The American Academy of Neurology (AAN) has penned an “evidence-in-focus” report to help neurologists, patients, and their families digest the current evidence on the controversial Alzheimer’s drug aducanumab (Aduhelm).
The US Food and Drug Administration (FDA) approved the anti-amyloid agent to treat patients with early, symptomatic Alzheimer’s disease (AD) in June 2021. However, it did so against the advice of its own advisory panel and despite questions regarding the strength of the evidence supporting the drug’s efficacy and concerns about its high cost.
Currently, more than 6 million people in the United States have AD, with the number expected to grow significantly in the coming years.
As the first drug approved in the country to treat early AD, aducanumab is “of great interest to those facing this disease,” lead author Gregory S. Day, MD, Mayo Clinic, Jacksonville, Florida, and an AAN fellow, said in a news release.
“However, it is still unclear how much of a benefit the drug may provide and there are concerns about side effects. We hope this American Academy of Neurology evidence-in-focus article provides people with a better understanding of the evidence on aducanumab so far,” Day said.
The report was published online February 23 in Neurology.
For the article, the authors reviewed data from four clinical trials — one rated class I and three rated class II.
Results from the class I study showed that single doses of aducanumab up to 30 mg/kg was safe and well tolerated.
All three class II studies provided evidence that 3 mg/kg to 10 mg/kg aducanumab decreased amyloid plaques in the brain compared with placebo. However, it was unclear what effect the drug had on symptoms of AD.
“Efficacy data in the class II studies varied by dose and outcome, but aducanumab either had no effect on mean change on the Clinical Dementia Rating Sum-of-Boxes scores or resulted in less worsening (vs placebo) that was of uncertain clinical importance,” Day and colleagues write.
“Whether aducanumab will result in a clinically meaningful slowing of AD symptoms remains to be determined, as does the safety of aducanumab in clinical populations,” they add.
In clinical trials, roughly 40% of individuals treated with aducanumab developed adverse amyloid-related imaging abnormalities (ARIA) vs 10% of those receiving placebo.
ARIA typically occurred early during treatment and resolved within 4 to 12 weeks. About half (56%) of participants experiencing ARIA continued treatment. There was one fatal intracranial hemorrhage that was deemed to be related to aducanumab.
The most common adverse events were headache, urinary tract infection, and upper respiratory tract infection.
Aducanumab is given through monthly infusions. Since aducanumab it is a new drug, it’s unknown what to expect with long-term treatment, the authors note.
High Cost, Restricted Access
Cost is another issue. Treatment with aducanumab costs $28,000 per year, which does not include additional costs such as hospital visits for the infusion, clinic visits to monitor treatment, or cost of brain imaging to monitor for ARIA. Total costs of treatment could hit $75,000 a year, the researchers write.
Medicare recently announced plans to restrict access to aducanumab only to individuals with AD enrolled in clinical trials, significantly limiting the number of eligible patients, as reported by Medscape Medical News.
Day and colleagues say more research is needed regarding many aspects of aducanumab treatment, including whether the drug can slow AD progression, how often brain imaging is needed to monitor for brain swelling and bleeding, the optimal duration of treatment, and the criteria for when to discontinue use of the drug.
Until new research is available, they hope their evidence-in-focus report will increase understanding of the current data to help doctors, patients, and families discuss and make decisions on whether to pursue treatment with aducanumab.
The AAN previously published a position statement outlining ethical considerations and recommendations for informed consent regarding use of the drug.
The research was supported by the American Academy of Neurology. Day is supported by a career development grant from the National Institutes of Health, owns stock in ANI Pharmaceuticals, and serves as a topic editor for DynaMed, as a consultant for Parabon Nanolabs Inc, and as the clinical director of the Anti-NMDA Receptor Encephalitis Foundation. A complete list of author disclosures is available in the original article.
Neurology. Published online February 23, 2022. Abstract
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