Editor’s note (July 12, 2021): On July 8, 2021, the FDA updated prescribing information for Aduhelm (aducanumab). The drug now is approved for people with mild cognitive impairment or mild Alzheimer’s dementia. These groups tested the drug for safety and effectiveness in clinical trials.
A new Alzheimer’s drug — Aduhelm (aducanumab) — has been in the news a lot. It’s the first Alzheimer’s disease (AD) therapy since 2003 and the first that targets the disease process, rather than only symptoms.
While there are differing opinions about the drug’s approval, many people and families with Alzheimer’s disease (as well as those with Parkinson’s) wonder what it could mean for their care and daily life.
For answers to these questions and more, we spoke with Melissa Armstrong, MD, MSc, associate professor and director at the Dorothy Mangurian Clinical-Research Headquarters for Lewy Body Dementia at the University of Florida’s Department of Neurology.
The Michael J. Fox Foundation (MJFF): Let’s make sure we’re all on the same page. Tell us a little bit about aducanumab.
Melissa Armstrong (MA): There are proteins that clump in the brains of people with Alzheimer’s, Parkinson’s and other brain diseases. One protein that clumps in Alzheimer’s is amyloid. The hope is that if you reduce amyloid clumps, you can slow the progression of disease.
In clinical trials, aducanumab reduced amyloid clumps seen on specialized brain scans. But it’s not clear that decreasing these clumps helped memory and thinking. In a small group of volunteers with early (mild) Alzheimer disease who got the highest dose of aducanumab, there was a slight improvement on memory and thinking tests. But it’s not clear if or how this translates to improvement in daily life.
Because aducanumab was approved based on brain scan changes (rather than memory and thinking improvements), the U.S. Food and Drug Administration (FDA) gave the drug conditional approval. This means that Biogen, the maker of aducanumab, now has to do a follow-up study to see if memory and thinking improve when brain scans improve.
MJFF: I’m sure you, like many doctors, are getting a lot of questions about aducanumab. What are you telling patients and families?
MA: There is a lot doctors have to figure out before they may be able to offer aducanumab more broadly. The therapy is a monthly infusion (it’s given through an IV), not a pill you can pick up from the pharmacy. So there are logistics to decide, including:
- Who will prescribe aducanumab?
To prescribe this drug, doctors need the right expertise, testing equipment, staff and other office support. It may be that only Alzheimer’s and dementia specialists are able to prescribe, for example. (And, unfortunately, there is a shortage of these experts which can limit access and lead to long waiting lists.)
- Who may be a good candidate?
The FDA approved aducanumab for people with Alzheimer’s. But the studies included only people with mild cognitive impairment (MCI) due to Alzheimer’s or early Alzheimer’s. Many doctors may feel that aducanumab is best used only in people with these early changes.
- What tests may be required?
All aducanumab study participants had specialized brain scans, called PET, that showed amyloid brain clumps. Prior to starting aducanumab, patients may need this type of testing. (Unfortunately, the scan is not currently covered by insurance and is expensive.) An alternative may be a spinal tap, or lumbar puncture, which tests fluid around the spinal cord for amyloid.
- A person also will need several MRI brain scans while taking aducanumab. These look for side effects, which include brain inflammation or bleeding. Almost 40 percent of people in clinical trials experienced one of these side effects, but most of them did not have symptoms.
- How long should treatment continue?
We’re not quite sure. In studies, participants received monthly infusions of aducanumab for 18 months. So doctors are wondering, do we give it for 12 or 18 months and then stop if the brain scan improves? Then do regular brain scans to see if amyloid comes back? This hasn’t been studied, so we don’t really know. Hopefully more research will provide more insight. But in the meantime, some of these decisions may be guided by Medicare and insurance protocols for drug coverage.
- Will insurance cover it?
We’re not sure how much of the costs Medicare and other insurers will cover. (There’s the cost of the medication, but also additional costs for brain scans, doctor appointments, and more.) We’re also not sure who payers will cover — all people with Alzheimer’s or only those with early stages of disease, like those in the studies? We don’t know when Medicare and insurers will make these decisions, but it could be months or more.
MJFF: Some — not all — people with Parkinson’s experience significant thinking and memory changes. What should they and their families know about aducanumab?
MA: Parkinson’s disease itself can cause dementia. (This doesn’t happen in everyone with Parkinson’s.) In these cases, it’s not Alzheimer’s and it’s not linked to amyloid. So we wouldn’t expect aducanumab to help because aducanumab targets amyloid protein.
In Parkinson’s, the trouble-making protein is alpha-synuclein. Researchers believe clumps of this protein may contribute to Parkinson’s. They also may contribute to thinking and memory changes in people who have those symptoms. Clinical trials now are testing more than a dozen different therapies against alpha-synuclein with the hope of clearing this protein to slow or stop disease.
It’s true that some people with Parkinson’s also have amyloid. But clearing amyloid without clearing alpha-synuclein, using a new therapy like aducanumab for example, may not help much. (And comes with possible side effects, too.)
In the future, for people with different kinds of brain protein clumps, doctors might be able to use multiple treatments, each targeting a different protein.
MJFF: Anything else we should know?
MA: We all really, really, really want new treatments for Alzheimer’s. It’s a huge unmet need. It’s still unmet, even with aducanumab. So I want to stress the importance of continued research for Alzheimer’s drugs. And the continued need for volunteers to participate in that research.
Like many have said, aducanumab is the beginning, not the end. We’re not sure if and how much aducanumab will help. And it’s unlikely to work in everyone with Alzheimer’s. If you or your loved one consider aducanumab, work with your doctor to get a good understanding of what the drug may or may not be able to do for you.
Get Cleveland Clinic’s answers to FAQs about aducanumab.
To learn what the aducanumab approval means for Parkinson’s research, read our blog and an op-ed by Ken Marek, MD, MJFF scientific advisor and principle investigator of The Parkinson’s Progression Markers Initiative study.