Among the limited tools available for the detection and diagnosis of Alzheimer’s disease (AD), molecular imaging for early detection of AD is an appealing one because it could allow for patient treatment prior to significant cognitive decline and extensive neurodegeneration. In addition, the ability to accurately detect and diagnose AD would be invaluable in clinical trials for the evaluation of potentially disease-modifying therapeutics.
What is Amyvid?
Amyvid (florbetapir F18/18F-AV-45) is a molecular imaging tool that is under investigation for use in the detection of beta-amyloid plaques in living brain. Based on the original technology using the 11C-labeled Pittsburgh Compound B (PIB) to bind amyloid plaques, the F18 radioligand is used in conjunction with positron emission tomography (PET) to visualize and quantify the amyloid burden in brain. With a radioactive half-life of 110 min, thereby increasing its ability to be transported significant distances away from manufacturing sites, F18 can be widely used by physicians and researchers.
How does Amyvid work?
Patients are injected with an intravenous bolus of F18 and about 50 minutes later PET images can be acquired. The F18 travels through the blood-stream and accumulates in the brain with high affinity for beta-amyloid. In a recent study, 30 minutes after injection it was clear that F18 was present in higher amounts in the brains of AD patients as compared to healthy volunteers1. The differences in brain scans between the two groups were still distinguishable 90 minutes after injection. None of the participants experienced adverse effects from the treatment and showed normal vital signs, echocardiograms and blood work after treatment1.
The quest for FDA approval of Amyvid
Amyvid is the lead beta-amyloid imaging agent in development for Avid Radiopharmaceuticals, Inc., which was acquired by Eli Lilly and Company in November 2010, and is the first compound of its kind to be considered by the U.S. Food and Drug Administration (FDA). The approval for marketing Amyvid as a non-invasive amyloid imaging ligand was contingent on an FDA-required formal Phase 3 histopathology confirmation study by Avid. The study revealed that PET scans using F18 were positively confirmed at autopsy by traditional immunohistochemical techniques and the data suggested that F18 retention correlates well with actual beta-amyloid deposits in AD brain2. Furthermore, brain scans of participants who where were not diagnosed with AD were negative for F18 binding2.
However, on January 20, 2011, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee decided (13 to 3) that it could not approve Avid/Eli Lilly’s New Drug Application for Amyvid in its current form. The biggest concern for the FDA was the consistency between the readers, and therefore the interpretation, of the scans. However, the committee voted unanimously to reconsider the application for approval if the company could strengthen its case that Amyvid scans could be read consistently from one reader to another, in a previously acquired set of scans resembling the intended patient group and using the actual reading method that is to be applied in clinical settings. In general, the FDA follows the recommendation of its advisory committees.
What is next for Amyvid?
Avid had anticipated concern about the reads and have developed a binary read method that uses black-and-white versions of the scans together with a training protocol for routine clinical use. The FDA encouraged Avid to continue with this work and collaborate with professional organizations (Society for Nuclear Medicine, American College of Radiology) to develop education and training for amyloid imaging. Representatives from such organizations were present for the FDA’s decision and testified that they would be willing to help develop such training programs.
How long of a delay will there be for use of Amyvid in clinical practice? A few months? A few years? It is not certain. Luckily, the FDA ruling does not affect the use of amyloid imaging agents, such as Amyvid, PIB and others, in research studies and therapeutic trials. This is some good news for scientists and clinicians around the world who believe that amyloid imaging is a key piece, and perhaps the greatest advance in AD research as a whole, in recent years.
More about the author, Charlene Supnet, Ph.D.
Journal of Nuclear Medicine. 2010. 51(6): 913-920.
Journal of the American Medical Association. 2011. 305(3):275-83.