Under fire for approving a questionable drug for all Alzheimer’s patients, the Food and Drug Administration on Thursday severely curtailed 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 only been available for a few weeks, is likely to reduce the approximate number of Americans eligible for treatment from six million to 1.5 million.
Aduhelm’s approval earlier last month was one of the most controversial F.D.A. Decisions in years. Groups representing Alzheimer’s patients had campaigned heavily with the agency to sign the first new drug to treat the disease in 18 years – and the first ever developed to attack its biological foundations.
But many scientists, as well as the independent advisory committee of the F.D.A. said there was no convincing evidence that the drug worked.
In addition, the agency’s recommendation to make Aduhelm available to all Alzheimer’s patients, not just those showing early symptoms, has raised even more concern among medical professionals, including those who supported the drug’s approval.
After approval, three members of the advisory board resigned in protest. One, Dr. Aaron Kesselheim described it as “the worst regulatory decision” he could remember.
The drug’s maker, Biogen, said last month it would charge $ 56,000 annually for the drug. The associated costs – such as 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.
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Analysts expected widespread use of the drug would put a strain on Medicare’s budget. By one estimate, taxpayers could face $ 29 billion in new spending, more than the National Aeronautics and Space Administration’s annual budget.
The new guidelines do not prevent doctors from prescribing Aduhelm to patients with moderate or severe Alzheimer’s disease. But the U-turn sends a strong message to doctors and insurers as to who should get the drug.
It also greatly increases the likelihood that Medicare and private insurers will limit coverage for the drug given as a monthly intravenous infusion. That would mean that patients with moderate or severe Alzheimer’s disease would have to pay the five-digit annual costs out of their own pocket, which experts believe is unlikely.
Michael Felberbaum, a spokesman for the F.D.A., said the agency changed its recommendation following “confusion over the population intended for treatment.”
Dr. Al Sandrock, director of research and development at Biogen, said in a statement that the company “has a duty to continue listening to the needs of the community” regarding Aduhelm. Biogen’s stock is up 29 percent since the drug was approved on June 7.
When Biogen conducted clinical trials with Aduhelm, they only included people with early symptoms of cognitive decline. The drug appeared to be slightly effective at best.
In one late-stage study, the highest dose of the drug appeared to slow patients’ cognitive decline by a fraction of a point on an 18-point scale that rates their memory, problem-solving skills, and function. But in an identically designed second clinical study, the drug showed no benefit at all.
The F.D.A. approved the drug under a framework known as accelerated approval. This means that drugs that have not yet been shown to be able to help patients can be approved if they have a significant influence on a biomarker of a disease.
The agency admitted last month that there was no 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 that clumps up in plaques in the brains of Alzheimer’s patients.
However, many Alzheimer’s experts have said that there isn’t solid evidence that lowering amyloid levels has an impact on people’s cognitive problems.
At a forum sponsored last month by the Alzheimer’s Association, which pushed for Aduhelm’s approval, a panel of clinicians with differing views agreed on whether the drug should have been approved. The consensus was that Aduhelm should only be used for patients with mild stages of the disease, whose brains have high amyloid levels, and who have no medical conditions that could make them susceptible to the potentially dangerous side effects of Aduhelm.
On Thursday, Dr. Lon Schneider, director of the California Alzheimer’s Disease Center at the University of Southern California, the F.D.A. should further narrow its guidelines – which are listed on the drug’s label – for those eligible for the drug.
Dr. Schneider, who worked on one of Aduhelm’s clinical trials and turned it down, said the trials excluded people with diabetes and high blood pressure, as well as those taking blood thinners. As a result, “we don’t know of any increased risk” for these patients, he said, adding that the drug’s label should contain warnings about treating these patients with Aduhelm.
The F.D.A. is led by a transitional commissioner, Dr. Janet Woodcock, presided over because President Biden has not nominated a permanent leader. Before Dr. Woodcock became interim representative in January, and for many years was the head of the drug approval branch of the agency. Officials said she was not involved in Aduhelm’s decision despite defending it as “very solid”.
Some experts said the rapid reversal of the F.D.A. is a sign that she mishandled her initial review and is now closer to where she should have started.
“The revision of this label is another piece of evidence that should worry the American public, as F.D.A. practices his regulatory science, ”said Dr. Jason Karlawish, co-director of the University of Pennsylvania Penn Memory Center.
The consequences of initial approval of the drug are still spreading.
In Congress last month, two House committees announced an investigation into Aduhelm’s approval and price. Senators from both parties have also called for an investigation in this chamber.
The researchers said that such outside control was important because the drug controversy and the F.D.A. “This event only adds to the importance of these Congressional hearings to find out what is going on at F.D.A. and why they do that, ”said Dr. Karlalish.
Some analysts said tightening approval for the drug could help Biogen deflect criticism from lawmakers. “This helps your case say, ‘Hey, we’re not just pushing the envelope as hard as we can,'” said Brian Skorney, analyst at Robert W. Baird & Company. He said he expects Aduhelm to generate $ 7.5 billion in sales 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 few months due to the challenges of administering it.
The limited guidelines of the F.D.A. apply only to people who start taking the drug. Mr Felberbaum, the spokesman, said that some patients on Aduhelm whose symptoms become more severe “could benefit from ongoing treatment”.
The caveat is that there is no scientific evidence that Aduhelm will help such people.