Radionuclide imaging products that reliably detect cerebral amyloid deposits would be clinically useful in ruling out a diagnosis of Alzheimer’s disease in patients with cognitive impairment, according to a Food and Drug administration advisory panel.
At a meeting of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, the panel considered the clinical utility of investigational radionuclide imaging products that detect amyloid in the brain, but did not focus on a specific product.
None of the imaging products are close to being improved, but several companies have requested advice from the agency on designing phase III clinical trials for their products, which are used with PET scans to detect amyloid deposits in the brain, one of the two neuropathologic findings of Alzheimer’s disease (AD).
The proposed indications for these products are for determining whether a patient is amyloid-positive or negative, not for diagnosis of AD. For example, GE Healthcare’s proposed indication for its imaging agent is for detection for B-amyloid deposits in the brain. Bayer HealthCare Pharmaceuticals has proposed that its agents be indicated to detect B-amyloid plaque deposition in the brain, “and thereby assist the physician in the diagnosis (exclusion/detection)” of AD. The proposed indication for the agent under development at Avid Radiopharmaceuticals Inc. is “for PET imaging of amyloid plaque pathology in the brain to aid in the evaluation of patients with signs or symptoms of cognitive impairment.”
Chair of neurology at the Mayo Clinic, Scottsdale, Ariz., commented that the products could be useful in impaired individuals, but physicians would “have to be careful not to overcall AD since many elder patients will have modest amounts of cerebral amyloid but may have many other reasons for cognitive impairment — stroke, drugs, infections, etc.”
GE Healthcare, Bayer, and Avid presented their plans for phase III studies at the meeting, including examples of positive and negative PET scans, and presenting evidence that as many as 20% of patients said to have AD are misdiagnosed.
One of the patients, of the department of psychology, University of Waterloo, Ont., said he would find amyloid imaging results “useful in clinical encounter” with patients, but it would not be the only tool used in making a diagnosis.
Another panelist, professor, vice chairman, and director of research at the MRI Institute at the University of California, San Diego, said that a negative test would be useful in determining that a patient does not have AD. A positive test, he added, would make it possible for the first time to determine whether a living patient has amyloid in the brain.
Wondered how much the results of amyloid imaging will matter in the absence of better treatments. Among patients who are misdiagnosed, most have another equally incurable diagnosis such as dementia with Lewy bodies or vascular dementia. The cost of amyloid imaging products also will need weighed carefully, especially in the absence of more effective therapy.
All but one panelist agreed that phase III clinical studies should compare the results of in vivo imaging with postmortem histopathologic results to determine that accuracy of the imaging products. Several panelists noted that it can take a long time to obtain autopsy data.
“We have the amyloid opportunity to correlate amyloid imaging with clinical and genetic status. . . . So I could see the case for moving this along now without requiring autopsy correlation.” Maybe its uses, however could be limited to real diagnostic dilemmas. Not every 80-year-old with slowly progressive memory loss needs this, but 50-year-old with no family history of AD, in whom a brain biopsy is being considered, might be better off with than a brain biopsy.”