MIND Center experts discuss promise, pitfalls of new Alzheimer’s drug
Published on Thursday, July 1, 2021
By: Karen Bascom
For the first time in nearly 20 years, Alzheimer’s disease patients, their caregivers and their physicians have a new tool to help slow the effects of this devastating disease.
The U.S. Food and Drug Administration approved Aduhelm, also known by the generic name aducanumab (add-you-KAN-oo-mab), on June 7. It’s the first new medication indicated for Alzheimer’s since 2003.
However, there are plenty of questions and concerns surrounding the drug. Experts at The MIND (Memory Impairment and Neurodegenerative Dementia) Center at the University of Mississippi Medical Center, a leader in research and clinical care for Alzheimer’s disease and dementia, discuss aducanumab.
“While we have had Alzheimer’s drugs that can improve memory, we previously did not have anything that could slow the progression of the disease,” said Dr. Juebin Huang, UMMC associate professor of neurology and director of The MIND Center’s Neuro-Clinical Core.
Huang says that the two Phase 3 trials for aducanumab had different results. After including additional data collected in the study, one trial showed that a higher dose of the drug slowed progression of Alzheimer’s disease symptoms by about 22 percent compared to placebo, while the other did not.
“So, the drug shows some evidence of benefit, but it’s not consistent,” Huang said.
Furthermore, the trials were initially stopped early because of futility, said Dr. Kim Tarver, assistant professor of medicine and director of The MIND Center’s clinical services. Because of that, “The move was surprising to a lot of us,” she said.
Aducanumab is a monoclonal antibody (MAB), a laboratory-made protein that helps the body recognize and break down harmful substances. While this is the first MAB-type drug for Alzheimer’s disease, doctors already use other kinds of MABs to treat autoimmune diseases, cancers, and, more recently, COVID-19.
“This is a big step for Alzheimer’s disease treatment. It is a new class of medication that targets the disease processes,” Huang said.
The drug targets beta-amyloid plaques, a build-up of proteins in the brain. Scientists think these may be involved in the symptoms of Alzheimer’s disease, although there is still some uncertainty about the role they play.
“We don’t know if plaques are the problem [that leads to Alzheimer’s disease symptoms], or a side effect of the problem,” Tarver said.
In terms of side effects from aducanumab, Huang says that the clinical trials for the drug showed a significant risk for a side effect not found in other FDA-approved Alzheimer’s treatments: Amyloid related imaging abnormalities, or ARIA. This refers to swelling and small bleeds in the brain related to the antibody treatment. About one-third of patients in the trial experienced ARIA, but few had serious complications. However, Huang and Tarver say physicians and patients still need to watch for this potential side effect.
“As a neurologist, whenever I see that someone can develop swelling in the brain from a treatment, that’s a concern for me,” Huang said.
“We don’t have enough data to know if the benefits outweighs these potentially dangerous side effects,” Tarver said. That’s part of the reason why the FDA has asked aducanumab’s manufacturer to continue clinical trials for efficacy and long-term safety, she said.
Both doctors have each received calls from patients who are curious about aducanumab after seeing news reports and hearing about the concerns. As more information becomes available, they plan to use resources from the Alzheimer’s Association, American Academy of Neurology and other professional organizations to help guide these conversations and determine best practices which patients might receive the most benefit.
“If I had a relatively young patient with limited cardiovascular risk factors and mild cognitive impairment or early-onset Alzheimer’s disease, I might consider this treatment because they seem to be the most likely to benefit,” Tarver said.
As with most newly approved medications, aducanumab will not be available for prescription for several months. The manufacturer needs time to ramp up production. Health systems like UMMC need to ensure they have the plans and infrastructure in place to do pre-prescription screening, drug delivery and monitoring.
When it does become available, Huang said that taking aducanumab will be “more complicated than a daily pill.
“This medication is a monthly infusion, so a patient would need to go to an infusion center once a month to receive treatment,” he said.
Another concern is cost. Huang said that aducanumab’s sticker price – about $56,000 per year – is expensive but “not out of character,” for a new, specialized medication. However, receiving a prescription for this drug will require additional testing and monitoring that will carry their own costs.
“The first step is to try to prove that the patient has amyloid plaques. You can do that with an amyloid PET (positron emission tomography) scan, but that is expensive and not usually covered by Medicare,” Huang said. “A patient can also get a lumbar puncture to test levels of amyloid and other Alzheimer’s markers in their spinal fluid. That is a cheaper procedure, but it’s invasive.”
For now, Huang wants to set “realistic expectations” for patients and their families.
“Aducanumab is not a cure. It is not a magic pill,” he said. “In clinical trials, this drug did reduce the amount of amyloid plaque in the brain, but in terms of clinical benefit and how much it slows down cognitive decline, we are not very certain of that yet,” he said.
“I am as hopeful as anyone for something that will make a difference for patients. However, we need to be mindful of safety and reality,” Tarver added.
Despite the uncertainties, Huang says that the aducanumab approval could mark the start of a new era of innovation in Alzheimer’s disease research.
“I have some hope that other companies can use this approval as motivation to find better monoclonal antibodies, and that this stimulates research to continue so that we can find better medications and someday cures for Alzheimer’s disease,” he said.
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