In the context of the Centers for Medicare and Medicaid Services’ (CMS) final coverage decision on amyloid beta-targeting monoclonal antibodies for Alzheimer’s Disease, stakeholders are seeking to understand how the CMS coverage policy will impact future access not only for Alzheimer’s Disease therapies but also for other novel agents in therapeutic areas of unmet need, especially those approved under the Accelerated Approval pathway.

Details

On April 7, the CMS released the final national coverage determination (NCD) with coverage with evidence development (CED) on Food & Drug Administration (FDA)-approved anti-amyloid monoclonal antibodies (mAbs) for the treatment of Alzheimer’s disease (AD). Specifically, the NCD limits Medicare coverage for this class of drugs to beneficiaries in FDA-approved randomized controlled trials, CMS-approved studies, or studies supported by the National Institutes of Health depending on the evidence that was used for FDA drug approval.

The final NCD is the culmination of a national coverage analysis process that commenced in June 2021. The coverage policy would apply to all current and future monoclonal antibodies directed against amyloid plaque. The NCD with CED states that beneficiaries must have a clinical diagnosis of mild cognitive impairment due to AD or mild AD dementia, with confirmed presence of amyloid beta pathology consistent with AD, to be eligible to receive mAb treatment via an approved randomized controlled trial or other study. This population aligns with that specified on the FDA label for the only product approved to date, Aduhelm. However, the CMS stated that any future FDA label updates may lead to reevaluation of the coverage policy accordingly. Anti-amyloid mAbs approved based on evidence of efficacy from a change in a surrogate endpoint may be covered under approved randomized controlled trials, whereas those approved based on evidence of efficacy from a direct measure of clinical benefit may be covered under approved prospective comparative studies, including ones in real care settings.

The final NCD with CED removed exclusion criteria related to comorbidities or cognitive conditions, thus slightly expanding the number of beneficiaries who may be eligible for treatment. The requirement to conduct approved trials in the hospital outpatient department setting was also removed in response to stakeholder comments that the requirement would restrict access for beneficiaries in underserved areas. However, the final NCD with CED still requires study sites to staff multidisciplinary dementia teams, which may limit certain providers’ ability to participate.

Key Considerations for Stakeholders

Despite the broadening of patient eligibility criteria and sites of care from the draft decision, the CMS’s final coverage policy for anti-amyloid mAbs for treatment of AD retains the CED requirement, so access barriers in this therapeutic area are likely to persist. The twofold coverage dynamics based on the FDA approval pathway also signal how the CMS may treat uncertainty and quality of evidence in future coverage determinations in therapeutic areas of unmet need. Stakeholders should be aware of the implications that drug approval pathways may have on CED requirements and the potential impact for patient access to treatment.

Providers

The provider community must prepare for the operationalization of a clinical trial or registry including supporting patient selection and enrollment, data reporting, documentation, and claims submission requirements. To address the CED requirements, providers may need to adapt current operations and coordinate closely with other involved stakeholders (e.g., the CMS, manufacturers, patients, professional societies). Providers’ ability to participate in trials that meet CMS requirements in an expedient fashion will be critical to ensuring timely and appropriate access to Medicare beneficiaries. These challenges will be heightened at a time in which many providers are focused on adequate staffing and operations throughout the public health emergency and shortage of healthcare resources.

Manufacturers

While the CMS stated that it will be monitoring future developments in this class of treatments, it remains unclear whether the NCD process will be flexible enough to accommodate rapid advances in this developing field. As manufacturers review the final NCD, understanding CMS coverage decisions will shape future commercialization planning for novel therapies. In particular, regulatory approval pathways and evidence development strategies may shift towards ensuring both FDA and CMS regulatory and coverage priorities are met. This balance will require a market access strategy that includes early collaboration and engagement across multiple stakeholders including patient advocacy and professional groups in addition to regulatory agencies.

Patients

While the CED aims to offer appropriate access for patients interested in innovative therapies and technologies, the nature of the CED may also restrict patient access. Under the final NCD for AD mAbs, coverage for treatment requires enrollment in a clinical trial or registry, which will inherently limit patient access. With greater coverage restrictions, social determinants are likely to have higher impact on access to the treatment. Patient groups have expressed concerns that in the past, when Medicare placed a CED requirement, coverage was largely restricted to beneficiaries who live close to or can travel to participating trial sites. Avalere has previously analyzed potential implications for rural and underrepresented populations.

Payers

While the NCD will be directly applicable to Medicare Part B, it will have implications for a broader set of payers:

• Medicare Advantage (MA): For NCDs requiring CED, MA plans are responsible for payment of both items and services in approved CED trials and studies immediately, unless the CMS determines that an item or service exceeds the significant cost threshold. If the significant cost threshold is met, then Medicare Fee for Service would cover the item or service until the next MA plan rates are set. The CMS has not released whether the final NCD with CED has met the significant cost threshold.
• Medicare Part D: If an anti-amyloid mAb is not covered by Part B under the terms of the NCD, the drug would meet the definition of a Part D drug. However, because the drug was deemed not reasonable and necessary by Medicare Part B, standalone Part D and MA prescription drug plans could elect to exclude the drug from Part D coverage.
• Dual-Eligible Beneficiaries: If the drug is not covered by Medicare Part B under the terms of the NCD and the drug is deemed eligible for Part D, Medicaid is not required to cover the drug for dual-eligible beneficiaries.
• Medicaid: State Medicaid programs are required to cover the drug for Medicaid-only beneficiaries if a manufacturer has a National Drug Rebate Agreement in place with the Department of Health & Human Services. State Medicaid programs may leverage utilization management tools or negotiate additional rebates.

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