Statement on Aducanumab
James E.C. Walker Memory Assessment Program, UConn Center on Aging
Division of Geriatrics, Department of Medicine
Department of Neurology
Division of Geriatric Psychiatry and Behavioral Health, Department of Psychiatry
University of Connecticut School of Medicine
On June 7, 2021, the U.S. Food and Drug Administration (FDA) approved aducanumab (Aduhelm®) for the treatment of mild cognitive impairment (MCI) and mild Alzheimer’s disease. While this is exciting news for patients with Alzheimer’s disease and their families, there are many questions about this new treatment.
What is aducanumab and how does it work?
Aducanumab is an antibody (biological drug) given by vein (IV) as an infusion treatment every 4 weeks, usually in an outpatient infusion center. Each infusion takes about an hour. There is no pill form of this medication. It targets a protein called amyloid-beta that accumulates in the brains of people with Alzheimer’s disease. Amyloid-beta protein forms deposits called “plaques” that may contribute to cognitive decline. Aducanumab helps the immune system remove the amyloid-beta deposits from the brain, which may slow disease progression.
Is this drug a cure for Alzheimer’s disease?
No. Aducanumab can’t reverse the damage already caused by Alzheimer’s disease and does not completely stop disease progression. It’s the first approved disease-modifying drug that appears in some studies to slow the progression of Alzheimer’s disease.
Who should or should not receive aducanumab?
Aducanumab was approved only for the treatment of Alzheimer’s disease, not for any other conditions that cause dementia. Patients with cognitive impairment due to other causes, such as vascular dementia, will not benefit from this treatment. A diagnosis of Alzheimer’s disease should be confirmed by physicians with expertise in treating dementia, using tests that show abnormal levels of amyloid or tau brain proteins. This can be done with a specialized brain amyloid PET (positron emission tomography) imaging scan or a lumbar puncture (spinal tap). A blood test for Alzheimer’s disease proteins is being developed but is not yet available.
The FDA did not initially specify which patients with Alzheimer’s disease are appropriate for this treatment. Aducanumab has so far been tested only in patients with MCI or early-stage Alzheimer’s dementia, who tested positive for brain amyloid. It may not be appropriate for those with later stages of dementia. After feedback from the scientific community, the FDA revised its approval to only those patients with MCI or early Alzheimer’s disease.
Whether this medicine is appropriate for you or your family member depends on many individual factors. Physicians at the University of Connecticut School of Medicine with expertise in the diagnosis and treatment of Alzheimer’s disease are available for consultation and can discuss this possibility with you.
What are the adverse effects of aducanumab?
In clinical trials, 21% of patients experienced headaches, while less than 10% experienced confusion or delirium. About 35% of patients in the clinical trial developed changes on their MRI scans within the first 4 months of treatment. These imaging changes are called Amyloid-Related Imaging Abnormalities (ARIA), consisting of brain swelling, sometimes with small amounts of bleeding. Fortunately, only about 30% of people who develop ARIA experience symptoms. In addition to the headaches and confusion, adverse effects can include vomiting, nausea, dizziness, tremor, and vision changes. The imaging changes and symptoms most often resolved over time with close monitoring but sometimes required stopping the drug. The potential risks and benefits of aducanumab must be thoroughly considered for each patient.
What other testing is needed?
Before considering treatment for Alzheimer’s disease, evaluation by an Alzheimer’s disease specialist is critical. The diagnosis requires a careful clinical examination, cognitive testing, blood tests, and brain imaging. These tests help rule out other conditions such as vitamin deficiency or stroke that may cause cognitive impairment. As noted above, an amyloid PET scan or lumbar puncture may be required. The FDA label requires a brain MRI within one year prior to initiating treatment and brain MRIs prior to the 7th and 12th infusions. More imaging tests may be needed during treatment to monitor for adverse reactions.
When will the drug be available? What will it cost?
It may take several months before aducanumab is made available for patients. Biogen, the company that makes aducanumab, has proposed a cost of $56,000 per year. However, there will be additional costs associated with the MRI or PET scans, lumbar puncture and blood tests, and the costs of the infusion. We don’t know how insurance companies will handle authorization for this medication.
Why is this drug controversial?
Aducanumab was evaluated in two large studies of mildly impaired patients with Alzheimer’s disease. In one of the studies, high doses of aducanumab slowed the rate of cognitive decline, but this trial was stopped early when the long-term benefit was unclear. Additionally, the slightly reduced rate of cognitive decline did not correlate with any noticeable functional improvement. It did not reduce cognitive decline in the second study. In both studies, aducanumab reduced the number of beta-amyloid plaques. Reducing the amount of beta-amyloid plaques may reduce the rate of cognitive decline, but this has not been proven.
The FDA advisory committee evaluating the drug felt that there was not sufficient evidence of clinical benefit to warrant approval. However, the FDA approved the medication based on its ability to remove amyloid since there are no other approved disease-modifying treatments for Alzheimer’s disease. Whether the drug is effective in slowing cognitive decline remains unclear, even in the mildly affected patients who were tested, and we don’t know whether it will help patients with advanced disease.
Given the potentially serious side effects, the risk vs. benefit for this medication in the broad population of Alzheimer’s patients is unknown. As a result, the FDA has required Biogen to conduct another study after the drug is released. Several medical centers have stated that they will not prescribe the drug.
Will UConn Health physicians prescribe aducanumab?
The neurologists, geriatricians, and geriatric psychiatrists who treat Alzheimer’s disease at UConn Health are carefully weighing the evidence to determine whether this medication is beneficial and who it is most likely to help. We may be involved in the phase 4 clinical trial that will provide additional information on the safety and effectiveness of aducanumab. As more information becomes available, we will inform those eligible for the drug and may recommend participation in the trial so we can be more certain in the future about the potential risks and benefits.
Can I continue taking medicines like donepezil (Aricept®) or memantine (Namenda®) for Alzheimer’s disease while receiving aducanumab?
Yes, there is no interaction between these treatments and aducanumab, so patients may continue their current medications.
Where can I find more information?