Under fire for approving a questionable drug for all Alzheimer’s patients, the Food and Drug Administration on Thursday greatly narrowed its previous recommendation and is now suggesting that only those with mild memory or thinking problems should receive it.
The reversal, highly unusual for a drug that has been available for only a few weeks, is likely to reduce the approximate number of Americans who are eligible for the treatment to 1.5 million from six million.
The approval of Aduhelm early last month was one of the most contentious F.D.A. decisions in years. Groups that represent Alzheimer’s patients had intensely lobbied the agency to sign off on the first new drug to treat the disease in 18 years — and the first ever designed to attack its biological underpinnings.
But many scientists, as well as the F.D.A.’s independent advisory committee, said there was not convincing evidence that the drug worked.
In addition, the agency’s recommendation that Aduhelm be available to all Alzheimer’s patients, not just those showing early symptoms, stirred up even more concern among medical experts, including those who had supported the drug’s approval.
After the approval, three members of the advisory committee resigned in protest. One, Dr. Aaron Kesselheim, described it as “the worst approval decision” that he could remember.
The drug’s maker, Biogen, said last month that it would charge $56,000 annually for the drug. Associated costs — such as for diagnostics and safety monitoring, since the drug’s side effects include brain swelling and bleeding — could add tens of thousands of dollars to each patient’s annual bill.
- New Drug Approved: The F.D.A. approved the first new Alzheimer’s treatment in 18 years, and the first to attack the disease process.
- Does New Drug Work?: Patient groups are desperate for new options, while several prominent Alzheimer’s experts and the F.D.A.’s own independent advisory committee objected to its approval, having raised concerns over lack of sufficient evidence of its effectiveness.
- Understand Alzheimer’s Disease: Get answers to common questions about the disease, which affects about 30 million people globally.
- One Face of Alzheimer’s: This profile of a woman in the early stages of the disease shows what it can be like to face the beginning symptoms and to consider the future.
Analysts expected that the drug’s widespread use would strain Medicare’s budget. By one estimate, it could leave taxpayers on the hook for $29 billion in new spending, more than the annual budget of the National Aeronautics and Space Administration.
The new guidance does not prevent doctors from prescribing Aduhelm to patients with moderate or severe Alzheimer’s. But the about-face sends a strong message to doctors and insurers about who should receive the drug.
It also substantially increases the odds that Medicare and private insurers will restrict coverage of the drug, which is given as a monthly intravenous infusion. That would mean that patients with moderate or severe Alzheimer’s would have to pay the five-figure annual costs out of their own pockets, which experts regard as unlikely to happen frequently.
Michael Felberbaum, a spokesman for the F.D.A., said the agency had changed its recommendation after “confusion regarding the intended population for treatment.”
Dr. Al Sandrock, Biogen’s head of research and development, said in a statement that the company was “committed to continue to listen to the community’s needs” regarding Aduhelm. Biogen’s stock has soared 29 percent since the drug was approved on June 7.
When Biogen conducted clinical trials of Aduhelm, it included only people with early symptoms of cognitive decline. The drug appeared slightly effective, at best.
In one late-stage trial, the highest dose of the drug appeared to slow patients’ cognitive decline by a fraction of a point on an 18-point scale that assesses their memory, problem-solving skills and function. But in an identically designed second clinical trial, the drug showed no benefit at all.
The F.D.A. signed off on the drug under a framework known as accelerated approval. That allows drugs that have not yet shown they can help patients to be approved if they have a substantial effect on a biomarker of a disease.
The agency acknowledged last month that there was not convincing evidence that Aduhelm slowed patients’ cognitive decline. Instead, it based its approval on the drug’s ability to reduce levels of a protein called amyloid, which clumps into plaques in the brains of Alzheimer’s patients.
But many Alzheimer’s experts have said there is not solid evidence that reducing amyloid levels has any effect on people’s cognitive problems.
At a forum last month sponsored by the Alzheimer’s Association, which had pushed for approval of Aduhelm, a panel of clinicians with varying views of whether the drug should have been approved were united in saying its use should be limited. The consensus was that Aduhelm should be only for patients in mild stages of the disease whose brains have high levels of amyloid and who don’t have medical conditions that could make them vulnerable to Aduhelm’s potentially dangerous side effects.
On Thursday, Dr. Lon Schneider, director of the California Alzheimer’s Disease Center at the University of Southern California, said the F.D.A. should further narrow its guidelines — which are listed on the drug’s label — for who is eligible for the drug.
Dr. Schneider, who worked on one of the clinical trials of Aduhelm and opposed its approval, said the trials had excluded people with diabetes and high blood pressure and those taking blood thinners. As a result, “we don’t know any extent of increased risk” for those patients, he said, adding that the drug’s label should include warnings about treating those patients with Aduhelm.
The F.D.A. is being run by an interim commissioner, Dr. Janet Woodcock, because President Biden has not nominated a permanent leader. Before becoming interim commissioner in January, Dr. Woodcock was the longtime leader of the arm of the agency responsible for approving drugs. Officials said she was not involved in the Aduhelm decision, though she has defended it as “very solid.”
Some experts said the F.D.A.’s quick reversal was a sign that it had mishandled its initial review and was now ending up closer to where it should have started.
“The revision of this label is yet another piece of evidence that should cause the American public to be concerned about how F.D.A. is practicing its regulatory science,” said Dr. Jason Karlawish, a co-director of the University of Pennsylvania’s Penn Memory Center.
The fallout from the initial approval of the drug is still spreading.
In Congress, two House committees last month announced an investigation into Aduhelm’s approval and price. Senators from both parties have called for an investigation in that chamber, too.
Researchers said such outside scrutiny was important because of the controversy swirling around the drug and the F.D.A.’s decision-making. “This event only adds to the importance of having those congressional hearings to figure out what’s going on at F.D.A. and why they’re doing this,” Dr. Karlawish said.
Some analysts said the narrower eligibility for the drug could help Biogen deflect criticism from lawmakers. “This helps their case to say, ‘Hey, we’re not just completely pushing boundaries as hard as we can,’” said Brian Skorney, an analyst at Robert W. Baird & Company. He said he expected Aduhelm to generate $7.5 billion in revenue for Biogen in 2025.
Biogen has not yet announced how many patients have received the drug, but its distribution is expected to be slow in the first months because of challenges administering it.
The F.D.A.’s narrowed guidance only applies to when people start taking the drug. Mr. Felberbaum, the spokesman, said some patients on Aduhelm whose symptoms grow more severe “may benefit from ongoing treatment.”
The caveat is that there is no scientific evidence that Aduhelm will help such people.