24 Policy
Pharmacy Practice News • May 2022
FDA Watch
CMS Issues Final Aducanumab Coverage Decision By Gina Shaw
T
he Centers for Medicare & Medicaid Services (CMS) finalized its Medicare coverage policy for the controversial Alzheimer’s disease drug aducanumab (Aduhelm, Biogen) on April 7, 2022. As in the initial plan released in March, aducanumab will be covered for Medicare recipients under the “coverage with evidence development” (CED) guidance, meaning the drug will only be covered in the setting of a clinical trial. However, the final proposal contains several key changes from the original draft. Coverage is expanded beyond the original proposal, which included only CMSapproved randomized controlled trials. Instead, Medicare will cover the drug for participants in any trial approved by the FDA or the National Institutes of Health. “The final decision allows for flexibility in a less rigorous study design for antiamyloid mAbs [monoclonal antibodies] that
other populations who were excluded from eligibility for CED coverage in the original proposal will be eligible for trial participation and coverage under the final policy. The trials also must comply with a Medicare requirement to recruit a racially and ethnically diverse group of participants; most participants in the original EMERGE and ENGAGE trials of aducanumab were white. Finally, any future FDA-approved mAbs targeting amyloid will not automatically be subject to the same CED policy, as proposed in the draft policy. For drugs that follow the FDA’s traditional approval pathway, patients will not need to be enrolled in a randomized trial to have the drug covered by Medicare, according to CMS; instead, they can be in a registry-based study, which does not require a placebo arm. (Drugs that go through the same accelerated approval pathway as aducanumab will be subject to the same clinical trial requirements.)
‘While [aducanumab] is known to reduce amyloid plaques in the brain, there is no [currently available] evidence that this leads to clinical benefit in the form of improved cognitive function.
have been approved by FDA through the traditional approval process for the treatment of AD,” CMS noted in a statement. These trials are not restricted to hospital-based outpatient facilities, as in the original proposal, and can be conducted in other sites such as freestanding outpatient infusion centers and physician practices. The coverage decision does require that “any clinical study protocol submitted for CMS-approval include a description of the multidisciplinary dementia team and optimal medical management, and the study sites with clinical expertise and infrastructure to provide treatments consistent with the safety monitoring outlined in the FDA-approved label.” People with Down syndrome and
“CMS wants to support the development of and access to innovative therapies that provide reasonable and necessary treatments to Medicare patients,” said Tamara Syrek Jensen, JD, Director of the Coverage and Analysis Group in the Centers for Clinical Standards and Quality at CMS, in a public call with stakeholders on April 11, 2022, explaining the rationale behind the two coverage pathways. “The second pathway allows for a wider array of studies for drugs that receive traditional approval, such as data collection in a registry.” Ms. Jensen added that the approach was “tailored to drugs in this class” and would not affect CMS’ decisionmaking about other drugs approved via the FDA’s accelerated approval pathway.
“This is an evolving area and we intend to be nimble and flexible as new evidence is developed,” she said. “We can reconsider our coverage with evidence development decisions, and have done so in the past when appropriate.” “This unprecedented CMS decision effectively denies all Medicare benefi-
importance of remembering the original scope of aducanumab’s approval. The drug “was approved for mild cognitive impairment, meaning that it is directed at patients who are recently healthy and may not have outward signs of dementia,” he said during the stakeholder call. “There may be potential for promise
‘Under extraordinary pressure from many different sides, they have made an evidence-based decision that doesn’t abandon the notion that we need to understand if drugs are safe and effective before they’re used and covered.’ —Caleb Alexander, MD ciaries access to Aduhelm,” Biogen said in a statement. “These coverage restrictions, including the distinction between accelerated approval and traditional approval, have never been applied to FDA-approved medicines for other disease areas.”
‘Evidence-Based Decision’ Caleb Alexander, MD, a professor of epidemiology and medicine at Johns Hopkins Bloomberg School of Public Health and the co-director of the Johns Hopkins Center for Drug Safety and Effectiveness, in Baltimore, told Pharmacy Practice News that CMS had threaded the needle fairly well under difficult circumstances. “Under extraordinary pressure from many different sides, they have made an evidencebased decision that doesn’t abandon the notion that we need to understand if drugs are safe and effective before they’re used and covered, and that’s exactly what we need for a question that is as important as this one to get right,” said Dr. Alexander, who serves on the FDA’s Peripheral and Central Nervous System (PCNS) Drugs Advisory Committee, which recommended in November 2020 that the agency not approve aducanumab. “They will evaluate the next products on their own merits, which will obviously require more work on the part of CMS, but it’s the right decision. There may be important differences in how these products work, as well as in the totality of evidence regarding their safety and effectiveness. This approval was highly atypical in many ways, and I think the FDA is unlikely to approve another product based on evidence that is as flimsy as this was.” Lee Fleisher, MD, the chief medical officer and director of CMS’ Center for Standards and Quality, underscored the
with this treatment; however, while it is known to reduce amyloid plaques in the brain, there is not currently evidence that this leads to clinical benefit in the form of improved cognitive function. Meanwhile, the known risks include potentially fatal brain bleeds. Taken together, there is not yet sufficient evidence to support coverage of this drug for people with Medicare until the statutory ‘reasonable and necessary’ standard is met.”
A History of Concern Although patient advocacy groups have been lobbying for a more favorable aducanumab coverage determination, several managed care and provider stakeholders have long been on record urging far more restraint. In July 2021, for example, at least three major hospital systems—Cleveland Clinic in Ohio, Mount Sinai Health System in New York, and Providence Health in Washington state—announced they will not provide aducanumab, although affiliated physicians could, at least in theory, prescribe it for their patients to receive it elsewhere. At the time, the Neurology Center, a leading independent neurology group with seven locations in Washington, D.C., and Maryland, also announced that it would not be providing aducanumab. Pushback also has come from several commercial plans, with several announcing that they will not cover aducanumab, including Blue Cross Blue Shield affiliates in Florida, Kansas, New York, Michigan, North Carolina and Pennsylvania. Policies posted online indicated that these payors were denying coverage because they considered the drug “investigational” or “experimental” or because “a clinical benefit has not been established.” The sources reported no relevant financial disclosures.
