In Reversal, F.D.A. Requires Limits on Who Will get Alzheimer’s Drug

In Reversal, F.D.A. Calls for Limits on Who Gets Alzheimer’s Drug

Under fire for approving a questionable drug for all Alzheimer’s patients, the Food and Drug Administration on Thursday severely curtailed its previous recommendation, 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 FDA 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 FDA’s independent advisory committee, said there was no convincing evidence that the drug worked.

Additionally, the agency’s recommendation to make Aduhelm available to all Alzheimer’s patients, not just those showing early symptoms, has created 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.

    • New drug approved: The FDA approved the first new Alzheimer’s treatment in 18 years and the first to attack the disease process.
    • Is a new drug working?: Patient populations are desperate for new options, while several prominent Alzheimer’s experts and the FDA’s independent advisory committee have objected to the approval over concerns about the lack of adequate evidence of efficacy.
    • Understanding Alzheimer’s Disease: Get answers to frequently asked questions about the disease that affects approximately 30 million people worldwide.
    • A 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 onset of symptoms and look to the future.

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 FDA, said the agency changed its recommendation after “confusion over the intended population 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 FDA has 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 was slowing patients’ cognitive decline. Instead, it based its approval on the drug’s ability to reduce levels of a protein called amyloid, which forms plaques in the brains of Alzheimer’s patients.

However, many Alzheimer’s experts have said that there is no solid evidence that lowering amyloid levels affects people’s cognitive problems.

At a forum sponsored last month by the Alzheimer’s Association, which was pushing for Aduhelm’s approval, a panel of clinicians with differing views agreed on whether the drug should have been approved and said its use was restricted should be. 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 FDA should further restrict its guidelines – which are listed on the drug’s label – for those people eligible for the drug.

Dr. Schneider, who worked on one of Aduhelm’s clinical trials and spoke out against approval, said the trials had excluded people with diabetes and high blood pressure, as well as people 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 FDA 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 FDA’s speedy reversal was a sign that it mishandled its initial review and is now closer to where it should have started.

“The revision of this label is another piece of evidence that should concern the American public with how the FDA practices its 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 such outside control was important because the controversy swirled around the drug and the FDA’s decision-making. “This event only adds to the importance of these Congressional hearings to find out what is going on at the FDA and why they are doing it,” said Dr. Karlawish.

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 boundaries as hard as we can,'” said Brian Skorney, analyst at Robert W. Baird & Company. He said he expected 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 FDA’s restricted guideline only applies when people 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.


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