Despite pleas from thousands of patients and their families, Medicare officials on Thursday said they would sharply restrict access to a controversial Alzheimer’s drug developed by Cambridge-based Biogen.
The drug, the first Alzheimer’s treatment approved in nearly 20 years, will be available to only a small subset of the 1.5 million patients in the earlier stages of Alzheimer’s whom Biogen hoped would benefit from the drug. For Medicare to cover it, patients will have to be enrolled in a clinical trial, have mild rather than advanced symptoms of Alzheimer’s, and show evidence of a build-up of proteins in the brain known as amyloid plaques, a hallmark of the disease.
“We know there is potential for promise with this treatment,” said Dr. Lee Fleisher, chief medical officer of the Centers for Medicare & Medicaid Services. “However, there’s not currently enough evidence of clinical benefit to say that it is reasonable and necessary for people with Medicare.”
In a statement Thursday, Biogen said, “This unprecedented CMS decision effectively denies all Medicare beneficiaries access to Aduhelm. . . . Biogen is carefully considering its options and will provide updates as the company further evaluates the business impact of this decision.”
Although Aduhelm was approved by the Food and Drug Administration last summer, many neurologists are skeptical that the drug really works and say the risks of brain swelling and bleeding that sometimes accompany the treatment are hard to justify in the face of uncertain benefit.
CMS rarely restricts coverage of prescription drugs, and its decision to only pay for Aduhelm in the context of additional clinical trials, where its risk-benefit profile can be further studied, drew polarizing reactions from the medical community. Some doctors think the decision is a much needed correction for the FDA’s misplaced exuberance for Aduhelm.
“I absolutely agree with the agency’s decision to restrict Aduhelm,” said Dr. Aaron Kesselheim, professor of medicine at Harvard Medical School who resigned from an FDA advisory committee in protest of the agency’s decision to approve the drug.
“There is no convincing evidence yet that the drug works,” Kesselheim said, adding that it was “quite generous” of CMS to even cover treatment in clinical trials, which is normally the purview of drug companies. “I think it is a good decision given the bad decision that the FDA made in approving the drug.”
But other doctors are disturbed by the CMS decision. They say the agency is overstepping its bounds and discriminating against people with Alzheimer’s disease.
“I am disappointed,” said Dr. Stephen Salloway, director of neurology and the memory and aging program at Butler Hospital in Providence who has administered Aduhelm to patients in his clinic and has been a paid consultant to Biogen. Denying broader Medicare coverage of the drug will worsen inequities, since only wealthy people will be able to afford its $28,000 price tag, he added.
“We are treating Alzheimer’s differently than other diseases,” Salloway said. When the FDA grants an accelerated approval to drugs for cancer or other diseases, CMS nearly always covers it. “There is one standard for cancer and heart disease and there is another standard for Alzheimer’s. It is unacceptable.”
Aduhelm is designed to remove clumps of sticky proteins called amyloid plaques from the brains of people with mild cognitive impairment. Although amyloid is linked to Alzheimer’s, there is still fierce debate about whether removing it from the brain will help slow or prevent memory loss.
One clinical trial of the drug found that it caused a modest slowing of cognitive decline compared to a placebo. A second, essentially identical, trial found that the drug showed no clinical benefit. While an FDA advisory committee of neurologists voted against recommending approval of the drug, the agency itself, to the surprise of many, granted Aduhelm an accelerated approval based on its ability to lower amyloid plaques.
Multiple members of the committee, including Kesselheim, resigned in protest after FDA approved the drug. With the CMS decision Thursday, some former members expressed support for the restrictive coverage of Aduhelm.
“I find the decision to be excellent,” said Dr. David Knopman, a neurologist at the Mayo Clinic in Rochester, Minn., and a former member of the FDA advisory committee.
But Dr. Richard Dupee, chief of geriatrics service at Tufts Medical Center, said that when the FDA advisory committee voted against the drug last summer, he was initially convinced that the drug didn’t work.
But talking to Alzhiemer’s patients and their families has changed his thinking on the availability of the drug. “The vast majority of my patients and families will say, ‘Look, if it can do anything, we want it,’ ” he said.
Dupee still thinks the benefit is minimal, and Tufts has decided not to offer the drug. But he is willing to steer patients to other places that do offer it. “You are never going to reverse memory loss but you can slow it down,” he said.
Many Alzheimer’s advocates were fiercely critical of the decision. “Every day that these drugs are not available for reimbursement, a thousand patients will progress to where the drug is not effective for them anymore,” said John Dwyer, president of the Global Alzheimer’s Platform Foundation. “The drug got FDA approval. Leave it up to the doctor and the patient at this point.”
George Vradenburg, chairman of the advocacy organization USAgainstAlzheimers, said the decision sets a dangerous precedent for CMS to deny coverage of other drugs granted accelerated approvals, a process commonly used for cancer treatments.
“They have basically nullified and gutted the accelerated approval process,” he said. “This should scare the cancer community and other communities with a fatal disease on the line.”
Dr. Brian Silver, interim chair of the department of neurology at UMass Memorial Health, said CMS took a “fair” and “centered approach” by limiting coverage of the drug to clinical trials.
“They are saying, show us convincing data and we will move forward with this,” he said.
The risks of brain swelling and bleeding that occur in some people receiving the drug make it hard to justify widely prescribing something of uncertain clinical benefit, Silver added. “If this was a risk-free drug, then I think there might be less concern.”
The cost of Aduhelm looms large in any debate of its potential coverage. At launch, the drug cost $56,000 a year, and although Biogen has since cut its price in half, many experts still believe that is still too high given its unclear benefits. With more than 6 million people with Alzhiemer’s disease in the United States, covering even a small fraction of eligible patients quickly adds up to a multibillion dollar tab.
Dan Ollendorf, a health economist at the Center for the Evaluation of Value and Risk in Health at Tufts Medical Center, doesn’t think the bill is the main reason CMS proposed to restrict coverage, since Alzheimer’s care already amounts to a huge national medical expense. He thinks that if there was an unquestionably effective drug for Alzheimer’s, Medicare wouldn’t try to restrict its use, in part because an effective drug would reduce other costs to the system.
In a preliminary decision in January, CMS said its decision would apply to other anti-amyloid drugs as well, a move that was widely criticized by supporters and detractors of Aduhelm alike.
“It is stifling innovation,” Salloway said.
The agency’s final decision was slightly less restrictive. If other Alzheimer’s drugs have a proven clinical benefit, and not just evidence of lowered amyloid, CMS would cover them for all Medicare patients, Fleisher said..
Three anti-amyloid drugs, made by Eisai and Biogen, Roche, and Eli Lilly, are all undergoing clinical testing, with results expected this year or next. Fleisher, the CMS chief medical officer, said “should these drugs be approved, we can act very quickly.”