The Food and Drug Administration’s approval of the first amyloid plaque-imaging agent, florbetapir F18, may usher in a “new age” in the diagnosis of Alzheimer’s disease, according to Dr. Daniel Skovronsky.

“We are entering a new age in which we can evaluate patients [with cognitive decline] based on the molecular pathology in the brain,” rather than on symptoms alone, Dr. Skovronsky, president of Avid Radiopharmaceuticals, said in a press briefing on April 9. “We hope this will also lead to the generation of therapies that don’t only target the symptoms but also the molecular pathology of the disease. It’s our long-term vision that through early detection and interventions, someday we can make Alzheimer’s a preventable disease.”

Florbetapir (Amyvid), which was approved on April 6, binds to beta-amyloid plaques in the brain, the diagnostic hallmark of Alzheimer’s. Until now, clinicians have based the diagnosis on symptoms and cognitive testing, although they have been estimated to misdiagnose about a fifth of patients with probable Alzheimer’s based on definitive diagnosis established at autopsy. A florbetapir scan can now reliably exclude a diagnosis of Alzheimer’s, Dr. Skovronsky said.

“A positive scan does not mean the patients have Alzheimer’s, since neuritic plaques can be seen in other diseases and are also sometimes present in cognitively normal people as they age,” he noted.

The scans should be used in conjunction with clinical findings to help shape a patient’s treatment, he added.

But the ability to pinpoint amyloid status may create more problems for a population already struggling with a difficult diagnosis, according to the Alzheimer’s Association. Although the group supports the approval, it called florbetapir’s approval a “double-edged sword,” and expressed concerns about how florbetapir could be used.

“On the one hand … this product will expand the clinical and research opportunities for amyloid imaging by making this brain imaging tool more widely available to the field. On the other hand, the fact that all of the potential uses of this product are not crystal clear tempers our enthusiasm. Again, additional research is needed to clarify the role of florbetapir-PET imaging in Alzheimer’s,” the association said.

The product could be used to exploit patients as well. “The Alzheimer’s Association is also concerned about the possibility of less-than-scrupulous operators offering imaging services and making unrealistic promises about the value of florbetapir imaging to sometimes vulnerable and worried individuals. As such, we recommend that people get access to this test only in the context of a complete evaluation of medical/neurological status and with appropriate expert consultation.”

Last year, an FDA advisory panel voted against immediate approval of florbetapir because of concerns about interreader variability and the lack of a single reading technique. Since then, Avid Radiopharmaceuticals and its parent company, Eli Lilly, have created a reader training tool, which has been shown to improve scan interpretation, Dr. Skovronsky said. The training program will be available online and in person to clinicians who will be interpreting the scans.

He said Lilly did not compare inter-reader reproducibility before and after the training program. But after the training, readers who re-evaluated scans in the three pivotal approval trials agreed on the results 83% of the time, according to a Lilly spokesperson.

The company compared online and in-person training strategies in one of the three trials, which assessed positive scans in relation to a pathologic diagnosis of Alzheimer’s. Scans evaluated by readers trained in person showed a median sensitivity of 92% and a specificity of 95%. Those evaluated by readers trained online were slightly less accurate, with a median 82% sensitivity and 95% specificity. The company did not say whether these differences were statistically significant or clinically meaningful.

Florbetapir is also playing a role in research. The lack of a reliable biomarker of Alzheimer’s disease progression has hampered research into disease-modifying therapies. Imaging compounds, including florbetapir, are being investigated for their ability to provide visual markers that could show any response to drugs designed to affect beta-amyloid plaque levels.