As members of the Patient, Consumer, and Public Health Coalition, we are providing these public comments on the National Coverage Analysis Proposed Decision Memo from the Centers for Medicare and Medicaid Services (CMS). This decision relates to coverage of Aduhelm and similar medical products for the treatment of Alzheimer’s disease.
We strongly support the CMS proposed decision to limit the coverage of these drugs to patients participating in clinical trials, because it will provide the evidence needed regarding safety and effectiveness for the Medicare population. We agree with CMS that this will enable patients and family members to make informed decisions based on unbiased information pertaining to the known risks and as yet unproven benefits.
The Food and Drug Administration’s (FDA) approval of Aduhelm (aducanumab) has generated unprecedented controversy. The clinical trials that the manufacturer, Biogen, submitted to the FDA did not meet FDA standards of safety and efficacy, resulting in a unanimous vote against Aduhelm by the FDA’s Advisory Committee. Committee members expressed concern that the drug was not proven to improve memory or cognition, but it did cause brain swelling, brain bleeds, nausea, headaches, dizziness, confusion, and an altered mental state in approximately half the patients.
Unfortunately, FDA approved Aduhelm on the basis of a biomarker that is associated with Alzheimer’s but that previous research has shown does not predict improved memory or cognition.1
It is especially concerning that fewer than 4% of the patients in the Aduhelm clinical trials were Black or Hispanic, making it impossible to determine safety of efficacy for those populations. In addition, the trials excluded patients who were over the age of 85, as well as individuals with numerous chronic conditions that are common in Medicare beneficiaries, such as heart disease, blood clots, kidney disease, impaired liver function, and individuals taking blood thinner. In fact, the data from the Aduhelm studies were based on patients representing a small minority (15%) of the types of Medicare beneficiaries who have mild cognitive impairment.
We make the following recommendations as CMS finalizes the coverage decision and develops the clinical trial guidance:
- CMS needs to describe the mechanisms in place to enforce their requirements for diversity.
Biogen has claimed that the CMS decision would limit access to Aduhelm by people of color. However, since the company’s studies had few people of color, it is the company that is at fault for not establishing the safety or efficacy of Aduhelm for people of color.
Fortunately, CMS’s proposal addresses that problem, by mandating that CMS-funded trials must include a nationally representative population of people with Alzheimer’s disease. We urge that this diversity include a substantial number of patients in different racial, ethnic, and age groups to ensure that there is enough statistical power for subgroup analyses to determine safety and efficacy for each of the major demographic groups. CMS should also explain how they will ensure that the study participants represent the co-morbidities typical of Alzheimer’s patients, while protecting patients who might be less likely to benefit. Since CMS plans to restrict clinical trials to the most appropriate treatment centers, CMS should specify how that and other strategies will help ensure the diversity that is needed.
- Protecting Patients from Adverse Effects.
There are significant safety concerns associated with Aduhelm. In the original clinical trials 41% of patients experienced brain swelling or brain bleeds.2 Other side effects included headaches, nausea, dizziness, confusion, and an altered mental state. The final CMS coverage decision should be very explicit about how they will protect clinical trial participants, and how they will ensure convenient, free access to brain scans and other safeguards.
- Drug manufacturers should share the cost of these CMS clinical trials.
Biogen is charging $28,000/patient/year for Aduhelm, which is an outrageous price for an unproven drug. In addition, Aduhelm requires numerous brain scans to determine the presence of amyloid plaques on the brain and possible brain swelling. Biogen should reduce the cost of Aduhelm in the trials and share the costs of brain scans and administrative fees. These costs should be made publicly available.
- CMS should be consistent in its coverage for similar Alzheimer’s treatments that are not proven to improve memory or cognition.
FDA’s decision to approve Aduhelm despite no clinical evidence of benefit has persuaded several other companies to submit applications to FDA based on similarly weak evidence of efficacy. CMS’ proposal should apply to all Alzheimer’s drugs that fail to provide solid evidence of clinical benefit, requiring well-designed clinical trials representing the diversity of Medicare beneficiaries.
We strongly support the CMS proposed plan, which will protect Alzheimer’s patients, reduce the financial burden on all Medicare beneficiaries, while also helping to keep the Medicare program solvent.
We appreciate the opportunity to provide insight into this decision and strongly encourage CMS to consider our recommendations aimed to protect patients, consumers, and the public health.
ORGANIZATIONAL SIGN ONS
American Medical Student Association (AMSA) UW Madison Chapter
Doctors for America
Jacobs Institute of Women’s Health
National Center for Health Research
National Organization for Women
National Women’s Health Network
Our Bodies Ourselves
Patient Safety Action Network
USA Patient Network
Washington Advocates for Patient Safety
- Zuckerman, D.M., Jury, N.J., Silcox, C.E. (2015) 21stCentury Cures Act and similar policy efforts: at what cost? BMJ ;351:h6122 doi: 10.1136/bmj.h6122
- Salloway, S., Chalkias, S., Barkhof, F., et al. (2021) Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease. JAMA Neurol ;79(1):13–21. doi:10.1001/jamaneurol.2021.4161