Diagnostics & Imaging Week Associate

Applied NeuroSolutions (APNS; Vernon Hills, Illinois) has moved a step closer to becoming the first company with an FDA-approved diagnostic test for Alzheimer’s disease (AD) with its disclosure that it has submitted a pre-IDE (Investigational Device Exemption) application to the FDA.

The company said the submission was a “milestone” in its bid to commercialize its cerebrospinal fluid (CSF) diagnostic AD test.

The pre-IDE application process is designed to provide companies that have unique diagnostic tests with informal input regarding what the FDA would look for in a formal IDE application.

“We’re excited to submit our pre-IDE and begin to get important feedback that will allow us to move forward in our quest to bring our CSF AD diagnostic test to market,” said John DeBernardis, PhD, president and CEO of APNS in an interview with Diagnostics & Imaging Week. “The [potential] patient population is enormous, you’re looking at potentially anybody over the age of 60 to get screening so you could be looking at hundreds of thousands of patients.”

“The submission of our pre-IDE application is the first step in a process towards commercialization,” said David Ellison, company CFO. “We anticipate the next steps to include meetings with the FDA and our advisory committee to review and further refine our protocols. Following these meetings, we anticipate filing our IDE and beginning clinical trials in the first quarter of 2006.”

The CSF test measures levels of a genetic marker found in the body called p-tau231, and the company said it appears that high levels of this market may indicate a proclivity toward acquiring AD.

In partnership with Peter Davies, PhD, and a scientific team at Albert Einstein College of Medicine (New York), the company’s CSF test has detected AD at a very early stage with 85% to 95% accuracy in more than 3,000 patient samples reported thus far.

While the IDE path is important to the company so that it may commercialize the test in the U.S., DeBernardis said APNS also is exploring another avenue, a CLIA (Clinical Laboratory Improvement Amendments of 1988) waiver exemption to make the test available to the research and medical community within months “as opposed to sometime in 2007 through an FDA approval.” However, he noted that route would not make the device approved for the diagnosis of AD; rather, he said, it would essentially be a research tool.

Current methods of diagnosis may involve blood work-ups to rule out other diseases, psychometric tests and magnetic resonance images, and APNS said the current cost of diagnosis may range from $1,000 to $4,000. The only conclusive way to diagnose AD at this point is through biopsy or autopsy to determine the presence of amyloid plaques in the brain. Tests such as those being developed by APNS could lower those costs of diagnosis, the company said.

Results of a study reported in the January 2004 issue of Archives of General Psychiatry, a publication of the American Medical Association (Chicago), showed that APNS’ diagnostic test outperformed in four of five categories the diagnostic test of its nearest competitor, the company said.

In the study, researchers confirmed that diagnostic tests developed by APNS, Innogenetics (Antwerp, Belgium) and Mitsubishi Chemical (Tokyo) each were successful in distinguishing between persons who had AD and those who had no disease at all. The Innogenetics and APNS diagnostic tests also were successful in distinguishing between patients with AD and patients with other forms of dementia, as well as patients with various mild psychiatric or neurological symptoms.

However, the APNS diagnostic test outperformed both the Innogenetics and Mitsubishi tests in four of the five categories, particularly in distinguishing frontotemporal dementia from AD, the company said.

The study involved 206 patient samples, of which 108 had Alzheimer’s disease, 52 had other forms of dementia and 22 had mild psychotic or neurological symptoms, and the rest were normal controls.

As part of its effort to bring an AD test to market, APNS has formed an advisory committee to assist in the actual IDE filing, noted DeBernardis. The six-person committee, the company said, “includes some of the best and brightest in Alzheimer’s disease research.” It is being led by Davies, APNS’ founding scientist and current scientific director.

The company estimated that there are about 2 million new patients annually worldwide who are candidates for a CSF diagnostic test for Alzheimer’s disease. In the U.S. alone, it projects an $80 million to $160 million annual market potential. The company also is developing a blood serum-based screening test, as well as a new class of therapeutics to treat AD.

According to DeBernardis, many people have asked him why having an earlier diagnostic test for AD is important right now, given the fact that there is no cure for the disease.

He said that currently, the diagnosis of AD is made at a point in which considerable neuronal damage has already occurred and the compounds that are available for treating the condition – such as Aricept and Exelon – really need intact neurons to be effective. “If you don’t have the neurons, the compounds are not going to be working.”

By being able to detect potential symptoms of the disease before its onset (pre-AD) during what he called the mild cognitive impairment (MCI) stage – a stage in which potential patients have cognitive problems but no dementia – DeBernardis said patients would at least have a head start in getting the help they need to alleviate the degenerative affects of the condition.

“The data that we have strongly suggests that this test may be useful in a prognostic sense of being able to predict which of those MCI patients are going to actually ultimately get Alzheimer’s.”

He also noted that Aricept and Exelon, made by Pfizer (New York) and Novartis (Basel, Switzerland) respectively, are currently in clinical trials for treatment of MCI patients and that if they are approved for those patients, it could at least enhance their quality of life for several more years. He also held out the promise for a more effective treatment in the coming years.

In any case, DeBernardis said, “early diagnosis is important.”