CMS Updates Monoclonal Antibody Coverage for Alzheimer's Disease Under NCD 375

CMS has modified its national coverage determination for monoclonal antibodies directed against amyloid for the treatment of Alzheimer's disease, effective March 12, 2026. This update to NCD 375 affects how Medicare covers antiamyloid monoclonal antibodies (antiamyloid mAbs) — including agents like lecanemab and donanemab — and maintains a coverage with evidence development (CED) framework that carries significant documentation and enrollment obligations for participating providers.

What CMS Covers Under NCD 375: The CED Framework Explained

The Centers for Medicare & Medicaid Services covers FDA-approved antiamyloid mAbs for the treatment of Alzheimer's disease — but coverage is not unconditional. It is tied to coverage with evidence development (CED), meaning Medicare will pay only when the drug is furnished as part of an approved clinical study or registry.

This approach was first established effective April 7, 2022, and the 2026 modification continues and refines that framework. For billing teams, this distinction is critical: a patient receiving an antiamyloid mAb in a standard outpatient infusion setting — without enrollment in a qualifying CMS-approved study — does not meet coverage criteria under this NCD.

Coverage applies specifically to patients who meet all of the following clinical criteria:

• Clinical diagnosis of mild cognitive impairment (MCI) due to AD or mild AD dementia
• Confirmed presence of amyloid beta pathology consistent with Alzheimer's disease

These aren't soft requirements. Amyloid confirmation — typically via PET imaging or cerebrospinal fluid biomarker testing — must be documented before coverage is established. If that confirmation isn't in the record, the claim is at risk.

Two Coverage Pathways Under NCD 375: Know Which One Applies

NCD 375 establishes two distinct coverage tiers based on the FDA approval pathway for the specific drug being administered.

Pathway 1 — Accelerated Approval (Surrogate Endpoint): Antiamyloid mAbs approved by the FDA based on a surrogate endpoint — such as amyloid reduction — may be covered when administered as part of a randomized controlled trial conducted under an investigational new drug (IND) application.

Pathway 2 — Traditional Approval (Clinical Benefit Endpoint): Antiamyloid mAbs approved by the FDA based on a direct measure of clinical benefit (i.e., demonstrated slowing of cognitive decline) may be covered in CMS-approved prospective comparative studies. Study data for these can be collected through a registry.

The clinical and administrative obligations differ between the two pathways. Pathway 2 studies must specifically address three outcomes questions:

1. Does the drug meaningfully improve health outcomes — specifically, slowing cognitive and functional decline — in broad community practice?
2. Do benefits and harms (including brain hemorrhage and edema, i.e., ARIA — amyloid-related imaging abnormalities) vary based on patient characteristics, treating clinicians, or care settings?
3. How do benefits and harms evolve over time?

For billing managers: the drug your facility is administering determines which pathway — and which study enrollment requirement — governs coverage. Mixing these up is a fast route to a denial.

CMS Study Integrity and Protocol Requirements That Affect Billing

CMS-approved studies under NCD 375 must meet specific protocol standards. These aren't just clinical requirements — they have downstream billing implications, because failing to meet them can invalidate the coverage basis for claims already submitted.

Required study protocol elements include:

• A study population representative of the national population with MCI due to AD or mild AD dementia, including demographic diversity
• A documented neurocognitive evaluation with described instruments used to assess cognition and function — both at enrollment and for outcomes assessment
• A description of the multidisciplinary dementia team and the optimal medical management plan
• Evidence that study sites have the clinical expertise and infrastructure to provide treatment consistent with FDA-approved safety monitoring requirements (this includes MRI monitoring for ARIA)

The AHRQ standards of scientific integrity also apply: the principal purpose of the study must be to test whether the treatment meaningfully improves health outcomes for enrolled subjects. Studies designed primarily around commercial access — rather than genuine evidence generation — don't qualify.

Affected Codes

This policy does not list specific CPT, HCPCS, or ICD-10 codes in the policy data available for this update. Historically, billing for antiamyloid mAb infusions has involved HCPCS J-codes specific to each FDA-approved agent (assigned by CMS after approval), along with infusion administration codes. Because NCD 375 does not enumerate codes in this version, billing teams should:

• Reference the applicable HCPCS J-code for the specific antiamyloid mAb being administered (confirm current assignment in the CMS HCPCS quarterly updates)
• Use the appropriate infusion administration CPT code based on duration and setting
• Append the CED-specific condition code or modifier required for claims tied to coverage with evidence development — confirm current requirements with your MAC

Contact your Medicare Administrative Contractor (MAC) directly for current coding guidance specific to the study or registry your facility is enrolled in.

What Your Billing Team Should Do