The Food and Drug Administration has approved a new amyloid imaging agent, which, during a positron emission tomography scan, produces colored images of the brain plaques that are the diagnostic hallmark of Alzheimer’s disease.
Flutemetamol F 18 injection is indicated as a diagnostic aid only. A positive scan indicates that there is some amyloid in the brain but doesn’t establish a diagnosis. A negative scan means there is little or no amyloid present, which means that Alzheimer’s disease (AD) is probably not the cause of cognitive symptoms. The scans can be read only by clinicians who undergo a specialized training program, according to the FDA announcement.
GE Health care will market flutemetamol as Vizamyl. The drug is manufactured for GE Healthcare by Medi-Physics Inc.
"Vizamyl represents a new and important option to augment the current methods we have available to evaluate patients with symptoms of Alzheimer’s disease," Dr. William E. Klunk, codirector of the Alzheimer Disease Research Center at the University of Pittsburgh, said in a GE Healthcare statement. "The ability to detect or exclude the presence of beta amyloid plaques in the brain may help physicians make more accurate assessments of patients with suspected cognitive disorders, including AD."
Dr. Klunk was a member of the team that invented Pittsburg Compound B (PiB), the first radioligand used to examine amyloid plaques in living brains. Although PiB was a breakthrough research tool, its extremely short half-life (20 minutes) severely limits its usefulness as a diagnostic tool. Like other radioligands containing fluorine-18, flutemetamol has a 2-hour half-life.
Dr. Richard J. Caselli
Flutemetamol was approved based on data from two pivotal phase III studies involving 384 patients who had a wide range of cognitive function. All received the drug by intravenous infusion and underwent positron emission tomography (PET) scanning. It detected beta amyloid with a median sensitivity of 75%-100% and specificity of 99%-100%. A similar accuracy also was found in a subset of subjects who underwent autopsy. There was a high level of agreement among trained readers who assessed the scans visually.
In safety studies, flutemetamol was generally well tolerated. The most common adverse reactions reported in clinical trials were flushing, increased blood pressure, headache, nausea, and dizziness; these occurred at rates of 2% or less. One subject had a serious hypersensitivity reaction (flushing, dyspnea, and chest pressure) within minutes of administration and recovered with treatment.
Flutemetamol is the second fluorine-18 radioligand to be licensed. Florbetapir (Amyvid) was approved in April 2012. In contrast to flutemetamol color scans, images produced with florbetapir are in black and white. They can be color enhanced, but prescribing information states that they must be read in black and white.
In August 2012, the FDA reprimanded Eli Lilly, the maker of florbetapir, for using "misleading," color-enhanced scans on its Amyvid home page. Physicians who read the scans must pass a specific training class, which uses the black and white images. Using color images suggested that colorized scans can be used for reading – something FDA said could increase the chance of misinterpretation.
Lilly immediately removed the color images and replaced them with the more representative black and white images, which are currently seen.
With the rise of Alzheimer’s disease – and no cure or effective preventive strategy in sight – researchers and clinicians are homing in on early detection as the best way to get a handle on the disease. Imaging agents are key to this effort, but despite their proven ability to detect even small amounts of amyloid, these scans are not yet covered by public insurance.
The Centers for Medicare and Medicaid Services announced in July that it would cover only one scan per person, and then only if the scan was done in the context of a clinical study. That decision covers all of the amyloid imaging agents and hamstrings the clinical utility of PET scanning, said Dr. Richard J. Caselli, director of the Clinical Core of the Arizona Alzheimer’s Disease Center at the Mayo Clinic, Scottsdale, Ariz.
"Current CMS policy with regard to reimbursement basically restricts payment to a single amyloid PET scan that is required for entry into a research trial. Lack of reimbursement generally has been a limiting factor in the performance of these scans for routine diagnostic purposes," he said in an interview.
Dr. Klunk was an investigator on one of the phase III trials of flutemetamol and is a consultant to GE Healthcare. Dr. Caselli has no financial disclosures.
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