Aducanumab: Should We Celebrate or Castigate?

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By now, you know that the FDA has approved the first new drug for the treatment of Alzheimer’s disease in eighteen years. And it’s the first drug on the market that targets a presumed cause of the disease, amyloid plaques in the brain. The current medications on the market treat the symptoms of the disease. This one aims to treat the disease.

You would think that this would make me jump for joy.

But the FDA’s approval is controversial for many reasons, and is making some researchers very angry.

And I feel stuck somewhere between the two extremes.

If this announcement had come at the very start of Harvey’s illness, I would have been cautiously optimistic and pushed for him to try it. If it had come out later in his disease process, I would not have. That’s because if the medication halts progression of the disease, I wouldn’t want him to have been stuck in the very difficult middle or late stages (more on this later in the post.)

If you’ve been following the news, what I’m about to outline is not new to you, but I thought it best to lay out the facts before I comment.

Aducanumab (trade name Aduhelm) was studied in two major trials, ENGAGE and EMERGE. In 2019, data from both of these studies showed no measurable effect. However, a few months later, by eliminating the results from participants who had received a lower dose of aducanumab in their statistics, the makers of the drug showed very slight improvements in cognition and function in the EMERGE study only.

Beyond the small improvements seen in the EMERGE study, the FDA also cited the “surrogate” endpoint of removal of amyloid plaque from the brains of study participants. That means that aducanumab did clear some of this abnormal protein buildup, as seen on PET scans. However, prior studies of similar drugs, monoclonal antibodies that remove amyloid, showed that while they did indeed remove amyloid, there was no clinical improvement in cognition or function. Why doesn’t removing amyloid have clear clinical effectiveness? We just don’t know.

And that brings me to side effects. Approximately 40% of participants experienced small bleeds in the brain and/or brain swelling. We’ve seen this in all of the prior drug studies of monoclonal antibodies against amyloid. Removing amyloid from the walls of blood vessels in the brain causes them to be leaky. Once the drug is stopped, the abnormalities repair themselves, and the drug can be restarted. Study participants were monitored with regularly scheduled MRIs to gauge this side effect.

And that brings me to cost. By now you’ve probably heard that the cost to deliver a year’s worth of Aduhelm via infusions is $56,000. That does not include the cost of an initial PET scan to diagnose Alzheimer’s disease, which is still considered investigational and usually not covered by health insurances. It does not include the cost of regularly scheduled MRIs, also not usually covered by insurances.

Other considerations:

Because Aduhelm specifically targets amyloid, it will not be prescribed for other forms of dementia such as Lewy body dementia, vascular dementia, or frontotemporal dementia.

The FDA approved Aduhelm for ALL patients diagnosed with Alzheimer’s disease, not just those in the very earliest stage of the disease as the study participants were. This means that if the drug actually does halt disease progression, patients and their families will need to decide if it’s better to stop the disease in its middle or late stages, or let the disease take its natural course. Too, our medical system is not equipped to handle the millions of patients who now qualify for this medication.

The advisory panel for the FDA’s neurological drugs, made up of non-biased researchers in the field, voted to not recommend approval for aducanumab. Ten members voted “No,” and one member voted “Uncertain.” There were no “Yes” votes. Three members resigned from the panel when the FDA announced its decision to approve. Why did the FDA override their expert panel? I have always respected the work that the FDA does to bring safe and effective medications to the market, a process that can be slow and cumbersome at times. This decision just smells fishy to me. Does the FDA feel like they need to approve this drug out of a desire to give hope to families affected by this disease? Have Alzheimer’s disease advocates pushed hard for its approval? Is there some outside pressure to approve ANYTHING new for Alzheimer’s disease? Is there political pressure? I don’t know. It’s just very odd and not good science.

Well, it sounds like I am not a fan of the FDA’s decision to fast track this expensive, potentially dangerous, not very effective drug. But there are some aspects of this saga that give me hope.

Research around monoclonal antibodies against amyloid have been ongoing for about 15 years, and although the end-results have not been promising, we now have better tools for diagnosing Alzheimer’s disease. We use to say that Alzheimer’s could only be diagnosed at autopsy. Now, we have PET scans that specifically signal amyloid plaques, lumbar punctures that detect amyloid in the spinal fluid, and a promising blood test in development that will detect amyloid. These biomarkers will allow physicians to diagnose Alzheimer’s much earlier, before symptoms even appear. And there is hope that we can develop biomarkers for other disease states.

We know now that amyloid plaques begin to build up decades before any symptoms. If we have a reliable blood test, conceivably, we will be able to screen for Alzheimer’s disease before it manifests itself. However, we would need an effective and safe therapy to offer those with a positive test.

This is where I see the future of research. If monoclonal antibodies against amyloid effectively and safely remove accumulated plaque from the brain, will doing so in subjects with an early positive blood test prevent or significantly decrease the likelihood of developing Alzheimer’s? That’s exciting to think about! I would enroll in such a study—just to advance our understanding.

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4 Responses

  1. Renee what a great article and I agree with you wholeheartedly. I would not stop the process in the middle or late stages. I’m hopeful there will be a test as you suggest for early screening, but again I would not recommend the use of this drug as it is now. It needs more research.
    Nick Nixon

    1. Thanks Nick. I am baffled why it was approved for all people living with Alzheimer’s.

  2. My husband was in a 2 year monoclonal antibody study at UAB.
    He was in the early stages and I do believe
    that it gave us more “time”.
    He is now in the middle stages and continues to decline.
    I definitely would not want him to have this drug at this stage or later.
    Why prolong our misery?

    1. Susan, I’m so glad you felt the drug gave you more time in the early stage! That’s very promising. I am very puzzled why it was approved for ALL persons with Alzheimer’s.