Eli Lilly and Company (NYSE: LLY) and Avid Radiopharmaceuticals, Inc., a wholly owned subsidiary of Lilly, today announced the U.S. Food and Drug Administration (FDA) approval of Amyvid™, 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.
It’s important to note that Amyvid is an adjunct to other diagnostic 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.
Alzheimer’s Disease is one of several possible causes of cognitive decline. Alzheimer’s Disease and other causes of cognitive impairment share many overlapping symptoms including memory, visuospatial ability, executive function, behavior and language deficiencies. Because a definitive diagnosis of Alzheimer’s Disease is usually determined upon autopsy, physicians rely on medical history, clinical examination and a variety of diagnostic tools when evaluating patients.
“It’s estimated that one in five patients clinically diagnosed with probable Alzheimer’s Disease during life do not end up having Alzheimer’s Disease pathology upon autopsy,” said Daniel Skovronsky, M.D., Ph.D., president and CEO of Avid, and global brand development leader for Amyvid at Lilly. “The approval of Amyvid offers physicians a tool that, in conjunction with other diagnostic evaluations, can provide information to help physicians evaluate their patients.”
Amyvid was evaluated in three clinical studies that examined images from healthy adult patients as well as patients with a range of cognitive disorders, including some terminally ill patients who had agreed to participate in a postmortem brain donation program. 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). The most common adverse reactions reported in clinical trials were headache (1.8 percent), musculoskeletal pain (0.8 percent), fatigue (0.6 percent), nausea (0.6 percent), anxiety (0.4 percent), back pain (0.4 percent), increased blood pressure (0.4 percent), claustrophobia (0.4 percent), feeling cold (0.4 percent), insomnia (0.4 percent) and neck pain (0.4 percent).
“Florbetapir gives patients with cognitive decline, their families and the physicians who treat them, more information about the amyloid plaques that may be found in their brain,” said R. Edward Coleman, M.D., professor of radiology, Duke University Medical Center. “This approval marks a great advancement in nuclear medicine practice, as it enables us to evaluate the presence or absence of moderate to frequent levels of amyloid plaques in a patient’s brain. In conjunction with other tests, florbetapir may help give physicians additional information when evaluating patients for the cause of their cognitive decline.”
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 be distributing Amyvid with the goal of making the product available in more areas as soon as possible.
“The approval of Amyvid exemplifies Lilly’s commitment to discovering and developing innovative products for many of the world’s unmet medical needs,” said Alex Azar, president, Lilly USA. “We are working hard with our manufacturing partners to increase production of Amyvid and will notify the community as it becomes available in more markets.”
Amyvid images should be interpreted only by readers who have successfully completed Amyvid reader training. Lilly 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.