Looking for answers about Alzheimer’s treatment Aduhelm (generic name aducanumab)? Here’s a primer on what it is, what it does, and more, according to experts.
What is Aduhelm?
Aduhelm is an experimental drug designed to use human antibodies to target toxic beta-amyloid proteins, hallmarks of Alzheimer’s. Following a rocky run of clinical trials, the generic aducanumab was approved for the treatment of Alzheimer’s by the FDA in June, 2021, making it the first disease-modifying Alzheimer’s drug to get FDA approval in 22 years.
The generic name for Aduhelm is aducanumab. Its ending, –mab, is shorthand for monoclonal antibodies, which are laboratory-made proteins that mimic the immune system’s defensive abilities. (Another –mab currently in the Alzheimer’s treatment pipeline is Eli Lilly’s investigational donanemab.) Currently developed by drugmakers Biogen and Eisai, the drug is administered via infusions.
How does Aduhelm work?
In the brains of people with Alzheimer’s, a protein called beta-amyloid is believed to propagate and clump into plaques, choking up the brain and leading to cell death and atrophy, and resulting in the loss of cognitive abilities. Aduhelm is designed to treat Alzheimer’s in people at the very early stages of the disease by removing the beta-amyloid protein build-up in their brains.
Dr. Stephen Salloway, a principal investigator of the aducanumab clinical trial and the director of Butler Hospital’s Memory and Aging Program, described the drug’s origin story in a recent Being Patient BrainTalk.
“The company [Neurimmune] that was developing it before Biogen looked at older people who lived a long life and either didn’t get Alzheimer’s or had a very slow form,” said Salloway, who in the past has consulted for Biogen and other pharmaceutical companies. “The company surveyed these people and looked for antibodies that might be retarding that Alzheimer’s process in the brain. The lead drug they found was aducanumab.”
According to Salloway, aducanumab enters the brain in very low concentrations and binds to the beta-amyloid plaques, then stimulating the immune system to help break up the plaques and remove them. “It looks like it does this pretty well — that it does lower the plaque build-up,” Salloway told Being Patient based on his experience with the drug’s clinical trials.
Where is Aduhelm available?
Following this approval, it would become available to patients within weeks.
However, many experts still feel the data around the drug’s effectiveness is lacking, so this FDA approval came with a condition: Biogen and Eisai are free to market Aduhelm, the FDA said, but they must do another large placebo-controlled trial. If Aduhelm proves ineffective after that trial, the FDA could remove the drug from the market.
There are dozens of other disease-modifying drugs designed to treat Alzheimer’s currently in the pipeline.
Who is Aduhelm for?
So far, aducanumab has been tested among patients with very early stage Alzheimer’s, who have only the mildest symptoms of the disease. It has not been tested in populations with later stages of Alzheimer’s. That said, the FDA’s label for the drug is quite broad, implying that it can be prescribed as a treatment to anyone with any stage of Alzheimer’s. Many experts think the label should be narrowed to the trial population — people with early Alzheimer’s only.
Has Aduhelm been effective in treating Alzheimer’s symptoms for participants in clinical trials?
Experts are divided on whether or not aducanumab is beneficial for patients with Alzheimer’s. In fact, after the drug’s approval, one member of the FDA’s panel of experts that initially advised the agency reject the drug resigned from his post.
While critics of the drug say that the two Phase 3 clinical trials of aducanumab — which were halted prematurely — fail to make a convincing case for approval, others believe its approval represents “the first incremental step in transforming the disease from an untreatable terminal illness to a manageable chronic disease.”
As Salloway put it: “There are investigators like myself who have had a lot of experience and view this [aducanumab] as beneficial to people, the opening of a new era for the treatment of Alzheimer’s. But you can also look the other way and say, ‘Geez, I’m not sure if the data is strong enough. Maybe we should wait and do more research.'”
“Emerging from a constant mental fog”
Trial participant and reporter Phil Gutis wrote for Being Patient, “I’ve learned through a longitudinal study PET scan that I no longer have any amyloid in my brain. The scan, taken about two years ago as part of the Aging Brain Cohort study at the Penn Memory Center, confirmed my growing inklings that aducanumab was indeed helping me. I began to feel like I was emerging from a constant mental fog … On the negative side, the memories that I’ve lost have not returned.”
“She declined very slowly”
Jim Taylor, husband of trial participant Geri Taylor, told Being Patient that before the aducanumab trial was interrupted, Geri had been on the drug for some three years, and during that time, her decline was very slow. “We really thought the drug was helping. Of course, there’s no way to know that, but her ability to maintain normal daily activities and live and take care of herself was really excellent. We traveled all the time and she managed all that well. During what I call the interregnum, the period when she wasn’t getting the medication, she started to decline more quickly. Now that she’s back on the drug, I kind of doubt it’s helpful. The benefit is really to get started as early as possible … She’s in the stage in which decline is noticeable, and it’s much more rapid.”
“Pretty stable over a pretty long period of time”
Salloway said that through his long and deep experience treating people with aducanumab over the course of the clinical trials, he has seen encouraging results. “Because the first trial lasted for a year against placebo and then everyone would continue on active medicine, we’ve had many people at our center who’ve been on aducanumab for more than five years and on active treatment,” he said. “The good news is that the majority of people that were on it actually stayed pretty stable over a pretty long period of time, which is not typical for Alzheimer’s because Alzheimer’s gets gradually worse. Preserving quality of life in early stages of Alzheimer’s is worth a lot, and families who at least had this stability really appreciate it.”
What are the side effects of Aduhelm?
The drug’s main known side effect is known as ARIA (amyloid-related imaging abnormalities), or a cerebral edema in which the tight endothelial junctions of the blood-brain barrier break down and subsequent accumulation of fluid.
“We found that when you remove the amyloid from the brain you also remove amyloid from blood vessels as well, especially in ApoE4 carriers, and that can cause a little bit of leakiness in the blood vessels, especially early in treatment, usually in the first six months,” Salloway told Being Patient. “Seventy percent of the time there are no symptoms, but there can be some mild symptoms. We monitor for that. We’ll see what the FDA says, but at least during the first year, I think people should have safety MRI scans every three months to monitor for that, and then sometimes we have to adjust the medicine. It almost always goes away on its own if we wait for it to clear.”
The FDA’s label, which experts say is surprisingly broad, recommends MRIs in advance of beginning treatment and MRIs prior to the 7th and 12th infusions — less frequently than they were administered during trials.
Additional reporting by Nicholas Chan