Federal officials are wrestling with a decision that could go a long way toward determining the future of the controversial new Alzheimer’s drug, Aduhelm, and whether significant numbers of patients use it.
In January, Medicare, the federal health insurance program for people 65 and over, plans to issue a preliminary decision on whether it will cover the expensive medication. The Food and Drug Administration’s approval of Aduhelm in June has drawn fierce criticism because clinical trials showed the drug had significant safety risks and unclear benefit to patients.
Roughly 80 percent of potential Aduhelm patients are old enough to receive Medicare, making the program’s coverage decision crucial. Private insurers often follow Medicare’s lead.
Medicare almost always pays for F.D.A.-approved drugs, at least for the medical conditions designated on their label, health policy experts said. But with Aduhelm, Medicare officials have undertaken a monthslong review that could result in no coverage, full coverage or limited coverage.
“It’s truly unprecedented,” said James Chambers, a researcher at the Center for the Evaluation of Value and Risk in Health at Tufts Medical Center.
Chiquita Brooks-LaSure, the administrator of the Centers for Medicare and Medicaid Services, or C.M.S., declined to discuss the deliberations. “It’s a process our coverage team goes through,” she said. “We will let the scientists continue their work.”
Aduhelm, made by Biogen, is a monoclonal antibody also known by its scientific name, aducanumab. Patients receive it in monthly infusions and also require regular M.R.I. scans to monitor for potentially dangerous side effects, including brain swelling and bleeding.
Last week, following weak sales, Biogen slashed Aduhelm’s price, to $28,200 a year from $56,000.
In a statement, Michel Vounatsos, Biogen’s chief executive, said: “It is a critical time for the Alzheimer’s disease community as the Centers for Medicare and Medicaid Services (C.M.S.) is considering the possibility of coverage of not only Aduhelm, but also this entire new class of Alzheimer’s disease therapies. We hope our actions today will facilitate patient access to these innovative Alzheimer’s treatments.”
The new price is still much higher than many analysts have said is warranted.
The total cost to Medicare would depend on the terms it sets and how many patients decide to use Aduhelm. About 1.5 million Americans may be eligible because they have mild Alzheimer’s-related dementia.
“While it of course depends on Aduhelm’s utilization, it seems that even at $28,000 a year, Aduhelm would still be one of Medicare’s biggest drug expenses,” Dr. Chambers said.
Before Biogen’s price cut, Medicare’s actuarial division, acting without knowing what the coverage decision would be, imposed one of the biggest-ever increases in Medicare Part B premiums for 2022, partly driven by the possibility of Aduhelm coverage.
Medicare’s review comes as Aduhelm faces criticism and hurdles around the world.
Reviewers at the European Union’s drug regulator, the European Medicines Agency, recommended against approving the drug, a decision that Biogen is requesting be re-examined. Leading Canadian Alzheimer’s research organizations earlier said that approving Aduhelm in Canada “cannot be justified.”
Large American medical systems, including Cleveland Clinic, Mount Sinai Health System, Mass General Brigham and the Department of Veterans Affairs have declined to offer Aduhelm.
The American Academy of Neurology said recently that if Aduhelm was covered by Medicare, which typically pays 80 percent of a drug’s price, “many beneficiaries would pay thousands of dollars of out-of-pocket costs for a drug with substantial risks and without proven clinical benefit.”
During the evaluation process, Medicare officials have met with stakeholders, including supporters of coverage, like Biogen and the Alzheimer’s Association, a leading patient group.
“We have been engaging with C.M.S. towards the goal of providing access in a way that is sustainable for Medicare beneficiaries and the health care system,” Biogen said in a statement.
Medicare officials have also met with those that oppose coverage or want it sharply narrowed, like the American Geriatrics Society and the Blue Cross Blue Shield Association, which, during a public comment period this summer, wrote: “We feel strongly that aducanumab does not meet the statutory coverage standard of ‘reasonable and necessary’ as the current evidence highlights numerous safety risks and uncertain clinical benefits.”
In approving Aduhelm, the F.D.A. acknowledged that there was insufficient evidence it would help patients, but greenlighted it under a program called “accelerated approval,” which allows authorization of unproven drugs for serious diseases with few treatment options if the drug affects a biological mechanism in a way considered “reasonably likely to predict clinical benefit.”
As its justification, the agency cited Aduhelm’s reduction of a protein, amyloid, that forms plaques in the brains of people with Alzheimer’s. But many Alzheimer’s specialists say that extensive research has shown little evidence that reducing amyloid slows cognitive decline.
In evaluating Aduhelm, Medicare officials are supposed to decide if it is a “reasonable and necessary” treatment, a phrase that usually “means adequate evidence of improved health outcomes,” said Dr. Sean Tunis, a former official with C.M.S. who is now a senior fellow at the Tufts center.
“If you go strictly by what the language is, this doesn’t meet Medicare’s ‘reasonable and necessary’ criteria because the F.D.A. themselves says there’s no direct evidence of improved cognition,” said Dr. Tunis, who also works as a consultant, including advising Biogen, before Aduhelm was approved, about Medicare’s various options for coverage. He added that the F.D.A.’s requirement that Biogen conduct another trial (which will take years while Aduhelm is available to patients) “implies that the cognitive benefits have not yet been shown.”
If Medicare coverage for Aduhelm is denied, Dr. Tunis said, “to my knowledge, it will be the first time ever that C.M.S. has declined to pay for a drug that was approved by the F.D.A. for its on-label indication.”
Dr. Chambers said Medicare had occasionally denied coverage for medical devices approved by the F.D.A., which can have lower evidentiary standards for devices than for medicines. But he said Medicare might be reluctant to do so for a drug. And since both C.M.S. and the F.D.A. are part of the Department of Health and Human Services, “it will definitely be a lot to explain for the people at C.M.S. to say, ‘Yeah, we just don’t happen to agree with our sister agency,’” Dr. Tunis said. “That’s awkward.”
Medicare’s decision will also establish standards for evaluating several similar Alzheimer’s drugs in the pipeline.
If Medicare covers Aduhelm, the agency could limit it to specific types of patients, like those with mild Alzheimer’s-related cognitive problems, similar to participants in the clinical trials. (The F.D.A. initially approved Aduhelm for all Alzheimer’s patients, but after objections from medical experts, it narrowed the label to patients in mild stages.) Medicare could also require administration by certain specialists and impose strict safety monitoring.
Or it could place Aduhelm under a framework called Coverage With Evidence Development, which allows payment only for patients participating in clinical trials or whose data is collected in a registry. While that would allow collection of information about Aduhelm from patients, it would not prove whether the drug works because it would not compare outcomes for people not receiving Aduhelm, Dr. Chambers said.
The high-stakes coverage decision, expected to be finalized by mid-April after a public comment period, has drawn impassioned and detailed opinions, reflected in comments posted on the C.M.S. website.
“Please, please, please, do not cover this medicine,” implored Dr. James Castle, an Illinois neurologist who treats Alzheimer’s patients. “Send a strong and clear message to the pharmaceutical industry that they need to show proof of both efficacy and safety before releasing their medicines on the market.”
Posts supporting coverage include comments from people who have consulted for Biogen, like Dr. Jeffrey Cummings, a research professor in the department of brain health at the University of Nevada Las Vegas. He wrote that the drug “prolongs the mental life of our declining patients,” adding, “Medicare should unequivocally support coverage for aducanumab, and they should do it as soon as possible.”
Dr. Cummings and several others who earned fees from Biogen were among 25 signatories of another letter on the site. Supporting comments also came from officials of the Infusion Access Foundation and Eli Lilly, which has developed a similar anti-amyloid drug.
One neurologist, Dr. David Weisman, who said he was not involved with aducanumab’s trials but had worked with other anti-amyloid drugs, wrote that Medicare should require safety monitoring and medical expertise. But because the F.D.A. approved Aduhelm, he wrote, whether to use it “should be left to individual patients, family members and physicians.”
More people signed individual or group comments that opposed coverage or said it should be strictly limited.
“It was a bit surprising how much of the public comment content was actually saying cautionary things or was not in favor of coverage,” said Dr. Tunis, who has also advised an advocacy group that supports Aduhelm’s approval, UsAgainstAlzheimer’s, about how data could be collected if Medicare requires that. “It’s more common actually to have comments that advocate in favor of coverage,” he said.
Commenters cited many reasons for opposition or caution. Besides inadequate evidence of benefit, they mentioned inequities that could worsen because Medicare coverage wouldn’t include all treatment costs; unknowns about Aduhelm’s effects on nonwhite patients, since most trial participants were white; and risks that profit-seeking clinics could prey on the desperation of patients and families.
One letter, signed by 180 Alzheimer’s doctors, raised numerous issues, including “harms that people may experience on aducanumab in the real world, outside of a clinical trial setting” given that participants in the drug’s clinical trials were “younger and in earlier stages of cognitive decline, had fewer comorbidities, and were much better monitored than patients will be under conditions of broad Medicare coverage.”
An author of that letter, Dr. Michael Greicius, medical director of the Stanford Center for Memory Disorders, said, “I’m still quietly hoping that January is going to roll around and they’re going to say: ‘Look, we’re not going to cover this. The evidence is too poor.’”
Reed Abelson contributed reporting.