Coverage of Alzheimer’s drug Aduhelm limited due to concerns about effectiveness, safety
One of the first things you notice when you walk into Laurie Waters' Clover, South Carolina, home is the wall of New England Patriot photos. Waters points out that the word “Patriots” is even emblazoned on her wedding band.
Today, her Patriots memories are still strong. But Waters, who has Alzheimer's disease, said she’s worried they won’t stay with her. She also worries about her quality of life — now and in the future.
Her husband started noticing changes in Waters six years ago.
“I wasn’t coming out for my coffee. I’d leave it in the Keurig. I wasn’t eating. I was messing up on things,” Waters said.
She couldn’t remember the names or faces of some work colleagues or things she’d just read. Afraid to make a mistake, she had to quit the job she loved helping terminal cancer patients get affordable medicine.
“It’s scary because I know that someday I’m going to wake up and it’s all going to be gone," she said. “I’m not going to remember my grandchildren and I’m not going to remember my husband.”
But a new Alzheimer's drug, Aduhelm, gave Waters hope. The company that makes it said it eliminates the plaque in the brains of many Alzheimer’s patients. The FDA approved it last summer.
“That medication actually for me personally could stop Alzheimer's in its track where I’m at,” Waters said. “It’s going to give me how many more years with my grandchildren? How many more years with my husband?”
“It’s going to give me how many more years with my grandchildren? How many more years with my husband?”— Laurie Waters
Waters’ high expectations for Aduhelm are common among many Alzheimer’s patients. But the drug is also the subject of intense medical and political debate. For one thing, there’s cost. The drug’s approval has contributed to a significant increase for everyone on Medicare. But the larger problem is that it may not work, said Harvard Medical School's Dr. Aaron Kesselheim.
“There is no evidence that it slows progression of the disease — yet," Kesselheim said. "There is conflicting evidence that it might do that."
'There was a big concern about the risks of the drug'
Kesselheim was a member of the FDA Advisory Committee that evaluated the data on Aduhelm. In one of two clinical trials run by Biogen, the company that makes the drug, the disease progressed a bit more slowly. In the other, the placebo group did better, Kesselheim said.
And even under the best possible interpretation of the data, Aduhelm slows the disease’s progress by only four months, according to an independent evaluation published later by the Institute for Clinical and Economic Review.
The committee voted 10-0 to deny the drug’s approval.
“We all voted that evidence of benefit didn’t seem to be very convincing, but yet there was a big concern about the risks of the drug,” Kesselheim explained.
Approximately 40% of those evaluated developed side effects like brain swelling or bleeding. And in 1% of the cases, those complications were grave.
“That swelling and bleeding, if it isn’t acted on quickly can lead to very substantial bad outcomes,” Kesselheim said.
Substantial bad outcomes include things like blindness or brain damage.
But last summer, the FDA approved Aduhelm anyway. It did so because Aduhelm reduces the amyloid plaque on the brains of many Alzheimer’s patients. It’s not at all clear from the science that eliminating that plaque slows the disease, Kesselheim said. But the FDA said plaque reduction means Aduhelm is “reasonably likely” to ultimately result in “clinical benefit” like reducing symptoms.
In order to approve a drug without proof of its clinical benefit, the FDA had to change course. It used an alternative approval process that allows it to OK drugs that affect an intermediate step — like reducing tumor size in cancer patients. Because if tumors shrink enough, patients are likely to live longer.
But, Kesselheim said, "there are a lot of questions about the amyloid hypothesis” and whether reducing plaque slows the progression of Alzheimer's disease.
And accelerated approval is typically reserved for promising drugs that haven’t been through clinical trials, Kesselheim said. It’s not supposed to be used for medicines that have already been through those trials and failed to show those benefits.
“It seemed as if they were changing their approach in order to approve the drug rather than changing their approach on the basis of the science behind the drug,” Kesselheim said.
Kesselheim called it the “worst drug approval in recent U.S. history.” He and two other advisory board members resigned in protest, and a number of prestigious medical centers, including Johns Hopkins and the Cleveland Clinic, are refusing to administer it.
And there are questions about the approval process. There have been reports of secret meetings between the manufacturer, Biogen and the FDA, in violation of FDA policy. The FDA and Biogen declined requests for interviews. The approval is now being investigated by the Federal Trade Commission, the Securities and Exchange Commission and the Inspector General for the Department of Health and Human Services and two congressional committees.
At least 6.5 million Americans have Alzheimer's
Congress also wants Biogen to explain why it initially set the price at $56,000 a year. That was enough to bankrupt Medicare, said UCLA doctor John Mafi.
“There was literally not enough money to pay for it,” Mafi said.
So the approval meant premiums had to go up. Last fall, Medicare increasedpremiums by $260 a year, saying half of the increase was because of Aduhelm.
The Alzheimer’s Association estimates that 6.5 million Americans older than 65 have the disease. And if only half a million of them took Aduhelm, Medicare would have had to spend $29 billion a year on that one drug a Kaiser Family Foundation analysis showed.
Mafi, who studies the impact of health care costs on older people, said that increase is tough on seniors.
“It would maybe start to force people to decide between having to pay for food, rent and other things,” Mafi said.
With disappointing sales, Biogen ended up cutting the price to $28,200. Medicare now says it will likely be able to reduce premiums.
But in January, Medicare announced it would review the science behind Aduhelm, evaluating its effectiveness and potential for harm. And it said it was considering limiting coverage to those taking the drug as part of a clinical trial.
Laurie Waters said that rules her out. She’d have to travel three hours away from her home to Charleston three days a week to participate. She was devastated.
“It should be up to myself, my doctors and us to determine if we should take it,” Waters said.
Waters said Medicare is discriminating against Alzheimer’s patients, particularly people who can’t easily access clinical trials, like those who live in rural areas and people of color.
She’s one of hundreds of the Alzheimer’s Association’s advocates with Congress.
“When I walk up and see a congressman or senator and they look in my eyes, they remember me when a bill comes in front of them, and they’re like, wow,” Waters said.
Medicare’s announcement prompted a massive lobbying campaign by Biogen, the drug trade association PhRma and Alzheimer’s advocacy groups. Seventy-eight House Republicans, — including five from North and South Carolina, — sent Medicare a letter expressing concern that it was unfairly restricting the drug. Then there was another letter from a bipartisan group that included three North Carolina representatives. This one worried Medicare's decision would disproportionately affect "disadvantaged communities."
But last month, Medicare announced it’s holding firm. It will only pay for the drug for people in clinical trials, although it also encouraged more diversity in those trials.
In Part 2 of this series, we'll look at the Alzheimer's Association's efforts to build support for Aduhelm and similar drugs.