CMS is announcing a final Medicare national coverage determination (NCD) that covers Food and Drug Administration (FDA) approved monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease (AD) when furnished in accordance to the Coverage Criteria specified below under coverage with evidence development (CED) for patients who have a clinical diagnosis of mild cognitive impairment (MCI) due to AD or mild AD dementia, both with confirmed presence of amyloid beta pathology consistent with AD.
Coverage Criteria:
1) Monoclonal antibodies directed against amyloid that are approved by FDA for the treatment of AD based upon evidence of efficacy from a change in a surrogate endpoint (e.g., amyloid reduction) considered as reasonably likely to predict clinical benefit may be covered in a randomized controlled trial conducted under an investigational new drug application (IND).
2) Monoclonal antibodies directed against amyloid that are approved by FDA for the treatment of AD based upon evidence of efficacy from a direct measure of clinical benefit may be covered in CMS-approved prospective comparative studies. Study data for CMS-approved prospective comparative studies may be collected in a registry.
3) For CMS-approved studies, the protocol, including the analysis plan, must include:
a. A study population whose diversity of patients are representative of the national population with MCI due to AD or mild AD dementia.
b. A neurocognitive evaluation and instruments used to assess cognition and function for the clinical diagnosis of MCI due to AD or mild AD dementia for study enrollment and outcomes assessment.
c. A description of:
i. The multidisciplinary dementia team and optimal medical management.
ii. Study sites with clinical expertise and infrastructure to provide treatments consistent with the safety monitoring outlined in the FDA-approved label.
4) CMS-approved studies of antiamyloid mAbs approved by FDA for the treatment of AD based upon evidence of efficacy from a direct measure of clinical benefit must address all of the questions below:
a) Does the antiamyloid mAb meaningfully improve health outcomes (i.e., slowing in the decline of cognition and function) in broad community practice?
b) Do benefits and harms such as brain hemorrhage and edema, associated with use of the antiamyloid mAb, depend on characteristics of patients, treating clinicians, and settings?
c) How do the benefits and harms change over time?
By publishing this CMS coverage criteria, we are creating a predictable pathway to Medicare coverage for any antiamyloid mAb that meets the finalized coverage criteria. Under the final NCD, CMS has ensured access to antiamyloid mAbs that have similar functions and medical uses when FDA approves those drugs using the traditional approval process and the patient meets the coverage criteria outlined in the NCD.
The final decision allows for flexibility in a less rigorous study design for antiamyloid mAbs that have been approved by FDA through the traditional approval process for the treatment of AD based upon evidence of efficacy from a direct measure of clinical benefit. For antiamyloid mAbs that have demonstrated a meaningful clinical benefit through the FDA traditional approval process, that antiamyloid mAb is eligible to be used on label, for FDA-approved indications, in clinical studies or other prospective comparative studies to answer the CED questions specified in the NCD. While the degree of rigor in the CED study design for a particular antiamyloid mAb will be determined in large part by the strength of evidence in the initial, successful trial(s) that lead to FDA approval of that particular drug, one example is of a study is data generated through routine clinical practice or a registry. Registry data may then be used to assess whether outcomes seen in carefully controlled clinical trials are reproduced in real-world use and in a broader range of patient groups.
Questions & Answers:
Q. Why has CMS expanded coverage beyond the CMS-approved RCTs that were described in the proposed decision?
A. The final decision allows for flexibility in a less rigorous study design for antiamyloid mAbs that have been approved by FDA through the traditional approval process for the treatment of AD. For antiamyloid mAbs that have been approved through the FDA traditional approval process, that antiamyloid mAb is eligible for coverage under prospective comparative studies to answer the CED questions specified in the NCD. Prospective comparative studies may include a variety of study designs ranging from longitudinal comparative studies to pragmatic clinical trials, and all study data may be collected in a registry. The degree of rigor in the CED study design for a particular antiamyloid mAb will be determined in large part by the strength of evidence in the initial, successful trial(s) that lead to FDA approval of that particular drug.
While the degree of rigor in the CED study design for a particular antiamyloid mAb will be determined in large part by the strength of evidence in the initial, successful trial(s) that lead to FDA approval of that particular drug, one example of a study is data generated through routine clinical practice or a registry. Registry data may then be used to assess whether outcomes seen in carefully controlled clinical trials are reproduced in real-world use and in a broader range of patient groups.
Q. Why did CMS remove the exclusion criteria specified in the proposed decision?
A. The proposed NCD included criteria that would have excluded some key patient subpopulations (e.g., Down syndrome patients). Based on public comment, we are not finalizing the patient exclusion criteria to allow appropriate access to patient subpopulations that may need treatment based on ongoing research. We believe this is sufficiently addressed in the CED criteria and protocol review and believe these criteria are no longer needed in the NCD language.
Q. Are patients with Down syndrome or other subpopulations eligible for coverage under this final NCD?
A. There may be subpopulations that are important to study such as individuals with Down syndrome. CMS supports NIH and other federal agency trials in a broad range of clinical topics, which may include patients with Down syndrome (see Medicare clinical trial policy, Section 310.1 of the NCD manual or https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?ncdid=1&ncdver=2&chapter=all&sortBy=title&bc=18).
Q. Why did CMS remove the restriction specified in the proposed decision that all trials must be conducted in a hospital-based outpatient center?
A. In the proposed decision, we expressed that approved clinical trials should remain in hospital-based outpatient facilities to ensure integrated and coordinated care, availability of advanced imaging or other diagnostic tests, and rapidly-available advanced care if needed. These continue to be important factors for optimized patient health outcomes. Based on public comment, we do not restrict the setting in this final decision to ensure that antiamyloid mAbs that have received FDA approval based upon evidence of efficacy from a direct measure of clinical benefit may be given to a broader patient population. This is important to answer the first CED question regarding Medicare patient outcomes in broader community settings. To ensure there continues to be integrated and coordinated advanced care, if needed, CMS is requiring 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. This protocol requirement will help to ensure appropriate clinical care, and reassure patients and their caregivers that further research with antiamyloid mAbs will be conducted in settings to minimize potential harms from the treatment.
Q. Will this NCD inhibit innovation and the development of therapies to combat Alzheimer’s disease?
A. No, this decision facilitates innovation by defining the criteria by which a forthcoming therapy for Alzheimer’s disease could be covered by Medicare. The CMS final decision provides clarity on the criteria to receive coverage for any drug in this class (and thus what evidence is necessary to meet the standard for “reasonable and necessary” for this particular treatment). Medical innovation must include evidence that demonstrate health outcomes to patients in consideration with potential harms.
Q. Are Medicare Part D plans covering this drug?
A. Generally, when payment for an FDA-approved drug as prescribed and dispensed or administered is not available for a beneficiary under Parts A or B, the drug would meet the statutory definition of a Part D drug and can be covered by the beneficiary’s Part D sponsor. For purposes of this NCD, when Aduhelm or other drugs included in the NCD are non-covered by Medicare Part B under the terms of the NCD, CMS considers them Part D drugs. However, a Part D sponsor (including the sponsor of an MA-PD plan) may exclude from Part D coverage any drug for which payment under Part A and Part B would not be made because such drug is not reasonable and necessary.
Q. What are Medicaid’s obligations to cover this drug for full-benefit dually eligible beneficiaries when it is not covered under the NCD – that is, when a full-benefit dually eligible individual is not part of a randomized clinical trial?
A. For purposes of this NCD, when Aduhelm or other drugs included in the NCD are non-covered by Medicare Part B under the terms of the NCD, CMS considers them Part D drugs. Medicaid does not pay for Part D drugs for full-benefit dually eligible individuals, regardless of whether they are enrolled in a Part D plan. This means that when the drugs included in the NCD are non-covered by Part B under the terms of the NCD, regardless of whether a full-benefit dually eligible individual’s Part D plan actually covers the drug, Medicaid will not cover them.
Q: Is Medicaid required to cover this drug for Medicaid-only individuals?
A. Generally, states are required to cover the drug if the manufacturer has in effect a National Drug Rebate Agreement with HHS and when the drug is used for a medically accepted indication, subject to any permissible restrictions or limitations on coverage applied by the state (e.g., prior authorization). Because the manufacturer of Aduhelm has entered into and has in effect a Medicaid drug rebate agreement and because Aduhelm also satisfies the definition of a covered outpatient drug, as set forth at section 1927(k)(2) of the Social Security Act (Act), state Medicaid programs are required to cover the drug when used for a medically accepted indication. However, state Medicaid programs could subject Aduhelm to utilization management techniques, such as prior authorization, and medical necessity criteria. As a covered outpatient drug, states may invoice the manufacturer for rebates on the drug, and manufacturers would be required to pay rebates, as appropriate, when dispensed and paid for under the state plan.
To read the final NCD CED decision memorandum, visit https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&ncaid=305.
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