Mixed Messages on Alzheimer's Test

There's a stark contrast in the media coverage of yesterday's FDA advisory committee meeting on a test for a signature feature of Alzheimer's disease. At The New York Times, Gina Kolata's cup of enthusiasm is at least half full:

F.D.A. Sees Promise in Alzheimer's Imaging Drug

An advisory committee to the Food and Drug Administration recommended unanimously Thursday that the agency approve the first test--a brain scan that can show the characteristic plaques of Alzheimer's disease in the brain of a living person. The approval was contingent on radiologists agreeing on what the scans say and doctors being trained in how to read the scans.

The article quotes Alzheimer's experts enthusing about "a monumental step forward," and "a landmark day for our field."

Several other outlets, including CNN Health, took more of a glass-half-empty approach:

FDA on new Alzheimer's test: No, or at least not yet

A new test to detect or rule out Alzheimer's is not quite ready for prime time, an FDA advisory panel said Thursday afternoon. The test, a type of PET scan developed by Avid Radiopharmaceuticals, is designed to detect the telltale buildups of amyloid plaque in the brain that signify Alzheimer's disease.

In fact, as Alzforum reports in a detailed analysis of the decision, the committee first voted 13-3 to reject Avid's new drug application, then voted unanimously that they would recommend approval if the company can bolster its argument that the scans are read consistently by different doctors. Doing that is likely to require refinements to the protocols for reading the scans and training and education programs for neuroradiologists.

The Alzforum article also notes a point that receives almost no mention elsewhere: that Avid's application actually does not seek approval to use the test to diagnose Alzheimer's disease. Rather, it seeks approval to use it to rule out the presence of amyloid plaques. If FDA eventually grants approval, presumably some doctors would use it for "off-label" purposes, such as testing people they already suspect have Alzheimer's or screening people with mild memory impairments.

Avid's compound is based on a radioactive isotope of fluorine (F-18) that is injected prior to a PET scan to enable doctors to detect amyloid deposits in the brain. It's one of several F-18 compounds in development for this purpose. The very first amyloid imaging method, developed nearly a decade ago, was based on a short-lived isotope of carbon, C-11, limiting its use to hospitals with their own cyclotron that could manufacture it onsite. The new F-18 compounds could be much more widely used.

An important confirmation that the Avid compound accurately detects plaques comes from a study in this week's issue of The Journal of the American Medical Association, which shows good agreement between PET results and autopsy findings in 35 patients.

But do patients really want to know they have incipient Alzheimer's disease? It's true that knowing a loved one has Alzheimer's can help families plan for the rough road ahead, and ruling the disease out can help neurologists zero in on the correct diagnosis. But the lack of disease-modifying treatments for Alzheimer's may dissuade some people from getting tested.

For now, the F-18 PET compounds may be more useful for researchers than clinicians. They're already being used in clinical trials and in the major government- and industry-sponsored Alzheimer's Disease Neuroimaging Initiative (profiled in Science). Many researchers believe the use of amyloid imaging and other biomarkers can help improve clinical trials—by helping to exclude patients with other conditions, for example, and identifying patients with early stage disease. When treatments finally do become available, they're likely to be most effective when given early--and then the demand for Alzheimer's tests should really take off.