On June 7, the Food and Drug Administration (FDA) approved the first new Alzheimer’s medication in 18 years. Significantly, it is the first approved treatment that’s designed to address the actual disease process and not just dementia symptoms. But aducanumab, which goes by the brand name Aduhelm, has sparked controversy among medical experts; both Republican and Democratic senators have called for hearings on the drug. Steele Taylor, MD, neurologist and co-director of the University of Vermont Medical Center’s Memory Program, sorts out the details.
What is Aducanumab?
Most simply put, Aducanumab is an antibody that targets the plaques typically seen on the brains of people with Alzheimer’s, known as amyloid beta plaques. It helps the immune system clear them away. The theory is that removing these plaques will improve cognitive function or at least slow the progression of the disease.
How is it different from other currently available Alzheimer’s drugs?
Before this, we’ve have had two classes of medications approved for Alzheimer’s disease that work by treating some of its cognitive symptoms, including problems with memory and thinking. The first was approved in 1993 and the most recent was approved in 2003. Aducanumab is the first that is supposed to modify the underlying disease process, rather than just treat the symptoms.
You caution that aducanumab is not a cure. Why?
The Phase 3 clinical trial [advanced, large scale studies] results did not show that by reducing the amyloid-protein plaques the drug improves cognition. They only showed a very slight slowing-down in the rate of progression of the disease.
What are some of the other challenges associated with aducanumab?
Aducanumab is an extremely resource-intensive treatment from start to finish. The medication must be administered intravenously through 18 infusions, one month apart, in an infusion center within a health care setting. The drug is also very costly: $56,000 per year.
Most of the nation’s nearly 6 million Alzheimer’s patients don’t undergo testing to confirm the presence of amyloid protein in their brain. But it makes sense that clinicians and/or insurance companies would want to know the amyloid status of a patient before potentially starting them on this therapy. That would involve either an expensive PET scan or somewhat invasive lumbar puncture to analyze the cerebral spinal fluid. It’s unclear how much of any of this will be covered by private insurance or Medicare, particularly with regard to amyloid PETE scans. Also, widescale testing for amyloid in patients with presumed Alzheimer’s disease could easily overwhelm the current capability to perform such testing, both in our facility and in health care systems nationwide.
What are the potential side effects?
The two most common – they occurred in about 35 percent of people during clinical trials – are brain swelling and mild bleeding within the brain. These side effects are not life-threatening, but we do need to know about them, and in many cases there are no symptoms. Because of that, MRI monitoring is needed. So, based on the FDA label, a patient would need an MRI before they start the aducanumab infusion, another one before the seventh infusion and another before the 12th infusion. Depending on what is found, therapy may need to be discontinued or suspended for a while – these side effects are generally reversible with time.
Are there still reasons to be hopeful about this drug?
I suspect that for many individuals who participated in the trial, the benefit was meaningful. And, that shouldn’t be discounted, especially because if you can prolong the earliest stages of the disease, that’s a lot of quality years that are potentially being preserved. Also, although aducanumab is certainly not a magic bullet, it may potentially be heralding us into a new era. If it does turn out that it actually delays the progression and keeps people in a milder stage of the disease for longer, then it does buy time for other therapies to come on the scene.
Will patients have access to aducanumab at UVM Medical Center?
I do think there are patients out there who would potentially benefit from this therapy, and so I’d like to be in a position to be able to make it available to them. But there are many discussions, logistics and protocols to be worked out first, so we do appreciate everyone’s patience.
Which patients with Alzheimer’s disease would be best suited for this drug?
Although the FDA initially approved the drug for anyone with Alzheimer’s, the patients enrolled in the clinical trials were in the early stage of the disease. And it’s likely that for this therapy to work, it needs to be started very early on in the disease process. Even though amyloid accumulation is a defining biomarker of Alzheimer’s disease, it sets into motion a series of other events that impair brain function, so it would be important to intervene before that happens.
The FDA subsequently revised the label, to restrict the use of this agent to those in the earliest clinical stages of the disease. This is more in line with the population of patients studied in the trials that lead to the approval of this therapy. In reality most Alzheimer’s treatment centers, including ours, were already planning to restrict the use to this population of patients, and we support the revision to the drug label.
Can you describe what the continuum of Alzheimer’s disease looks like?
If you were to take any given individual with Alzheimer’s disease and look back retrospectively, there would have been a time in which they had no symptoms, but there was already this accumulation of amyloid and tangles of another protein, tau, occurring in the brain. This asymptomatic period can last for five, 10, even 15 plus years. Next is the mild cognitive impairment stage where it’s clear to the person and/or to their family that there’s been some decline in cognition. Although there’s a decline in memory, they are still functional and able to live independently, perhaps with some strategies to help compensate for their deficits. Eventually, a person progresses to a point where they’re really no longer functionally independent. And that’s when we start to say they’re in a mild stage of Alzheimer’s dementia before they progress through moderate and severe stages.
What advice would you give to someone who’s worried they’re experiencing cognitive decline?
There’s very good evidence that implementing a combination of lifestyle interventions is effective at either preventing or delaying the onset of dementia. We recommend a combination of measures to promote good sleep quality; physical activity, including both aerobic and resistance exercise; and good cognitive activity, through both intellectual activity and social activity. Certain dietary strategies also seem to make a difference. The MIND diet has been shown to prevent cognitive decline after stroke and is also believed to be beneficial for brain health overall.
What does the future of Alzheimer’s treatment look like?
It’s unlikely that there will be a single cure to treat Alzheimer’s disease. What is more likely is that we’ll have a combination of therapies to have a more impactful overall benefit to individuals. Maybe, once that’s in place, we’ll enter into an era when we can screen individuals at a certain age to see if they might be eligible to initiate therapies, even in the preclinical stages. Aducanumab may help to accelerate this work, which is exciting.