There's excitement — and controversy — surrounding Biogen's new Alzheimer's treatment Aduhelm, the first new Alzheimer's drug in nearly two decades.
One trial concluded it could delay cognitive decline in early phases of the disease by about 22%; another Phase 4 trial failed to show any benefit at all.
Both studies were stopped early when independent monitors concluded they were unlikely to show any benefits. But the Food and Drug Administration's approval does come with a condition: Biogen has to start a new trial, and the FDA could rescind the approval based on those results.
While there are treatments available that relieve symptoms of the disease, Biogen’s medication aims to get at the root cause. The company says Aduhelm, also known as aducanamab, reduces the amyloid plaques that build up in the brains of people with Alzheimer's disease.
It’s still unclear whether reducing plaque slows down the disease process.
U Penn Memory Center’s Dr. Jason Karlawish, an Alzheimer's physician, is reluctant to prescribe Aduhelm. He says he’ll educate patients and their families about the drug’s uncertainties, and if they want to take it, he’ll write a prescription.
“But I remain an unenthusiastic prescriber of this drug,” he says.
The idea of Aduhelm removing plaque from the brain to slow disease is “an attractive hypothesis,” he says. “But it remains a hypothesis. It remains one that needs to be studied.”
Karlawish shares objections with other Alzheimer’s specialists who say the studies weren't conclusive and that more research is necessary. The FDA’s independent advisory committee opposed the drug’s approval.
But Lenox Hill Hospital's Dr. Gayatri Devi, who has been treating patients with Alzheimer’s since 1994, says Aduhelm is “the most exciting drug that we have in our arsenal to date.” She supports the FDA’s approval and plans to include it in the treatment of some of her patients.
Clinical improvement, which was only shown in one of the trials, will vary depending on the severity of the disease in each patient, she says.
She had two patients in the trials who she believes showed improvement. “Based on my projection of their trajectory of their illness, it appeared that they progressed much more slowly,” she says.
With limited Alzheimer’s treatments on the market, Devi says Biogen’s drug may be beneficial to patients with early-onset symptoms of the disease. She points to one of her patients who has early-onset Alzheimer’s at 30 years old.
“There's very little else I can offer in terms of currently available treatments,” she says. “And it may not work with her, but it may very well be the best thing we have available to offer someone like that.”
On projecting a potential false hope onto patients
Karlawish: “... In some sense, hope is really subjective, a very personal thing. And who am I to say what's the right amount of hope? I think as a physician, as a researcher, as a writer, you know, my responsibility is to say what [do] the data say and how to make sense of them. The two studies didn't give us the answers we needed. Another study was needed. And indeed, the FDA agrees with me on that because their approval requires Biogen to conduct a, quote, new, randomized and controlled trial to verify the drug's clinical benefits. That's in the FDA's announcement.”
Devi: “I think that there are probably going to be a whole bunch of patients who are not going to be helped by this medication. And it's hard to tell which group is going to be helped. Having said that, I do know that if I were somebody with Alzheimer's disease who has the presence of plaques and tangles in the brain, I would probably think about trying it to see if it's going to help. Understanding, of course, that there is the big problem of side effects, like the brain swelling and the brain hemorrhages that have been seen with this medication.”
On one Alzheimer’s patient in the trials telling STAT News that his symptoms improved while taking Aduhelm
Karlawish: “The experience of patients in these trials is very informative. But the key thing about a drug that is being tested to see whether it slows the progression of Alzheimer's is these studies need to go on for 18 to 24 months, sometimes in duration, in order to get a good sense of how many patients [are] doing on the measures of memory, day-to-day function [and] well-being. And so I'm not discounting the patient experience. I'm saying for the purposes of deciding whether I should recommend a drug to a patient, I need the kind of data that come from a randomized and controlled trial that goes on for at least 12 to 18 months.”
On the cost of the drug — a whopping $56,000 per patient per year
Karlawish: “... If the results are inconclusive, you know, short of a cost that's pennies a day, any cost, $56,000 for example, per patient per year becomes a rather large bill. And, you know, there's a lot of other things we could do with $56,000 a year for [people] living with dementia and their family members.”
On the potential to overwhelm the health care system if people who discover they carry a genetic propensity to develop early-onset Alzheimer’s take the drug
Devi: “That is a big concern. You want to make sure that this drug is going to be used in the population of patients where it's most likely to have benefit. I think physicians, including myself, are going to be very cautious about the patients that we choose to get this medication because it's really important to understand that this drug is not without serious side effects.”
On reaction from patients
Karlawish: “We're hearing mixed stories from our patients and their family members. I think give them credit that, yes, they're desperate. I'm desperate. But I think when they hear what the controversies [are], I think certainly there are some who say, you know, ‘I'll take the risk,’ but others say, you know, ‘I don't think I'm going to pursue taking this drug.’ ”
On concerns about the drug’s controversy
Devi: “Certainly, I think this is going to be a drug whose controversy is going to continue over time. I do hope that over time, more and more people who could benefit from earlier detection of Alzheimer's disease will come to get evaluated so that if they are eligible for any of the drugs in this class, which I'm hoping there will be many more drugs in the pipeline. One of the reasons why I see patients later in the course of their condition is because the general feeling is what's the point in getting tested? What's the point in figuring out whether or not I have Alzheimer's because there's nothing to do about it anyway.
“This is the first of many big ‘mays,’ where there may be some benefit from this medication in terms of changing progression of the illness.”
This segment aired on June 10, 2021.