Medicare coverage of aducanumab for Alzheimer’s disease: the impact of the decision

With a growing aging population, the prevalence of Alzheimer’s disease (AD) in the United States is expected to reach 14 million by 2060. ¹ This figure represents an increase of more than 8 million cases from the current estimated rate of 5.8 million, according to the Centers for Disease Control and Prevention (CDC). These trends underscore the critical need to develop treatments that can reduce the severity of symptoms associated with AD.

Anti-amyloid antibodies have been the subject of several clinical trials in recent years, in the hope that these therapies may reduce cognitive impairment in patients with AD. In June 2021, despite mixed results in clinical trials, aducanamab (Aduhelm), a monoclonal antibody, became the second drug approved by the US Food and Drug Administration (FDA) for the treatment of AD since 2003.^2.3

Aduhelm received approval through the FDA’s accelerated approval pathway rather than the traditional clinical approval pathway based on demonstrated clinical benefit. With the fast track, approval is based on a surrogate endpoint – in the case of Aduhelm, a reduction in amyloid-beta plaque as shown on positron emission tomograms (PETs).

Several other anti-amyloid antibodies are currently being studied in Phase 3 clinical trials, including gantenerumab (Clinicaltrials.gov Identifier: NCT05256134), lecanemab (Clinicaltrials.gov Identifier: NCT03887455), and donanemab (Clinicaltrials.gov Identifier: NCT05026866). It is expected that the results of these trials will be announced within the next year.⁴

In April 2022, the US Center for Medicare and Medicaid Services (CMS) finalized its decision on Medicare reimbursement for this class of drugs, with coverage restricted to participants in CMS-approved prospective comparative studies only.⁵ In addition to Aduhelm, which costs around $28,000 (down from the original price of $56,000 per year) for “average weight” patients (163 pounds), the CMS decision also applies to drugs. antiamyloids that may receive FDA approval in the future, including those approved through the traditional route.⁶

While some experts in the field expressed support for CMS’s position, others criticized the decision to subject anti-amyloid drugs to the ‘coverage with development of evidence’ (CED) mechanism. For example, Paul Aisen, MD, founding director of the Institute for Therapeutic Research in Alzheimer’s Disease at the University of Southern California, called it “essentially a non-coverage decision.”^seven

In an August 2022 comment published in JAMA Neurology, Stern and Selkoe said that this measure has never applied to any other drug and therefore discriminates against people with Alzheimer’s disease. “CMS has apparently decided that the evidence required to cover the treatment of patients with Alzheimer’s disease must meet a higher standard than the evidence required for any other patient,” they wrote.³

To discuss the impact of Medicare’s decision to cover Aduhelm only for Medicare beneficiaries participating in research, we spoke with Maria Glymour, ScD, MS, a researcher specializing in cognitive aging, Alzheimer’s disease, and dementia, and professor in the department of epidemiology and biostatistics at the University of California, San Francisco, School of Medicine.

What is your position on FDA approval of Aduhelm?

Glymour: To date, there is no convincing evidence that Aduhelm can improve the memory or well-being of people with [AD]. The consequences of common side effects are unclear and can be very harmful. Given the lack of conclusive evidence of benefit and serious concerns about harm, as well as the clearly unrepresentative studies, FDA approval was not warranted.

CMS has decided to restrict Medicare coverage to Medicare beneficiaries who participate in research for Aduhelm and future amyloid antibodies. How does this affect all AD patients?

Glymour: Our top priority should be to identify effective drugs to prevent and treat Alzheimer’s disease, and Medicare’s decision will make that happen faster. It was a pro-patient decision, and the day we have effective drugs, I think we can thank Medicare for helping us get there faster. Why? ‘Cause Medicare said, in effect, they won’t pay for a drug that doesn’t actually help. [patients with AD]; if companies want Medicare coverage, they need to find a drug that is actually useful. It’s not enough to develop a drug that changes a biomarker but doesn’t help people remember better, think better, or function better. We need to find a medicine that makes a difference in people’s lives.

Do you believe that the CMS decision discriminates against AD patients?

Glymour: It is not discriminatory against people living with AD to require effective medication. The Stern and Selkoe article⁴ is quite misleading about the regulatory burden placed on anti-amyloid drugs approved on the basis of their clinical efficacy – if such drugs are ever identified. The Medicare ruling made a major distinction between future anti-amyloid treatments that are approved on the basis of helping patients and those approved without evidence that they improve symptoms or slow disease progression.

The Medicare decision was structured to facilitate access to anti-amyloid drugs that have been shown to have clinical benefits, if approved, simply requiring participation in a registry for coverage of these drugs. It maintains a higher standard for anti-amyloid drugs approved without clear evidence of clinical benefit – like Aduhelm – to ensure that we learn more about the harms and benefits quickly. It’s common sense, not discrimination.

What is the potential impact of Medicare’s decision regarding Aduhelm on the status of the FDA’s fast-track approval pathway in general?

Glymour: I don’t know what the impact will be on the FDA. More importantly, I hope this sends a message to the companies developing these drugs that they need to demonstrate clinical benefit. It was quite painful to watch Biogen roll out a flashy ad campaign for a drug with no clear evidence of benefit.

What measures are needed to increase access to Aduhelm and future anti-amyloid antibodies with traditional FDA approval?

Glymour: The biggest challenge right now is finding a drug or other treatment that actually improves the lives of people living with AD. Once there is a drug that really works and is safe for everyone, access will be a high priority. Obviously, a lower price than Biogen has put on Aduhelm would help with access. Inclusive trials, so that people of all racial and ethnic identities can be confident that trial evidence is relevant to them, would also help.

What actions can help bring effective anti-amyloid drugs to market faster?

Glymour: Right now, today, big companies like Biogen, Eli Lilly, and Roche already have valuable information that could help us evaluate these drugs and accelerate progress, but they’re not using it because they should be sharing data with each other instead of competing with each other. If companies shared data, then we might see patterns that we can’t see in a single study.

Advocacy groups like the Alzheimer’s Association should hold companies accountable for prioritizing faster research instead of prioritizing competition over each other. Part of that responsibility would be meaningful data sharing to determine whether certain groups of people benefit from anti-amyloid drugs.

If companies got together and collaborated — even with the data they’ve already collected — we’d learn a lot more about these drugs, who might benefit from them, and their long-term consequences. It’s very frustrating to me because until we insist that companies collaborate and share data, we won’t do everything we can to end [AD].