CMS Releases Unprecedented Memo Proposing Coverage of Alzheimer Drug Aducanumab be Limited to CMS-Approved Clinical Trials
In an unprecedented, proposed decision memo, the Centers for Medicare and Medicaid Services (CMS) suggest coverage by CMS for aducanumab (Aduhelm; Biogen, Cambridge, MA and Eisai, Woodcliff Lake, NJ) would not be covered outside of clinical trials approved by CMS. Aducanumab is the first potentially disease-modifying treatment of Alzheimer's disease (AD) to be approved by the Food and Drug Administration (FDA). Approval was granted via the accelerated approval pathway based on clinical trials showing dose- and time-dependent reductions in brain amyloid plaque in people with mild-to-moderate AD treated with aducanumab vs placebo.
This is the first time CMS has ever restricted coverage to participants in clinical trials approved by both CMS and the National Institutes of Health (NIH), neither of which are typically involved in approving clinical trials. If the decision is finalized in early April, after a public comment period ending on February 11, it will essentially deny coverage of an FDA-approved treatment. All but a select few thousand of the approximately 1.2 million people with mild-to-moderate AD covered by Medicare who could potentially benefit from aducanumab would not have access. Recent and historically large increases in Medicare Part B premiums had been partly justified by the potential high cost of covering AD treatments now that they are becoming available. Secretary for health and human services, Xavier Becerra, called for reexamination of the premium increase after a 50% price cut was announced for aducanumab. Whether such a re-examination will occur and how it might take the proposed highly restricted coverage into consideration has not been addressed by CMS.
Clinical development of aducanumab includes a history of starts and stops to clinical trials, making the risk-benefit analysis complex and long-term clinical benefits still unproven. In the EMERGE (NCT02484547) clinical trial aducanumab also reduced the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score by 22% for participants given the higher of 2 aducanumab doses after 78 weeks of treatment (n=547) compared with those given placebo (n=548) (P=.01). Statistically significant improvement was also seen on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 Items (ADAS-Cog 13; 27% versus placebo; P=.01), and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Inventory Mild Cognitive Impairment Version (ADCS-ADL-MCI; 40% versus placebo; P=.001). However, in the ENGAGE (NCT02477800) clinical trial, benefits to cognition did not reach statistical significance.
Serious side effects with aducanumab treatment include amyloid-related imaging abnormalities (ARIA), which occurred in approximately 40% of clinical trial participants treated with aducanumab. Although ARIA was typically asymptomatic and transient, it can be serious if brain swelling (edema) and microbleeds occur. Brain MRI before initiation and during treatment with aducanumab is required to monitor for ARIA, and there is ongoing debate regarding how often such imaging should be done.
Dr. Lee Fleisher, chief medical officer of CMS and director of its Center for Clinical Standards, said “While there may be the potential for promise with this treatment, there’s also the potential for serious harm to patients. This harm may include headaches, dizziness, falls, and brain bleeds. Our foremost goal is to protect beneficiaries from potential harm from an intervention without known benefits in the Medicare population. As a practicing physician, I cannot overemphasize the need to understand the risks and benefits of a given treatment in order to better inform patients and their families as they make decisions about their care.”
In response to the CMS draft decision memo, Harry Johns, chief executive officer of the Alzheimer's Association commented that "people living with AD deserve the same access to therapies given to those living with other conditions like cancer, heart disease and HIV/AIDS."
Johns described the draft decision as "shocking discrimination against everyone with Alzheimer’s disease, especially. . . women and Black and Hispanic people. . . (making) treatment available to a privileged few, those with access to research institutions, exacerbating and creating further health inequities." Johns further noted, "In issuing its decision CMS has the audacity to cite the Alzheimer’s Association 2021 Alzheimer’s Disease Facts and Figures report on the challenges and barriers underrepresented communities have in participating in clinical trials, and then turn around and propose to impose those very barriers."
Other drugs that lower brain amyloid plaque currently in development would also be affected by this decision.