Biogen, the drug company, said Tuesday that it would ask the Food and Drug Administration to approve an experimental drug, aducanumab, to treat people with mild cognitive impairment and the earliest signs of Alzheimer’s disease.
About 10 million Americans might qualify for treatment if the drug were approved, according to Michel Vounatsos, the company’s chief executive. Even so, it is not quite time for these patients to celebrate.
The company has not published the most recent analyses, and experts are mostly in the dark as to how well the drug works. It neither prevents nor cures Alzheimer’s; the company claims only that aducanumab may slow cognitive decline in some patients.
In fact, Biogen announced in March that it was halting two large studies of aducanumab for treatment of Alzheimer’s disease because data showed the effort was likely to be futile.
The company resurrected the drug after additional analyses suggested it might have some effect at higher doses. (“Just in time for Halloween, aducanumab has risen from the dead,” one drug industry analyst said in an email.)
Here are some takeaways from Tuesday’s announcement.
What is this drug?
Drug companies have spent billions of dollars on failed trials for Alzheimer’s drugs. So frustrating have the findings been that some have decided to abandon the search altogether.
Aducanumab is a monoclonal antibody, an expensive type of drug that attaches to specific proteins in order to disable them. The drug clears a key protein in Alzheimer’s disease — beta amyloid — that accumulates in plaques in patients’ brains.
Aducanumab is given as an intravenous infusion once a month. The hope was that if patients were treated early in the course of the disease, their brains might recover or the disease’s progress might be slowed.
What did the studies find?
Each study had about 1,600 patients, and brain scans in patients showed that the drug reduced the amount of beta amyloid in the brain. In one study, cognitive decline also slowed; in the other, patients experienced no clinical benefit.
But the company changed the design of the second study midway through to give one group of patients a higher dose. As of March, the change had brought no clinical benefit. But as more data came in, officials say, the picture changed.
Biogen now has data from twice as many patients, from both clinical trials, and executives used those results to justify seeking approval. But the findings have not been published in a peer-reviewed journal, and experts have plenty of questions about whether aducanumab actually works, and if so, how well.
The company plans to present its analyses at a scientific meeting in December.
If the drug was deemed a failure, why are we talking about it?
Some 5.5 million Americans have Alzheimer’s disease, not including those in the very early stages, and there is no effective treatment. The consequences for patients and caregiving families are devastating.
Biogen officials contend the additional study data showed a slower cognitive decline in the subgroup of patients who got the highest dose. That finding, plus the somewhat positive results from the other study, may be enough to convince the FDA that the drug works.
Biogen met with agency officials Monday, and they told the company that it was “reasonable to file” for approval, Vounatsos said.
An FDA spokesman said the agency does not comment on investigational drugs or on drug approval applications.
Why the hesitation?
First, Biogen has provided only a summary of its data and analyses. When Alzheimer’s specialists see the details in December — better yet, when there is a peer-reviewed published paper — they may not be convinced the drug has meaningful benefits.
Second, the new analysis of patients receiving high doses is a risky one. In a so-called subgroup analysis, it is too easy to slice the data to justify a conclusion — that’s why large randomized trials with defined end points are so valuable. Ordinarily, a subgroup analysis is considered a way to generate a hypothesis, not a way to test whether it is true.
Dr. Ronald Petersen, an Alzheimer’s researcher at the Mayo Clinic who consults for Biogen, pointed out that the company had not yet convinced the FDA of the drug’s efficacy.
“They are just allowed to file — no guarantees on approval,” he said. “But it gives the drug a chance.”
What if aducanumab actually works?
If it succeeds, the drug would be a triumph, “the dawn of a new era,” said Dr. Michael Weiner, an Alzheimer’s researcher at the University of California, San Francisco.
Still, “this is not a cure,” he added. “It is a slowing of decline. The practical impact on patients remains to be seen.”
An approval would mean a windfall for Biogen. If aducanumab were approved, it could bring in $10 billion or more in annual sales, according to Guggenheim Securities.
But with so little data released by the company, researchers are cautious. “Looks very encouraging, but I would need to see more details,” said Dr. Murali Doraiswamy, an Alzheimer’s expert at Duke University.