A new drug marketed as Aduhelm is the first the U.S. Food and Drug Administration (FDA) has approved to treat Alzheimer’s disease since 2003.
Novant Health behavioral neurologist Dr. Mark Pippenger got more than 20 calls from patients and their families the day it was announced. The Novant Health Memory Care - SouthPark doctor, a dementia specialist, cautions that there are more hurdles to cross and questions to answer before the drug can be administered.
Here’s what he told reporters about the potential benefits, risks and what’s still unknown about the drug created by Biogen.
How excited are you about this new drug?
I've been doing this for over 30 years, and we've had very little in the way of treatment successes for Alzheimer’s – the most common cause of dementia. We had a cluster of drugs introduced over 20 years ago, and those have been the mainstays of treatment.
In the meantime, we've been watching the research. Aduhelm is a monoclonal antibody – which activates the body's own immune system to clear out a harmful protein. Aduhelm clears out the amyloid protein, one of the abnormal proteins deposited in the brain with Alzheimer’s disease. It’s the clumping of that protein that disrupts cell function.
This is the first time we've had a treatment that's aimed at the disease process itself rather than the symptoms of the disease. So, I am excited.
But there is controversy about Aduhelm, right?
Yes. An independent review committee and some Alzheimer’s experts said there was not enough evidence to show the drug is effective. (Three FDA advisers resigned in protest over the decision.)
The drug is not home free by any means. But the FDA decided to approve it rather than wait for another study to be completed before giving the treatment because, if the drug has a benefit, we don't want to withhold it from people who could be helped.
Another concern: Aduhelm is tremendously expensive: $56,000 a year.
How is the drug administered?
It’s a monthly infusion. The patient has to come to the infusion center and have an infusion by vein.
Who is the ideal patient?
Someone with a diagnosis – by a specialist – of mild cognitive impairment, or mild dementia, due to Alzheimer's disease. Mild cognitive impairment is defined as having an impairment on memory tests, but not in daily functions.
It’s for people who have dementia that's very mild with a score on a common test we use, called the mini-mental state exam or MMSE, of over 24 out of 30.
To receive the drug, it will be necessary to prove that amyloid is present in the patient’s brain. And that can be done either with a PET scan or through spinal fluid biomarkers. Most people will prefer the PET scan, but I can tell you that a spinal tap is a very, very safe procedure. And a PET scan is tremendously more expensive than having the spinal fluid markers.
People who've had dementia for a long time or who have moderate or severe Alzheimer’s – unfortunately, this drug is not going to help them. We're pretty sure of that.
Our neurologists are ready to helpAct now
What will it look like for patients who go on this drug?
Their memory may not decline as fast. It may delay the time until the patient converts to a diagnosis of full-blown dementia.
A person on this treatment may retain for longer the ability to do things around the home – use the microwave or the remote for the TV. People should be able to do things for themselves a little longer. They might require less direct assistance over time. But again, these are people who are very mild to start with.
The company must conduct another study to prove that this drug is useful. And if that study – which could take a couple of years – doesn’t show benefit, then the FDA could withdraw their approval.
Do the benefits outweigh the risks?
ARIA is the side effect we’re most concerned about. It stands for amyloid-related imaging abnormalities. It can show up as swelling in the brain or fluid leaking out into the brain tissue.
It can also cause an increase in microhemorrhages. Patients typically don’t show symptoms of those, and we typically see more of those in people who have Alzheimer’s disease.
It occurred in close to 40% of patients treated in the studies but went away in 98% of them. Most of the patients did not have symptoms, and only 5% of patients had to drop out of the study due to this side effect.
ARIA sounds very scary, although it's actually kind of predicted. The amyloid protein not only gets deposited in the form of plaque, it's also deposited into the walls of blood vessels. When you remove that, it's like you're removing little chunks of the wall of blood vessels, and they become leaky.
That said, the majority of people who had ARIA didn’t have symptoms. And only a small percentage – something like 5% – had to stop treatment because of ARIA.
The side effects were generally easily managed, and most of them went away. I think it’s worth the risk based on what we know from the study. That's open to change depending on the new study and on our experience in the clinic, when we see what starts happening when we treat more people. Patients will need to be monitored carefully to watch for the development of side effects.
What are the signs of Alzheimer's disease?
It's basically significant memory trouble; having trouble keeping up with doctor's appointments, your bills, your medicines; difficulty in remembering what people tell you; being told you keep repeating yourself. Memory loss is the No. 1 thing. In a few people, it may be personality change. I always tell people: It doesn't hurt to get evaluated by a specialist.
When will this drug be available?
The company is planning to start shipping the drug within a few weeks. But other things have to happen first.
We'll have to get infusion centers ready. We'll also need the ability to do more diagnostic tests to confirm when amyloid is present. Those of us who operate within a hospital system have to wait on the pharmacy and therapeutics committees to approve the drug. And then Medicare must define who can prescribe it.
Anything else you want to add?
This is far from a cure, but it is a significant step, because it's a disease-modifying therapy.
This drug is, hopefully, the first in a series of drugs we'll start seeing because more is being invested in research. It’s sort of like the early days of cancer treatment. Chemotherapy had a lot of drawbacks at first. But look what's happened over the years.
Many of us are excited, because we think we're at a similar point in dementia and Alzheimer's disease – on the cusp of having more treatments. And this is the first. I think there’s reason for excitement. Hopefully, we can temper that with realistic expectations.