The Centers for Medicare & Medicaid Services (CMS) will cover the controversial drug aducanumab (Aduhelm) for the treatment of Alzheimer disease only if patients are enrolled in a qualifying clinical trial, the agency announced last week.
This proposed CMS National Coverage Determination, which is expected to be finalized in April after a public comment period ending in mid February, would sharply limit the number of patients with Alzheimer disease who could use the medication. The decision would also apply to similar monoclonal antibody–based drugs that target amyloid beta and are currently in clinical trials.
“CMS has proposed an evidence-based coverage policy after experts reviewed all relevant publicly available evidence and feedback received from stakeholders,” CMS Administrator Chiquita Brooks-LaSure, MPP, said in a statement. Reports in the media noted that the decision appears to be the first time that CMS has restricted access by Medicare beneficiaries to a drug approved by the US Food and Drug Administration (FDA).
The FDA approved aducanumab in June 2021, based on the surrogate end point of reducing amyloid beta plaque in the brain, on an accelerated approval pathway.
In its announcement of the drug’s approval, the FDA said this pathway is “intended to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit.” Acknowledging the uncertainty about the drug’s effectiveness, the agency required a postapproval clinical trial to verify actual clinical benefit.
However, The FDA’s decision to approve the drug was widely criticized by researchers and clinicians. Many noted that the drug’s approval ran counter to the recommendations of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee of independent experts.
At a November 6, 2020, meeting, 10 of the 11 committee members recommended that the agency not approve aducanumab, with the remaining member “uncertain.”
Besides characterizing the evidence that aducanumab could slow cognitive decline in people in the early stages of the disease as unconvincing, the committee also noted that the drug, which is given as a monthly infusion, can cause potentially serious adverse effects, notably brain edema and brain hemorrhage.
Brain edema or bleeding occurred in about 40% of participants who received the currently approved dose of aducanumab in clinical trials. The drug’s labeling warns about these potential adverse effects and advises monitoring patients and having them undergo 2 magnetic resonance imaging scans during the first year of treatment.
Researchers also have noted that clinical trials of aducanumab would have excluded the vast majority of Medicare beneficiaries with Alzheimer disease and related disorders and those with mild cognitive impairment on the basis of their age or other conditions. The increased risk of brain edema and bleeding seen in the clinical trials is likely to be higher in patients who would been ineligible for the trials, especially patients who had previously experienced a stroke or those with chronic conditions treated with drugs that themselves increase the risk of bleeding.
After the FDA approved aducanumab—with a requirement that Biogen conduct a postapproval clinical trial to verify clinical benefit—3 of the advisory committee members took the unusual step of resigning in protest of the FDA’s decision.
The drug’s hefty cost—which Biogen initially priced at $56 000 a year—also sparked controversy, given the drug’s uncertain benefits. Use of aducanumab has the potential to result in enormous costs overall, burdening the Medicare system, leading to increases in Medicare premiums, and resulting in patients incurring out-of-pocket coinsurance costs of up to $11 500 annually.
In fact, CMS announced a proposed increase in the monthly Medicare premium for Medicare Part B in 2022 of at least $21.60, one of the largest increases in recent years, with that increase partly stemming from the need to maintain “contingency reserves” related to potential coverage of aducanumab. After Biogen announced it was reducing the price to $28 200 per year—after sluggish uptake of the drug—Department of Health and Human Services Secretary Xavier Becerra announced that he was instructing CMS to reassess the recommended boost in premiums.
“With the 50% price drop of Aduhelm on January 1, there is a compelling basis for CMS to reexamine the previous recommendation,” he said.
A number of major hospitals and health care systems—including the Cleveland Clinic, Mount Sinai Health System in New York City, the US Veterans Health Administration, and others—have announced that they will not offer aducanumab. Also, several regional health insurance plans, including Blue Cross Blue Shield in Kansas, Massachusetts, Michigan, New York, North Carolina, and Pennsylvania, have said they will not cover the drug.
If the proposed National Coverage Determination is finalized, CMS “will review each submitted clinical trial to determine whether it meets specific criteria,” the agency said. Medicare patients participating in these trials would be eligible to receive coverage of the drug, related services, and other routine costs, which may include positron emission tomography scans.
In addition to trials approved by CMS, clinical trials sponsored by the National Institutes of Health would be covered under the determination.
To meet the agency’s requirements for approval, clinical trial participants must have a clinical diagnosis of mild cognitive impairment due to Alzheimer disease or mild Alzheimer disease dementia and have evidence of amyloid in their brains as determined by a positron emission tomography scan. The trial also must be conducted in a hospital-based outpatient setting.
In addition, CMS proposed as a trial requirement that “the diversity of patients included in each trial must be representative of the national population diagnosed with [Alzheimer disease].” Although Black and Hispanic individuals are more likely to develop Alzheimer disease compared with their White counterparts, previous clinical trials were hampered by a lack of diversity among study participants.
Some patient advocacy groups, such as the Alzheimer’s Association, expressed disappointment in CMS’s preliminary decision and vowed to lobby Congress and pressure CMS to cover the drug. The agency said that after it reviews comments on the proposed determination, it will announce its final decision by April 11, 2022.
Published: January 20, 2022. doi:10.1001/jamahealthforum.2022.0048
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Stephenson J. JAMA Health Forum.
Corresponding Author: Joan Stephenson, PhD, Consulting Editor, JAMA Health Forum (Joan.Stephenson@jamanetwork.org).
Conflict of Interest Disclosures: None reported.
Stephenson J. Medicare to Cover Controversial Alzheimer Disease Drug Only in Clinical Trials. JAMA Health Forum. 2022;3(1):e220048. doi:10.1001/jamahealthforum.2022.0048
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