New Diagnostic Tool Approved for Evaluation of Dementia Patients

Anew diagnostic tool for the evaluation of patients with dementia has received FDA approval. Amyvid (Florbetapir F 18 Injection, Eli Lilly and Company/Avid Radiopharmaceuticals, Inc.), is a radioactive diagnostic agent indicated for brain imaging of beta-amyloid plaques in patients with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline. Amyvid binds to amyloid plaques, a hallmark characteristic of Alzheimer’s disease, and is detected using PET scan images of the brain.

A negative Amyvid scan indicates sparse to no amyloid plaques are currently present, which is inconsistent with a neuropathological diagnosis of Alzheimer’s disease and reduces the likelihood that a patient’s cognitive impairment is due to Alzheimer’s disease. A positive Amyvid scan indicates moderate to frequent amyloid plaques are present; this amount of amyloid plaque is present in patients with Alzheimer’s disease, but may also be present in patients with other types of neurologic conditions and in older people with normal cognition.

The companies behind Amyvid point out that it’s important to note that Amyvid is an adjunct to other diagnostic evaluations, notably clinical evaluations. A positive Amyvid scan does not establish a diagnosis of Alzheimer’s disease or other cognitive disorder. Additionally, the safety and effectiveness of Amyvid have not been established for predicting development of dementia or other neurologic condition, or monitoring responses to therapies.

Nonetheless, there is generally positive reaction to the agent’s approval. “Up until now the only other agent available to measure amyloid in the brain and available in a limited number of research centers is Pittsburgh Compound B,” said Ronald Devere MD, FAAN, Director of the Alzheimer’s Disease and Memory Disorders Center, Austin, TX, who was not involved in trials of the diagnostic. “This compound has required the use of a cyclotron to produce amyloid images. Amyvid appears to be the first agent that is now approved by the FDA and can be used with a PET Scanner without the need for complex equipment. It will likely be available for use in all diagnostic facilities with PET Scanners.”

Amyvid will be helpful in establishing the diagnosis of Alzheimer’s disease in some patients, which has a large amount of Beta amyloid, versus other causes of dementia, such as frontal lobe or vascular dementia, and other types which likely have much lower levels of Beta amyloid, according to Dr. Devere. “It may also be very helpful in determining which patients with MCI will likely go on to develop future Alzheimer’s dementia,” he said.

Dr. Devere mentioned an ongoing prospective study following younger individuals with a family history of AD and those without a history in the presymptomatic phase that is tracking which changes in cognitive testing, spinal fluid analysis for beta amyloid and tau, and amyloid imaging changes occur in those destined and develop AD. “This along with other studies will determine how much and where amyloid is located in the brain and when it is diagnostic of AD versus other cause of dementia,” he said.

Amyvid was evaluated in three clinical studies that examined images from healthy adult patients as well as patients with a range of cognitive deficits, including some terminally ill patients who had agreed to participate in a postmortem brain donation program, according to the companies. Based on the results of study one, measurements of postmortem cortical amyloid burden correlated with median Amyvid scores (r=0.78; P<0.0001). In the second study, using the majority interpretation of five readers, Amyvid PET showed 96 percent sensitivity and 100 percent specificity in patients who received an Amyvid PET scan within one year of death. Across all readers and all autopsied patients, Amyvid PET demonstrated median sensitivity of 92 percent (range 69 percent to 95 percent) and specificity of 95 percent (range 90 percent to 100 percent) for readers trained in person (study two), and median sensitivity of 82 percent (range 69 percent to 92 percent) and specificity of 95 percent (range 90 percent to 95 percent) for readers trained using an electronic media-based training (study three). Additionally, inter-reader reproducibility analysis for all images in study three showed an overall Fleiss’ kappa statistic of 0.83 (95 percent CI: 0.78 to 0.88).

Because Amyvid loses over half of its radioactivity every two hours, Amyvid must be distributed directly from a radiopharmacy to the imaging centers where it will be administered within several hours. Beginning in June, a limited number of radiopharmacies will begin distributing Amyvid with the goal to gradually increase the product’s availability.

The companies recommend Amyvid images be interpreted only by readers who have successfully completed Amyvid reader training. Lilly says it has worked collaboratively with the FDA and nuclear medicine experts to identify the appropriate ways to support accurate and consistent interpretation of Amyvid scans by imaging physicians. These efforts resulted in the development and validation by Lilly of both an online and in-person reader training program for physicians using Amyvid. Errors may occur in the estimation of plaque density during image interpretation, the companies said.