of dyes, paper, rope, apparel, rubber and petroleum products have been associated with increased risk for bladder cancer. Other industrial exposures implicated as risk factors for developing bladder cancer include combustion gases and soot from coal, chlorinated aliphatic hydrocarbons, and chlorination by-products in heated water.

If diagnosed in its early stages, the five-year bladder cancer survival rate is over 90%. At an advanced stage, however, the five-year survival rate can be less than 10%. It has been estimated that this year in the United States about 25% of bladder cancer tumors will be diagnosed after they have become invasive or metastatic, significantly lowering the five year survival rate.

About Matritech
Matritech is using its patented nuclear matrix protein (NMP) technology to develop diagnostics for the detection of major cancers. The Company's first two products, the NMP22^® Test Kit and NMP22^®BladderChek^® Test, have been approved for both the monitoring and diagnosis of bladder cancer. The NMP22^® products are based o­n Matritech's proprietary NMP technology, exclusively licensed from the Massachusetts Institute of Technology, which correlates levels of NMPs in body fluids or cells to the presence of cancer. The Company has discovered other proteins associated with cervical, breast, prostate, and colon cancer and is, with its own research staff and through strategic alliances, in various stages of research and development currently targeted to applications for cervical, breast and prostate cancer. For more information about Matritech consult its web site at www.matritech.com.

Statement under the Private Securities Litigation Reform Act
Any forward-looking statements related to the Company's currently marketed products, their utility and market acceptance compared to other currently available technologies, as well as to the Company’s present expectations about further development of products and technologies, are subject to a number of risks and uncertainties, many of which are beyond the Company's control. These include risks and uncertainties related to obtaining and maintaining regulatory approvals, market acceptance of and continuing demand for the Company’s products, the impact of competitive products and pricing, technical challenges in completing product and technology development, and health care reform. These and other risk factors are described in the Company's periodic reports and registration statements as filed with the Securities and Exchange Commission. These forward-looking statements are neither promises nor guarantees. There can be no assurance that the Company's expectations for its products or future financial performance will be achieved. Readers are cautioned not to place undue reliance o­n these forward-looking statements, which speak o­nly as of the date hereof. Matritech undertakes no responsibility to update any such forward-looking information.

Contact for Matritech:
Kathleen O'Donnell
617-928-0820 X270

Written by JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (JAMA), 2005

• 23 clinical sites, in 10 states, enrolled 1,331 patients at risk for bladder cancer
• 79 of 1,331 (6 %) patients diagnosed with bladder cancer
• Of 10 with muscle invasive bladder cancer:
• NMP22 BladderChek Test was positive in 9/10 (90%)
• Voided urine cytology test was positive in 2/9 (22%)
• Of the 79 cancers diagnosed, the NMP22 BladderChek Test:
• Detected 3x as many tumors as cytology 
•  Identified 32 malignancies missed by cytology
• Detected 4 cancers not visualized during initial cystoscopy (3 of 4 were muscle invasive)
• NMP22 BladderChek Test specificity 90% for patients with no UT disease
• NMP22 BladderChek Test accuracy 83.7%
• NMP22 BladderChek Test plus cystoscope detected 94% vs. 89% with cystoscopy alone

Cytology detected o­nly 1 cancer that was neither visualized by the cystoscope nor detected by the NMP22 BladderChek Test

Conclusion of the study by its authors:

Combining cystoscope with noninvasive point-of-care assay for urinary NMP22 proteins can increase the accuracy of cystoscopy with results available during the patient visit. NMP22 BladderChek Test is less than half the expense of voided cytology.

Hematuria important early sign of bladder cancer

"We need to investigate everyone with it to save lives, but we end up investigating about 20 people with hematuria to find o­ne with bladder cancer," says Dr. Giora Katz, urologist. "This new BladderChek® Test helps us focus our search closer to those with cancer, expediting early diagnosis and helping the urologist to be more confident in determining the cause of hematuria."

"Hematuria work-up is quite expensive and involves invasive procedures and X-ray tests. Anything that can help direct attention to benign and malignant causes of hematuria is very helpful." Adds Dr. Katz, "The BladderChek Test is doing just that."

Case in point:

The Veterans Health Administration (VA) is the largest provider of health care in the country. Dr. Katz observed, "Most of the patients in the VA are at high risk for bladder cancer because they are males, older and have a history of smoking. The VA is spending a lot of resources to investigate and find patients with hematuria caused by cancer. The VA can use the BladderChek Test to help direct resources to patients with the highest suspicion of cancer." Dr. Katz concluded, "The BladderChek Test enhances the early diagnosis of bladder cancer. And, early diagnosis of bladder cancer can save lives."

Giora Katz, M.D., urologist is o­ne of the principal investigators and a co-author of the bladder cancer multi-center study. He uses the NMP22® BladderChek® Test in his practice at Lakeshore Urology in Manitowoc, Wisconsin, as well as at the Lake City VA. Note: These statements by Dr. Giora Katz, physician and scientist, do not necessarily reflect the position of the Lake City VA Hospital in Lake City, Florida or Holy Family Medical Center in Manitowoc, WI. For more information contact Dr. Katz at 352-215-6335.

Bladder Cancer Facts:

Incidence is growing; smokers at greatest risk; early diagnosis key to survival
Stats: Bladder cancer is the 2nd most common urologic cancer; 63,000 cases diagnosed each year; fifth most common cancer in the US; highest rate of recurrence (50-85% recurrence within 6-12 months); 4x higher incidence in men than women; women have a higher mortality rate because typically they are diagnosed at a later disease stage.

According to the American Cancer Society:

The prevalence of bladder cancer in the U.S. has surpassed that of lung cancer, and among U.S. males there are almost as many new cases as colon cancer.

• The 5-year survival rate for patients diagnosed with bladder cancer is 95% when tumors are discovered while confined to the mucosa.
• Approximately 25% of bladder tumors are detected after they have become invasive or metastatic.
• As a result of delayed detection, an estimated 13,000 people in the U.S. will die of bladder cancer this year.
• A single episode of hematuria can prompt evaluation for bladder cancer, since blood in voided urine is among the most frequently observed symptoms of the disease. (Estimated 5% of patients with hematuria will have bladder cancer.)
• Cystoscopy is the primary diagnostic tool for bladder cancer. Accuracy of the diagnosis can be reduced by poor visualization resulting from inflammatory conditions or bleeding. Also, flat urothelial lesions may be difficult to distinguish from normal bladder tissue.
• Voided urine cytology is frequently used as an adjunctive noninvasive test. Cytology has high specificity, but is expensive and has low sensitivity (approximately 15% to 30% in early-stage cancers).
• NMP22 BladderChek Test provides molecular confirmation for the disease when cystoscopy results are suspicious and additional time is needed for a pathologist's determination regarding the status of the lesion. This FDA approved test is providing information regarding treatment steps and priority.
   

Bladder Cancer in Review JAMA, Feb. 16, 2005

The Journal of the American Medical Association reported researchers at the MD Anderson Cancer Center in Houston teamed with 22 other urology centers throughout the U.S. to investigate whether a new noninvasive urine-based test for a nuclear matrix proteomic marker for bladder cancer, NMP22, had clinical utility as an aid in diagnosing the disease. 1331 men and women were tested with the NMP22® Test.

The study population was 3:1 men vs. women with an elevated risk for bladder cancer due to various known risk factors (such as a history of smoking) and included patients with symptoms such as hematuria and dysuria.

According to the authors of the report in JAMA, "The NMP22 protein is the o­nly tumor marker approved by the FDA as an aid in the initial diagnosis of bladder cancer, and the test has been waived under the Clinical Laboratory Improvement Act so it can be performed in any physician's office. The cost of urine tests varies by location. The average Medicare reimbursement for voided cytology is approximately $56, compared with $24 for the NMP22 point-of-care assay."

Conclusion:

The authors found that the NMP22 Test could be a useful adjunct to cystoscopy for diagnosing bladder cancer.

Clinical Findings Reported in JAMA: > Applied in Private Practice

Orlando urologist Dr. Stan Sujka commented o­n the report in JAMA, "The Orlando Urology Associates have been using the NMP22® BladderChek® Test for six months. (They previously used urine cytology.) Using the NMP22 test has been a win-win situation for patients and our practice. We don't have the bias of the pathologist, there is less paperwork, and less anxiety among the patients, since it's a 30-minute test versus sending out a cytology test to a lab. There is less cost, and overall it's a great adjunct to cystoscopy. It helps streamline the patient care and is used for the bladder cancer work-up, as well as with hematuria work-ups. It's not 100% and patients should know that, but provides great information in a timely way."

Dr. Sujka is also o­n staff at MD Anderson in Orlando. During his residency in Buffalo, New York, Dr. Sujka saw patients living near the Love Canal. This population experienced a high incidence of bladder cancer. According to Dr. Sujka, bladder cancer is a by-product of exposure to carcinogens from the chemical and dye industries, but the most common cause is smoking. Dr. Sujka has previously authored papers and spoken o­n bladder cancer issues. For additional information, contact Dr. Sujka at his Orlando Office, 407-843-6645.

Bladder Cancer Diagnostic Challenge:

According to Kevin Tomera, M.D, urologist, Alaska Clinical Research Center, "It's disconcerting when a patient presents with symptoms of bladder cancer but has a negative cystoscopy. If the NMP22 BladderChek Test is negative, there is a combined 97% predictive value."

"If NMP22 BladderChek Test is positive, you are more likely to have an aggressive or high grade disease requiring treatment," says Dr. Tomera, o­ne of the principal investigators for the multi-center bladder cancer study. "The BladderChek Test has been shown to be 3 times more sensitive than cytology."

Although cystoscopy is the best diagnostic tool for allowing the physician to view the bladder, the NMP22 BladderChek Test provides confirmatory results at a molecular level.
"At every stage of the disease the NMP22 BladderChek Test provides a higher sensitivity than cytology for detection of bladder cancer. The NMP22 BladderChek test has the potential to save lives and reduce morbidity, as well as save health care costs," adds Dr. Tomera.

Benefits of NMP22® BladderChek® Test:

• Greater sensitivity compared to cytology
• Detects 3x cancers compared to cytology
• Can detect cancers not visualized during cystoscopy
• Results in minutes not days - results available in 30 minutes
• Less paperwork for nurses and office staff
• Healthcare cost savings - less expensive test (about $30), no outside lab fees or shipping costs
• Medicare reimbursable
  The o­nly FDA approved in-the-doctor's-office test for the diagnosis and monitoring of bladder cancer
• This test is not meant to replace cystoscopy, but is recommended to be used in combination with cystoscopy to increase diagnostic accuracy
  

About the NMP22® BladderChek® Test

The NMP22 BladderChek Test was developed and commercialized by Matritech, a Massachusetts based biotechnology company.

The NMP22 BladderChek Test detects elevated levels of the NMP22 protein in a single urine sample. Healthy individuals generally have very small amounts of NMP22 protein in their urine. NMP22 protein levels, however, are often elevated in the urine of patients with bladder cancer, even at early stages of the disease.

The NMP22 BladderChek Test, a painless and non-invasive assay, is the o­nly in-office test approved by the FDA for the diagnosis of bladder cancer. The BladderChek Test, which is reimbursed by Medicare at about $24, is more cost effective than cell-based laboratory cytology tests. It is approved for use in a physician's office with results available during the patient visit, allowing a rapid, accurate and cost-effective way to aid in the detection of bladder cancer. NMP22 Tests have been approved by the FDA four times for two formats and claims, most recently in April 2003 for point-of-care use for diagnosis.

For more information about Matritech consult the website at www.matritech.com .

Source: Matritech