Medicare officials on Tuesday proposed covering a pricey, controversial Alzheimer’s drug but, in a highly unusual step, restricted it to people enrolled in approved clinical trials, sharply limiting the number of eligible patients.
The move was seen as a severe disappointment by some patients and advocates who believe the drug, made by Massachusetts-based Biogen, is the first treatment that can change the course of the devastating disease, slowing cognitive decline in early-stage patients. Other Alzheimer’s drugs treat symptoms rather than targeting the underlying pathology.
But the action was praised by critics, some of whom said the drug never should have been approved by the FDA, and others who are uncertain about its effectiveness. They argued the new trials will help determine whether the drug works, a matter of heated debate since the FDA approved Aduhelm in June for people with early-stage Alzheimer’s or mild cognitive impairment due to the disease.
The drug had been viewed as a potential blockbuster and budget buster. Biogen originally priced Aduhelm at $56,000 a year per patient, later cutting that to $28,200.
Some physicians called the CMS decision a good compromise.
“It’s a middle road that is good for the field, good for the patients and good to determine the efficacy of this class of treatments,” said Ronald C. Petersen, director of the Mayo Clinic Alzheimer’s Disease Research Center. “It’s not a perfect solution. But it is better than covering it carte blanche or not covering it at all.”
CMS officials, in a call with reporters explaining the tentative ruling, acknowledged the decision was unusual, but said it was appropriate.
“It’s important to recognize the FDA approved the drug under an accelerated approval program,” said Lee A. Fleisher, director of CMS’s center for clinical standards and quality. While the FDA found the drug safe, it based its conclusion about whether the drug worked not on its effect on patients but on its ability to reduce amyloid — something the FDA said had a reasonable likelihood of benefiting patients.
Fleisher noted that while the treatment might be promising, it also has the potential of seriously harming patients. Side effects include headaches, dizziness, falls and brain bleeds. He added that CMS believes “any appropriate assessment of patient outcomes must weigh both harm and benefits before arriving at a final decision.”
If the proposed decision is finalized, CMS would issue criteria for clinical trials, which would be randomized controlled trials, with some patients getting placebos. In qualifying trials, Medicare participants would be eligible to receive coverage of the drug, related services and other routine costs, which may include brain scans to check for amyloid in the brain.
“Before finalizing this proposal, we will have more opportunities to hear from people with Medicare living with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease dementia, their family members and caregivers, as well as many other stakeholders, including patient advocacy groups, medical experts, states, payers, and industry professionals,” Chiquita Brooks-LaSure, the CMS administrator, said in a statement.
The FDA, in approving drugs, assesses them for safety and efficacy. CMS, in approving coverage, looks at whether a product is reasonable and necessary. Usually, the two line up.
The Medicare decision is widely seen as make or break for the beleaguered drug from the biotech company Biogen.
Several big health systems have refused to offer the drug, citing a lack of evidence on efficacy, and utilization has been extremely low. Biogen had eagerly sought approval by CMS. Medicare coverage is critical to increasing the use of the medication because about 80 percent of the patients who would be eligible are enrolled in the program. Private insurers often follow Medicare’s lead.
In a statement Tuesday, Biogen lamented the coverage proposal from CMS.
“This draft coverage determination denies the daily burden of people living with Alzheimer’s disease,” Biogen said. The agency’s proposal “will significantly limit patient access to an FDA-approved treatment, especially for underserved patients.”
Sean Tunis, former chief medical officer of CMS, said he was extremely surprised by the decision. Depending on the details of the clinical trials approved by CMS, he said, the number of people likely to get access to Aduhelm in the next few years would be hundreds, or maybe thousands.
“That’s a fraction of the total population of patients who would have met the FDA label requirement,” Tunis said.
Tunis said he thinks there is a disconnect between the FDA and CMS on drugs approved under the FDA’s accelerated approval pathway. That program is designed “to make therapies available while a confirmatory study is going on, and the CMS policy essentially negates that in this case. That seems like something that should be resolved.”
Jason Karlawish, a neurologist at the University of Pennsylvania, said the CMS announcement was good news.
“FDA made a mistake with its accelerated approval,” Karlawish said. “Most of the field has arrived at the conclusion. So in a sense, CMS is redressing that.”
The proposal is open to public comment for 30 days. The agency has said it plans to issue a final decision by April 11.
CMS officials said if Tuesday’s draft decision is made final in April, researchers would be able to apply to the agency for approval of trials right away. The officials emphasized that, to secure approval, researchers must pledge that they would enroll a group of patients that is diverse and representative of people in the Medicare program who have Alzheimer’s. To be eligible for coverage of the drug in a trial, patients must have mild cognitive impairment or dementia due to Alzheimer’s, with evidence of amyloid in the brain.
Aduhelm is a monoclonal antibody, a man-made protein that targets a sticky substance in the brain, called amyloid beta, which some scientists believe causes the memory-robbing disease. The drug, administered monthly as an infusion, is designed to trigger an immune response that reduces amyloid plaques.
Almost three years ago, Biogen halted two late-stage clinical trials after experts concluded the drug would not meet the goals of slowing cognitive decline and functional impairment. Several months later, in a surprise move, the company released additional data, asserting the drug could be effective at a high dose.
The FDA’s panel of outside scientific advisers rejected the argument in 2020, saying there was not evidence the medication worked. The FDA nevertheless approved the medication. The agency said there was a “reasonable likelihood” that reduction would benefit patients.
The FDA initially said all Alzheimer’s patients could receive the drug then narrowed that to people with mild cognitive impairment or early-stage disease.
About 6.2 million people in the United States have Alzheimer’s disease, according to the Alzheimer’s Association. But the number with early-stage or mild disease is much smaller. Biogen has estimated that only about 50,000 patients may initiate treatment in 2022, if Medicare and other insurers cover Aduhelm.
The therapy doesn’t cure Alzheimer’s disease or reverse it. The debate involves whether the drug slows cognitive decline by sharply reducing amyloid clumps. Some scientists are convinced that targeting amyloid will slow deterioration. Others say there is not evidence to support that — including from the Biogen trials.
“Most physicians don’t think it works,” said Lon S. Schneider, a psychiatrist at Keck Medical School of Medicine of the University of Southern California.
Mike Zuendel, a 67-year-old retired pediatric dentist who was diagnosed with mild cognitive impairment due to Alzheimer’s last year, was hoping for broad Medicare coverage for Aduhelm. He has had four infusions since September. So far, he has been billed for only the first infusion, but Medicare and private insurance has covered it. (In the absence of a national coverage policy, some regional Medicare administrators are paying for the drug on a case-by-case basis.)
“For me, and for a lot of other people, this is a life-or-death decision,” he said.
To some extent, the battle over the drug reflects an ongoing disagreement among doctors and researchers over the cause of Alzheimer’s disease. The amyloid hypothesis, which has dominated the field for decades, holds that toxic clumps in the brain, called amyloid beta, are the main driver of the disease and that removing them will slow cognitive decline. Aduhelm sharply reduces those clumps.
But years of testing drugs that target amyloid has yielded a string of failures, and many scientists have argued for a greater focus on other possible factors, including inflammation in the brain or damage to tiny blood vessels.
As part of its accelerated approval of Aduhelm, the FDA directed Biogen to conduct a follow-up trial to assess actual benefits — or the lack of them — to patients, with results due in nine years. Biogen said recently it was aiming to submit initial data in four years.
Aduhelm has had unexpected consequences.
In November, CMS announced a record increase, in dollar terms, for 2022 premiums for Part B, which covers outpatient services such as visits to the doctor. The increase was attributed partly to the need for a cushion for the potential high costs of the Alzheimer’s drug. But sales of the drug were lagging late last year, and Biogen cut the price of the drug almost in half, to $28,200.
On Monday, Health and Human Services Xavier Becerra ordered CMS to consider reducing the premiums for 2022. It is unprecedented to cut premiums after the year has started; usually, if calculations by the Medicare actuaries are off, adjustments in premiums are made in rates the following year.
CMS officials on Tuesday said they would not speculate on when the evaluation of premiums would be completed. They stressed that the Aduhelm decision did not take cost into account.