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 early 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 diagnosis 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 because of 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 significantly 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, an FDA spokesman, said the agency changed its recommendation after “confusion over the intended population for treatment.”
Dr. Al Sandrock, head 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 shown that they can help patients can be approved if they have a significant influence on a biomarker of a disease.
In the case of Aduhelm, the FDA admitted last month that there was no convincing evidence that the drug was slowing patients’ cognitive decline. Instead, the agency approved Aduhelm for its 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 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 was pushing for Aduhelm’s approval, a panel of clinicians with differing views agreed on whether the drug should have been approved, that its use should be restricted. 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 do not have certain 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 excluded people with diabetes and high blood pressure, as well as blood thinners. As a result, he said, “we do not know of any increased risk” for these patients and the label on the drug should contain warnings against treating these patients with Aduhelm.
The FDA is currently headed by a transitional commissioner, Dr. Janet Woodcock, as President Biden has not appointed a permanent director of the agency. 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 fact that the FDA reversed course so quickly is a sign that the agency 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 aftermath of the drug’s initial approval by the FDA is 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.
Scientists said such outside scrutiny is important as drug controversy and FDA decision-making swirl. “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.
Biogen has not yet announced how many patients have received the drug to date, but its distribution is expected to be slow in the first few months due to administration challenges.
The FDA’s restricted guideline only applies when people start taking the drug. FDA spokesman Mr. Felberbaum said that some patients who take Aduhelm and 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.