The US Food and Drug Administration (FDA) has approved a third agent for imaging β-amyloid in the setting of Alzheimer's disease (AD), florbetaben F18 injection (Neuraceq, Piramal Imaging).
Florbetaben is indicated for positron emission tomography (PET) of the brain to estimate β-amyloid neuritic plaque density in adults with cognitive impairment who are being evaluated for AD and other causes of cognitive decline. It was recently also approved in Europe.
Two other PET imaging tracers, florbetapir (Amyvid, Eli Lilly and Company) and flutemetamol (Vizamyl, GE Healthcare), were approved previously by the FDA in 2012 and 2013, respectively.
As with these other imaging agents, a positive florbetaben scan does not establish a diagnosis of AD or any other cognitive disorder, but a negative scan indicating sparse to no amyloid plaques "is inconsistent with a neuropathological diagnosis of AD at the time of image acquisition; a negative scan result reduces the likelihood that a patient's cognitive impairment is due to AD," the company notes in a statement issued March 20.
"A positive Neuraceq scan indicates moderate to frequent amyloid neuritic plaques; neuropathological examination has shown this amount of amyloid neuritic plaque is present in patients with AD, but may also be present in patients with other types of neurologic conditions as well as older people with normal cognition."
This type of scan should be used as an adjunct to other diagnostic evaluations. The safety and effectiveness of this imaging agent has not been established, the statement notes, for predicting development of dementia or other neurologic conditions, or monitoring response to therapies.
At this time, the Centers for Medicare & Medicaid Services (CMS) will only cover β-amyloid PET scans for patients under Coverage with Evidence Development (CED) programs that aim to assess the utility of these scans to improve patient outcomes or advance patient treatment options, a decision that has disappointed some in the AD community.
Florbetaben images should be interpreted independently of a patient's clinical information, the statement adds. "Physicians should receive training prior to interpretation of Neuraceq images," the company notes. "Following training, image reading errors (especially false positive) may still occur. Additional interpretation errors may occur due to, but not limited to, motion artifacts or extensive brain atrophy."
Approval of the agent was based on safety data from 872 patients participating in global clinical trials, as well as 3 studies looking at images from adults with a range of cognitive function, including 205 end-of-life patients who agreed to participate in a post mortem brain donation program, the statement adds.
In that study, presented at the American Academy of Neurology annual meeting in 2012, images were analyzed from 82 patients with post mortem confirmation of the presence or absence of β-amyloid neuritic plaques. Correlation of the visual PET interpretation with post mortem histopathology in the 82 brains showed the agent accurately detected moderate to frequent plaques in the brain, the statement adds, "and is a useful tool to estimate the density of these plaques in life."
The most frequent adverse reactions during clinical trials were injection/application site erythema (1.7%), injection site irritation (1.2%), and injection site pain (3.9%).
Piramal Imaging acquired worldwide rights to the molecular imaging research and development portfolios of Bayer Pharma AG. The company recently partnered with IBA Molecular for manufacturing and distribution of florbetaben.