UsAgainstAlzheimer’s, Experts Blast Medicare’s Plan for Aduhelm

A recent proposal to limit Medicare coverage for Aduhelm (aducanumab) and similar medicines to Alzheimer’s disease patients who are enrolled in clinical trials ignores current science and would drastically curtail access these therapies, UsAgainstAlzheimer’s argues.

UsAgainstAlzheimer’s (UsA2), based in Washington, D.C., is founded by family members of people affecting by Alzheimer’s.

Its comment letter was in response to a draft National Coverage Determination proposed by the U.S. Centers for Medicare and Medicaid Services (CMS). If enacted, the proposal would effectively mean that Medicare, the government-funded health insurance program for the elderly, would only help cover the cost of Aduhelm and similar medicines — monoclonal antibodies directed against amyloid plaques — for patients in clinical trials.

UsA2 wants CMS to support the use of approved medications by patients as recommended by the U.S. Food and Drug Administration (FDA).

“UsAgainstAlzheimer’s is filing our comments today expressing in the strongest terms the devastating effects of CMS-proposed coverage decision,” George Vradenburg, the group’s chairman and co-founder, wrote.

“Our government’s proposal seems to be saying ‘Medicare is for all seniors, except Alzheimer’s patients.’ This draft plan could deny patient access to these treatments for a decade,” Vradenburg said. “Patients cannot afford for this proposed decision to stand, and we will use every means at our disposal to reverse this unconscionable anti-patient decision.”

A group of 64 clinicians and researchers specializing in Alzheimer’s expressed similar concerns in a joint comment. CMS “must base its decisions on an accurate, up-to-date understanding of the science; must not prejudge the outcome of the scientific process; and must allow patients and their doctors to make informed choices,” they wrote.

Biogen, which co-developed Aduhelm with Eisai, also called on the CMS to change the proposal.

“We remain steadfast in our commitment to patient choice and urge CMS to provide coverage for FDA approved treatments,” Maha Radhakrishnan, MD, Biogen’s chief medical officer, said in an email to Alzheimer’s News Today.

Demands duplicate ‘FDA-mandated trials’

Aduhelm, a monoclonal antibody (mAb), is designed to break up amyloid plaques (irregular clumps of protein in the brain) that are characteristic of Alzheimer’s and thought to drive the disease.

In clinical trials, Aduhelm consistently lowered plaque levels, though results of two large trials were inconsistent as to whether that could slow a decline in cognition and function. According to researchers, this inconsistency may be attributable to dosing differences among the trials.

The FDA gave Aduhelm accelerated approval in 2021, and quickly amended its decision to specify that the medication’s start should be in those with mild disease.

Accelerated approval, based on early clinical data showing Aduhelm could clear amyloid plaques from the brain, carries with it a requirement for additional testing to clarify the effect on cognition and function. Work on a Phase 4 trial is now in progress.

“Aduhelm, like all accelerated approval drugs, is subjected by the FDA to a confirmatory study requirement, which will adhere to FDA’s well-established standards,” Biogen stated in its comments.

According to Biogen, a Medicare requirement to cover Aduhelm only for patients in trials “would either duplicate or undermine robust efficacy and safety data collection efforts already in place, inappropriately duplicate and replace FDA authority, and unnecessarily restrict coverage.”

Efforts to collect real-world data, such as patient registries, would also be affected, the company added. Such data could allow for meaningful assessments of the therapy’s effectiveness outside the restrictive context of a trial.

UsA2 and the clinicians/researchers also echoed arguments that these requirements duplicate efforts already in place and go against FDA reasoning in providing accelerated approval.

“This approach usurps the authority of the FDA, confuses evidentiary standards, sets an unsupportable precedent in determining what is reasonable and necessary for a Medicare beneficiary, and puts patients awaiting access to Aduhelm or other promising mAbs on notice that, for them, the door is shut,” the UsA2 stated.

“Rather than requiring new [clinical trials], we encourage CMS to consider how patient registries, claims data, electronic health records, and ongoing regulatory trials could be leveraged to develop more-robust evidence on the safety and effectiveness of anti-amyloid immunotherapy,” the researchers wrote.

A ‘non-coverage’ decision

According to UsA2, CMS’s proposal “will prevent nearly every American who might benefit from a mAb from accessing one of these treatments for a decade or more.”

“We should call this decision what it is: it is a ‘non-coverage’ decision,” UsA2 wrote.

Effectively, only people wealthy enough to pay for Aduhelm out-of-pocket would be able to access the therapy, while everyone else would be limited to competing for slots in clinical studies.

“We estimate that only about 50 hospital locations in the entire country are capable of running the types of trials CMS proposed, so only people fortunate enough to live near one of those sites could feasibly secure one of the estimated 1,500 slots available,” UsA2 stated.

Clinical trials also take time and resources to design and implement; it is common for the process between starting a trial’s design and starting to dose participants to take years. Plus, some trial participants are assigned to a placebo, there’s no guarantee those enrolled will be treated.

Another concern is that clinical trials historically enroll whites in disproportionate numbers, although Alzheimer’s in the U.S. disproportionately affects Blacks and Latinos/Latinas.

“Despite CMS’s stated commitment to representativeness, the [proposal] is likely to continue to cement these disparities into the CMS-directed trial design,” UsA2 stated.

The organization noted that about 1,000 patients every day progress from early to later disease stages — where they would no longer be eligible to start using Aduhelm.

“The math is simple, and the result is irrefutable. By the decision, the government would be consigning millions of Americans to inevitable decline and death, with no possibility of appeal,” UsA2 stated. “It is inhumane to deny patients who meet the label criteria the choice of whether to use this or other future, FDA-approved drugs in the class.”

‘Misunderstanding’ of the science

One concern raised by CMS is a lack of evidence that lowering amyloid beta plaques in the brain will translate into a clinical benefit for Alzheimer’s patients. The researcher and clinician group argues that this is based on “a misunderstanding of the state of the science.”

“CMS’s concern that [amyloid beta] clearance is not reasonably predictive of clinical benefit relies on older studies of drugs that are not equivalent to this new generation of medications,” they wrote.

Older medications have not been shown to break up amyloid plaques, they wrote, as have Aduhelm and other more recent, potential therapies.

“Plaques have been linked by many observations to cognitive impairment in [Alzheimer’s], and the effect of mAbs on plaques meets the standard of ‘reasonably likely’ to predict clinical benefit,” Jeffrey Cummings, MD, a professor of brain health at the University of Nevada Las Vegas and one of the scientists in the joint comment, wrote in a recent paper.

Biogen noted that the CMS draft decision “mentions in passing that there are key differences between the first and second generation of products but proceeds to include masses of trial data from first generation products … while not mentioning supportive data from second-generation” anti-amyloid therapies that were key to the FDA’s accelerated approval.

Another point of contention is that the CMS’s draft decision wouldn’t just apply to Aduhelm, but to therapies in the same class that may yet be approved.

“While it is true that the drugs under discussion are all monoclonal antibodies that target amyloid beta in the brain, they are not equivalent drugs,” the researchers wrote, stressing differences in their mechanisms of action and safety profiles.

“It is not scientifically sound to prejudge the risk–benefit profiles of drugs that are still undergoing development and evaluation based on their membership in a broad class, only one example of which has received FDA approval,” the researchers wrote.

Overall, the draft decision “is anti-patient, anti-science, and anti-Food and Drug Administration,” UsA2 said.

“We urge CMS in the strongest of terms to revise this draft determination to provide coverage to label for FDA-approved monoclonal antibodies (mAbs) in this class.”