The Centers for Medicare and Medicaid Services issued a proposed decision memo detailing the coverage criteria for patients with Alzheimer disease to be covered by the federal health insurance platform when administered aducanumab (Aduhelm; Biogen).
The Centers for Medicare and Medicaid Services (CMS) has proposed that the government’s health insurance program will cover the administration of aducanumab (Aduhelm; Biogen) in the treatment of Alzheimer disease (AD) only for those patients who are partaking in CMS-approved randomized controlled trials that satisfy its coverage criteria, and those in trials supported by the National Institutes of Health (NIH), according to a recently published proposed decision memo.1
The 100 mg/mL intravenous injection was approved for use in Alzheimer disease in June 2021 with the accelerated pathway based on biomarker data, driving much discussion in the field about its potential efficacy and costs.2,3
Authored by a group including Joseph Chin, MD, MS, deputy director, Coverage and Analysis Group, and 6 others, the conclusion reached as it pertained to the clinical evidence of the monoclonal antibody (mAb) class was that “to date, no trial of an antiamyloid mAb has confidently demonstrated a clinically meaningful improvement in health outcomes (i.e., cognition and function) for AD patients. Thus, there is insufficient evidence to conclude that the use of monoclonal antibodies directed against amyloid is reasonable and necessary for the treatment of Alzheimer’s disease under §1862(a)(1)(A) of the Social Security Act.” As it pertains to aducanumab specifically, the group wrote that the “available evidence is insufficient to establish that the treatment is reasonable and necessary under section 1862(a)(1)(A) of the Social Security Act.”
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Chin and colleagues acknowledged that in the EMERGE trial (NCT02484547), there was a demonstration of “statistical significance of a primary health outcome in a post-hoc, secondary analysis of data for patients receiving high-dose aducanumab,” but noted that critical questions about the reliability of those results are lingering. “Our conclusion is that Biogen’s secondary analysis cannot overturn, definitively confirm, or substitute for, the RCT evidence,” they concluded.
CMS noted that to qualify for coverage, individuals included the NIH or CMS-approved trials must have a clinical diagnosis of mild cognitive impairment (MCI) due to AD or mild AD dementia, and evidence of amyloid pathology consistent with AD. As it pertains to the evidence of pathology, CMS will cover 1 amyloid-ß PET scan per patient if the patient did not previously receive such a scan. Patients must also not have any neurological or other medical condition that may significantly contribute to cognitive decline or likely to increase significant adverse events, nor an anticipated death from any cause during the duration of the study.
The trials themselves are also required to be conducted in a hospital-based outpatient setting and have a diversity of patients included that is representative of the national population diagnosed with AD, among a list of standards of scientific integrity (FIGURE). Additionally, they must address these questions:
The memo also notes that “a CMS approved randomized controlled trial may be extended to a prospective longitudinal study when the randomized controlled trial is completed, and the findings of the randomized controlled trial demonstrate a clinically meaningful benefit in cognition and function. Details of the prospective longitudinal study must be included in the same protocol as the randomized controlled trial.”
As it pertains to benefits and harms, Chin and colleagues concluded that there was “the lack of a clear clinical benefit and the frequency of adverse events like ARIA” did not provide supporting evidence benefits outweigh the harms this class of medication. “Adverse events are more closely monitored and treated in the context of a clinical trial compared to general practice. We have additional concerns at this time about harms in patients that would be treated outside the context of the safety monitoring of a controlled trial,” they wrote.
This news comes weeks after Biogen and Eisai announced an update on the status of the pending phase 4 study of aducanumab, dubbed ICARE AD (NCT05097131), stating that the final protocol for the post-marketing study will be submitted to the FDA in March 2022, and that the pair plans to initiate patient screening in May 2022.4 It also follows the announcement that the companies were reducing the wholesale acquisition cost from the previous price of $56,000 yearly to $28,200 yearly for the maintenance dose (10 mg/kg) for individuals of an average weight (74 kg), a reduction of 50.3%.5
The phase 4 placebo-controlled study is a post-marketing requirement of that accelerated approval pathway and is expected to enroll 1300 patients with early Alzheimer. The study’s design was originally announced during a late-breaking presentation at the 2021 Alzheimer’s Association International Conference (AAIC), July 26-30.6 Eisai and Biogen noted that they plan to continue to work with FDA, the external stakeholders, and other regulators around the world on the study design.