A recent proposal that Medicare only cover Aduhelm (aducanumab) for Alzheimer’s patients participating in clinical trials is unnecessarily restrictive and will prevent many people from accessing a drug that could help them.

That’s the argument made by Jeffrey Cummings, MD, professor of brain health at the University of Nevada, Las Vegas. Cummings’ article, “Public Policy Should Drive Availability of Alzheimer’s Treatments: Comment on US Medicare’s Proposed Decision to Limit Payment of Aducanumab (Aduhelm) to Patients in Clinical Trialswas published in The Journal of Alzheimer’s Disease Prevention.

Aduhelm is an antibody-based therapy designed to clear the brain of irregular clumps of amyloid plaque proteins that are thought to contribute to the progression of Alzheimer’s disease.

Co-developed by Biogen and Eisai, the therapy received fast-track approval in June 2021 from the US Food and Drug Administration (FDA), which quickly changed its decision to specify that the drug should only be used at the start of the sickness. The approval was highly controversial, prompting members of an FDA advisory committee to resign and triggering a congressional investigation.

Early clinical trial data had shown that Aduhelm could remove amyloid plaques as expected. The FDA’s accelerated approval was based on this early data and required the drug’s makers to conduct additional clinical effectiveness testing.

The US Centers for Medicare and Medicaid Services (CMS) recently released a draft national coverage determination for Aduhelm and other drugs in its class. If approved, the decision would mean that Medicare, which provides health insurance for the elderly in the United States, would only help cover the cost of Aduhelm for patients taking the drug in clinical trials.

“This approach is not patient-centric and will significantly delay access to treatment for people with early AD [Alzheimer’s disease],” Cummings wrote.

Reduced efficiency, exaggerated security issues

Cummings says the draft coverage determination does not align with the FDA’s intention to grant expedited approval.

“The expedited approval aims to make the drugs available to patients with life-threatening conditions such as Alzheimer’s disease, while additional evidence confirming efficacy and safety is generated,” Cummings wrote, noting that this pathway is often used for other fatal diseases such as cancer.

“CMS’s decision to limit aducanumab to clinical trials is inconsistent with the intent of this approach and inconsistent with the FDA’s intent to provide a mechanism for expedited access to aducanumab for appropriate patients,” Cummings said.

Cummings argued that CMS’s proposal discounts evidence of Aduhelm’s benefit, but exaggerates safety concerns. Two large phase 3 trials found conflicting results on whether the Aduhelm treatment could slow a decline in cognition, which Cummings says may be partly explained by differences in dosage.

According to Cummings, the most optimistic interpretation of the available data on Aduhelm’s effect on cognition suggests that patients could be six years old in the early stages of dementia, rather than the more usual five. While he acknowledges that more research is needed to be sure of Aduhelm’s effect on cognition, “patients should be empowered to decide whether this degree of slowing is desirable for them,” Cummings wrote.

The main safety issue with Aduhelm is a form of brain swelling called ARIA, which occurred in more than a third of participants at the now approved dose of Aduhelm in trials. ARIA does not usually cause significant symptoms, although it can be serious, so monitoring is recommended during treatment.

Cummings wrote that the risks of ARIA posed by Aduhelm “do not exceed those of cancer therapies that are routinely covered by CMS.” He called the limitation of treatment coverage for AD patients “disease-based discrimination”.

“An approved treatment that could be available now”

Limiting Medicare coverage for Aduhelm only to trial participants would make the treatment less accessible, especially for traditionally underserved populations, Cummings said.

“Academic trial sites are rarely in minority neighborhoods and are not located to allow recruitment of rural populations (also underrepresented in clinical trials),” Cummings wrote. “Trials as proposed by CMS would require 1-2 years to secure funding plus 3-5 years to conduct and analyze, delaying the availability of an approved treatment that may be available now.”

The restrictions would also mean that people who can afford to pay for Aduhelm out of pocket will have access to the drug, while those who cannot will have to try to take part in clinical trials.

“Limiting treatment coverage to those on trial means that people in limited financial circumstances will have limited access to therapy, while those with financial means will have access to treatment. CMS requirements will increase inequity in AD care in the United States,” he wrote.

Cummings also noted that in many trials some participants receive an inactive placebo, so even participating in a trial does not guarantee that patients will have access to Aduhelm. And some may even end up paying for the placebo since the CMS usually doesn’t cover the full cost of the treatments.

There is also a higher proportion of white participants in US trials than in the general population. Cummings called the draft proposal’s requirement that all trials have a representative group of participants as a “lofty aspiration”, but not realistic given the difficulty of recruiting “underrepresented and underserved populations” for trials.

“We need to improve the inclusion of diverse populations in trials; this is a long-term goal requiring testing infrastructure not currently available and trust that has not been established,” he wrote. “Requiring a representative sample in the CMS trial will delay the trial and limit the availability of drug therapy for patients from minority and majority cultures.”

Cummings said he was also concerned that the CMS decision would stifle the pharmaceutical industry’s willingness to invest in potential Alzheimer’s therapies that would not be made reasonably available. He also noted that the CMS decision covering all amyloid-targeting antibody therapies fails to recognize the diversity of different therapies in this class that are under development, which could pose problems in the future.

The draft CMS proposal is available online. Public comments can be submitted online until February 10.