CDU Associate

Two companies received FDA clearance last month for new cardiac diagnostic tests that could greatly aid in the rapid detection of a potential heart attack, and one in particular could be the wave of the future for emergency room diagnosis of that condition.

Response Biomedical (Vancouver, British Columbia) reported receiving regulatory clearance to market two additional RAMP Cardiac Marker Tests, one for detecting troponin I and the other for detecting CK-MB, to assist in the rapid diagnosis of heart attack or acute myocardial infarction (AMI), a leading cause of death worldwide. The company had previously received FDA clearance of the RAMP Reader for general clinical use and of the RAMP Myoglobin Assay. Response said it anticipates commercially launching all three RAMP Cardiac Marker Tests in the U.S. and internationally beginning sometime in the middle of the year.

In another FDA action, Roche Diagnostics (Basel, Switzerland) was given the green light for sale of its Elecsys troponin T STAT test as an aid in the differential diagnosis of acute coronary syndrome, for risk stratification in patients with acute coronary syndrome and for cardiac risk in patients with chronic renal failure.

Response Medical's RAMP test is designed to provide a quantitative result in about 15 minutes, compared to several hours turnaround time for traditional laboratory testing. In clinical applications, the RAMP System is designed for use by healthcare professionals at the point of care (POC), including physicians' offices, medical clinics, hospital emergency departments and laboratories worldwide. Cardiac markers are proteins released in the blood following damage to heart tissue, which may represent a heart attack. Myoglobin, troponin I and CK-MB are the three most commonly used markers measured to assist in the diagnosis of AMI. While all three are currently used, Troponin I is broadly recognized as the cardiac marker of choice allowing for increased sensitivity and specificity in diagnosing AMI.

"I guess what we're most pleased about is really the overall performance we've shown on the platform as it applies to each [cardiac] test," said Bill Radvak, president and chief executive officer of Response. While the company is obviously pleased with all three approvals, Radvak told Cardiovascular Device Update that the troponin I test is probably the most important for it in this sector. "The sensitivity of our troponin I is truly lab quality, and that's where we can differentiate ourselves from the immunoassays of the past. Physicians will not have to sacrifice the level of information they get while still obtaining the results in 15 minutes, and that's really the breakthrough."

While the troponin I test is the most important of the three, he noted that it is still important to have the others, since different parts of the world are still using those tests. "However, the world is quickly moving towards troponin I as the primary, and potentially, sole marker," Radvak said. He said that an estimated 35 million troponin I tests are done worldwide on an annual basis.

The 510(k) regulatory clearance for the troponin I test follows a company-sponsored, dual-predicate clinical trial using a competitive POC device and a leading central lab-analyzer. The high-sensitivity RAMP troponin I test showed strong correlation with the lab analyzer and significant performance improvement vs. an FDA-cleared POC device at low troponin I concentrations. Both correlation and sensitivity are key performance criteria for clinical decision makers and provide significant product differentiation opportunity for Response's marketing efforts.

The RAMP System consists of a portable fluorescent Reader and single-use, disposable test cartridges. In biodefense, RAMP tests also are commercially available for detecting anthrax, ricin and botulinum toxin. The company is currently exploring development opportunities in infectious diseases including rapid tests for severe acute respiratory syndrome and West Nile virus.

"Given growing market recognition that RAMP is the only immunoassay platform that provides lab quality information in minutes, the company will continue to build its international distribution network over the coming weeks and months," Radvak said. He said the RAMP Cardiac Marker Tests represent a "strategic beachhead" into the medical testing market for future potential applications in stroke, oncology, and infectious diseases, with the last of the three being Response's next focus.

The company noted that the U.S. market alone for POC cardiac marker tests in 2004 is estimated to be around $150 million. The world cardiac rapid assay market is expected to achieve an average annual growth rate of 20% to 25% for the near future. Each year in the U.S. about 8 million Americans are admitted to emergency rooms for severe chest pain associated with suspected AMI. Only about 10% of those patients hospitalized are subsequently determined to have suffered a heart attack. The majority is eventually diagnosed with strained muscles, angina or heartburn. The total cost of unnecessary admissions and misdiagnosis is estimated to be more than $4 billion, and misdiagnosed heart attack cases also account for nearly 25% of malpractice claims against emergency room physicians.

"The RAMP System will dramatically improve the ability of physicians to quickly and accurately diagnose heart attacks within the critical window before irreversible heart damage or death occurs, improving patient care and preventing unnecessary hospital admissions associated with symptoms often mistaken for cardiac arrest," said Radvak.

The global POC market generated revenues worth $3.3 billion in 2002 and is expected to reach $5.5 billion in 2009, according to Response. In fact, that market is growing faster than the total in vitro diagnostics market.

"With increasing revenue from sales of multiple RAMP products in biodefense and infectious disease testing, FDA clearance of the company's lead medical products is a historic milestone and significant step in the further commercialization of RAMP as an entirely new class of diagnostic for multiple large market opportunities in clinical and non-clinical applications," Radvak said.

In the clinical arena, he said the company was looking to sell the RAMP Reader for around $3,000, but that one device can be used to perform multiple tests, which he said was a key market driver. He also noted that the company is looking at commercializing at least five tests a year from the various sectors in which it is involved.

Roche Diagnostics said the Elecsys troponin T STAT test also may be useful for the selection of more intensive therapy and intervention in patients with elevated levels of cardiac troponin T. The test measures the level of troponin T, a cardiac-specific protein, in a patient's blood. Troponin T is released into the blood when heart cells die, and its presence can help a physician diagnose heart attack. The higher the level of troponin T, the more at-risk the patient is to suffer another heart attack.

Roche said the new FDA clearance means that cardiologists and nephrologists can use the Elecsys troponin T test to evaluate a kidney disease patient's cardiac risk.

"The FDA clearance for the expanded indications for troponin T testing in patients with renal failure will change the way we approach the epidemic of cardiovascular disease in this high-risk patient group," said Benjamin Freda, MD, of the department of internal medicine at the Cleveland Clinic Foundation (Cleveland, Ohio). "Cardiac troponin T testing with the highly sensitive assay designed by Roche Diagnostics will help nephrologists and other physicians caring for patients with renal disease to address the epidemic of cardiovascular disease in this extremely high-risk group, using a practical, evidence-based, highly reliable test."