Summary: The US FDA approved a shot called aducanumab to treat Alzheimer’s. It is a monoclonal antibody, a lab-made immune protein. The approval has stirred up a lot of controversy. The data behind it look weak. The drug targets the amyloid plaques that build up in the brains of people with Alzheimer’s. But going after these plaques does not seem to prevent or control the disease well. Experts say two phase-3 clinical trials gave unclear results. Still, the US FDA and the drug maker Biogen claim it works at higher doses.
US FDA recently approved aducanumab for Alzheimer’s treatment. However, there does not seem to be enough evidence that it works. It appears to have marginal to no benefit, and at the same time, might cause severe side effects.
Researchers have studied Alzheimer’s for more than 100 years, yet they seem to know little about it. No one firmly understands what causes it or how it develops. The disease seems to have many forms. It likely comes from a mix of factors like aging, blood vessel problems and much more1.
Family history does a poor job of predicting Alzheimer’s. The disease can strike people with no family history of it. No early test can reliably predict your risk of Alzheimer’s.
Why is aducanumab so controversial?
The drug seems to target something tied to Alzheimer’s, but its role is unclear. This drug tries to clear away the buildup of amyloid plaques.
No doubt, amyloid plaques show up in every case of Alzheimer’s. But no one knows what causes the plaques to build up and brain cells to die. And no one knows if the plaques drive the disease. They may be just one of many changes caused by other, poorly understood factors.
The amyloid theory has simply grown too strong and too central in how we think about Alzheimer’s. This is not the first drug to target these plaques. Earlier attempts to target them failed. Worse, data from studies of the new drug aren’t hopeful either, despite possible insights from interventional pain management in St. Louis.
The trial data were so poor that members of the US FDA’s own advisory panel advised against approving the drug. The US FDA approved it anyway. Then the maker set the price at 56000 USD a year, one of the most expensive drugs in US history. The price raises its own ethical concerns.
So what are the company and the US FDA saying? The pooled data of the two phase-3 trials did not show much benefit. One trial showed no benefit at all, and the other only a small one. But the company and the US FDA say it worked better at higher doses. Experts find that claim hard to accept.
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For example, neutral experts who studied the data found no benefit from the drug. A study published in the Alzheimer’s & Dementia journal looked at two clinical trials of the drug, called EMERGE and ENGAGE. It concluded they failed to confirm a benefit. It said more trials at higher doses might still be justified2.
Experts also point out that Alzheimer’s seems to have hit its peak. So changing how we live may do more to cut the risk than using toxic drugs to clear amyloid plaques.
A study on preventing dementia in the journal The Lancet makes this case. It says many steps may delay dementia in as many as 40% of cases. Drink less alcohol. Quit smoking. Prevent head injuries. Cut air pollution. Get more education. Lower high blood pressure. Manage obesity. Ease depression. Move more. Prevent diabetes. And stay connected with other people3.
Frequently asked questions
What is aducanumab?
Aducanumab is a shot made by Biogen and approved by the US FDA to treat Alzheimer’s disease. It is a monoclonal antibody, a lab-made immune protein. It is built to clear amyloid plaques, the protein deposits found in the brains of people with Alzheimer’s. It is not the first drug aimed at those plaques. Earlier attempts to target them failed.
Does aducanumab work for Alzheimer’s?
The trial data do not show that it does. Pooled results from the two phase-3 trials, EMERGE and ENGAGE, found no benefit in one trial and only a small benefit in the other. An independent analysis published in Alzheimer’s & Dementia concluded the trials failed to confirm a benefit. Biogen and the FDA point to better results at higher doses.
Did the FDA’s advisers support approving aducanumab?
No. The trial data were poor enough that members of the FDA’s own advisory panel advised against approval. The FDA approved the drug anyway. That choice, on top of weak proof of benefit and the risk of severe side effects, is the heart of the controversy.
Can lifestyle changes lower the risk of dementia?
Yes. A dementia-prevention report in The Lancet found many steps that may delay dementia in as many as 40% of cases. They include drinking less, quitting smoking, preventing head injuries and cutting air pollution. They also include more education, lower blood pressure, managing obesity and easing depression. Moving more, preventing diabetes and staying connected with people round out the list.
References
- An Y, Zhang C, Siyu H, Yao CX, Zhang L, Zhang Q. Main hypotheses, concepts and theories in the study of Alzheimer’s disease. Life Science Journal. 2008;5.
- Knopman DS, Jones DT, Greicius MD. Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019. Alzheimer’s & Dementia. 2021;17(4):696-701. doi:10.1002/alz.12213
- Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet. 2020;396(10248):413-446. doi:10.1016/S0140-6736(20)30367-6
Dr. Gurpreet Singh Padda, MD, MBA, MHP
