Why the FDA Approved a Controversial Alzheimer’s Drug

Aducanumab is the first new Alzheimer's disease treatment in nearly 20 years. So when the Food and Drug Administration (FDA) granted accelerated approval to the drug June 7, many patients and advocates were elated despite its $56,000 annual cost. But the announcement has done little to quiet the debate within the medical community about the drug's questionable effectiveness and the agency's procedures in granting it accelerated approval.

Credit: REUTERS/Brian Snyder via PBS NewsHourr

Developed by Biogen, aducanumab is a monoclonal antibody that targets and clears amyloid proteins in the brain. These toxic proteins are thought to be a marker of Alzheimer's disease.

The FDA's drug approval was based on two clinical trials. One showed some improvement in patients who'd been given aducanumab, but the other found no benefit.

A number of practitioners said that was not good enough and that the drug fell short of FDA's usual standards for approval. And, in November 2020, an outside advisory board recommended that FDA not approve the drug.

But other medical professionals said the need was so great that any medication offering promise was worth trying. The last treatment for Alzheimer's came on the market some 18 years ago.

Next Avenue has been following the developments in Alzheimer's treatments for years due to their importance to our readers. We are committed to helping you understand this latest news by providing insight and in-depth information about the decision.

What follows is a PBS NewsHour interview with Pam Belluck, a health reporter for The New York Times who has been covering this issue. She discussed the FDA's announcement with PBS NewsHour's Amna Nawaz.

Amna Nawaz: Even with this disagreement over how effective drug is, the FDA still approved it. Why? What do we know about what they based that [decision] on?

Pam Belluck: They actually acknowledged that there was not clear evidence of clinical benefit [for trial participants who took the drug], that there was some kind of murkiness in the evidence about whether this [treatment] will actually help patients slow down their memory and thinking problems.

But what they said is, 'There is some suggestion of that [outcome].' And one thing that everybody on all sides agree that the drug does do is that it attacks a key protein in Alzheimer's disease. This is a protein called amyloid. And it is the protein that clumps into plaque in the brains of people who have Alzheimer's.

So, they said, 'Well, we are going to approve this drug because it can attack the biology of the disease. We have some signal that there might be some benefit for patient symptoms, and we are going to tell the company that they need to do another clinical trial (the FDA is requiring Biogen to conduct a new clinical trial).'

If the results of that trial do not show a benefit, then the FDA might revoke the approval, and it could end up being that those trials don't show a benefit at all.

The issue with that [approach] is that the clinical trial takes three or four [to] five years. And so this drug will be on the market, patients will be using it without actually being certain that it has the ability to help them.

I am assuming there will be high demand for [the drug] with millions of people in the U.S. suffering from Alzheimer's. Do we know enough about the benefits and the risks at this point? What did they find in the trials in terms of the risks that people take on in taking this drug?

Yes, there is definitely a risk.

This drug can cause brain swelling and brain bleeding. About forty percent of patients in the [clinical] trial did experience that. Now, it is not quite as serious as it sounds, because most of those cases didn't actually produce any symptoms for patients. But some number did.

And about six percent of patients had to quit the trials [due to] brain swelling or brain bleeding. So those can be serious side effects. As a result, anybody who takes this drug will have to have regular brain MRIs to check to see if their brain is experiencing anything like this.

In terms of the benefit that they found — as you said, in the beginning, only one trial found any benefit. Another completely identical trial did not find any benefit. The benefit in the trial that did seem to be positive is actually quite slight.

So, some of the scientists who were concerned and arguing against approval were saying, 'We don't have a slam-dunk here. We only have one trial that shows any possibility of benefit. And that benefit itself is pretty slight.' And then, on the other side, we know that there is a risk. And so they were saying the potential benefit here doesn't outweigh the risk.

When the FDA issues approval, that implies this drug is safe, this is OK to use, and this is effective. There doesn't seem to be a clear-cut case for this here. So what is the role of the FDA in all of this?

I think the FDA is looking at the seriousness of this disease, the fact that millions of people have it, that there is very little on the market that actually helps for more than a few months.

And they are saying that this drug seems to have a hint of benefit and it goes after this key protein of amyloid. And that is what they are sort of banking on. Now, there isn't a lot of really strong history with drugs that have tried to attack amyloid. There is about twenty-five years of failed clinical trials with anti-amyloid drugs.

They have succeeded in knocking down the protein, in clearing it out of the brain, but they have not succeeded in producing any benefit that people would actually notice in terms of their symptoms.

So, that is kind of the gamble that the FDA is taking here. They are saying, 'We think this [drug] is going to be the one that sort of crosses that threshold. We think that its ability to get rid of amyloid in your brain is actually going to help you see that your memory loss declines at a slower rate.'

(This article appeared previously on PBS NewsHour.)