Alzheimer's Club

"Nymox Pharmaceutical’s AlzheimAlert diagnostic fails to improve the decision-making capability of physicians assessing patients for Alzheimer’s disease, FDA’s Immunology Devices Panel concluded July 15.

The panel voted 5-2 against recommending approval of the clinical test. Both positive and negative test results from the device “appear to have little clinical utility,” panelist James Gulley (National Cancer Institute) said of the clinical data.

The firm suggested its product would be especially useful in assisting general practitioners. However, Gulley was among several other panel members who argued that primary care physicians would likely refer the patient to a specialist following an AlzheimAlert test, regardless of the result.

Nymox wants to position the product as an adjunct to standard Alzheimer’s evaluation procedures such as neurological, radiological and neuropsychological techniques, and as a tool to “help the clinician’s decision for the need of further diagnostic work-up.”

The urine test measures levels of neural thread protein (NTP), which has been shown as elevated in patients with early Alzheimer’s disease (AD).

The panel’s conclusion is consistent with FDA’s statistical review. The agency suggested that Nymox’ data did not offer any clear answers because it was not compared to the “gold standard” for AD diagnosis – histopathological autopsy of the brain after death.

“Should a clinician discard the clinical impression of [definitive] non-AD if the NTP test is positive?” FDA statistician Mariana Kondratovich inquired. “From the submitted data, it is impossible to evaluate the significance of this disagreement.”

Nymox’s application rests on one 200-patient, nine-center study comparing NTP results with standard clinical assessment by neurologists. “First-morning” urine samples were collected from subjects with signs of dementia, but not an AD diagnosis.

Subsequently, physicans – blinded to the test results – employed current best practices to put patients into one of four categories: definite non-AD, mild cognitive impairment, possible AD, and probable AD.

Nymox intends the test to “aid in the diagnosis of definite non-AD versus probable AD, possible AD, or MCI.”

The firm reported that 94 of 98 (96%) patients with NTP values > 22 microg/mL were classified in one of the latter three categories. It also noted that 40 of 44 (91%) def non-AD patients had NTP values < 22 microg/mL (categorized as “normal”).

However, 62 of the 102 patients with “normal” NTP values were not classified into the non-AD group, suggesting that 61% of patients “will be incorrectly categorized as having def non-AD,” FDA reviewers noted in documents released prior to the meeting.

“Given the significant overlap observed in NTP values between the four categories of interest...it is unclear if this device is effective at meeting the stated indications for use,” the pre-panel analysis stated.

Nymox contends that AlzheimAlert is not intended to individually support a physician’s decision, but to add helpful data to the overall clinical picture, which, they say, is a use supported by the submitted study.

“It is infinite, the number of choices in the practice of medicine,” Nymox CEO Paul Averback told the panel. “We are only trying to say that [the product] adds information to the toolbox.”

However, FDA and several panelists agreed that the test does not address the complexities of today’s diagnostic challenges. Agency reps suggested that the definite non-AD category was not clearly defined, and that many assigned to the group were unlikely to be confused for AD patients.

“How useful is a diagnostic test that is only applicable in those instances where a diagnosis is already easy to make?” Division of Neuropharmacological Drug Products Medical Officer Ranjit Mani, who reviewed the PMA clinical data as a consultant.

Several panel members echoed this concern wishing the test would differentiate patients in the probable AD and MCI categories, where more complex signs and symptoms present themselves.

FDA approval would allow Nymox to sell AlzheimAlert as a kit to qualified laboratories and hospitals. Currently, it is offered to physicians through Nymox’s CLIA-certified laboratory in N.J."

Source: Nymox AlzheimAlert Diagnostic Clinical Utility Questioned By Panel. FDA Advisory Committe .com (20 July 2005) [FullText]