Monoclonal Antibodies Directed Against Amyloid for the Treatment of Alzheimer's Disease (AD) — NCD 375 | CMS Coverage Update

TL;DR: The Centers for Medicare & Medicaid Services modified NCD 375 governing monoclonal antibodies directed against amyloid for Alzheimer's disease treatment, with an effective date of January 9, 2026. Here's what billing teams need to know before claims go out the door.

CMS antiamyloid monoclonal antibody coverage policy has been one of the most scrutinized in Medicare billing since its original April 7, 2022 effective date. NCD 375 Medicare coverage remains tied to a coverage with evidence development (CED) framework — meaning your patients don't just need a diagnosis, they need to be enrolled in qualifying studies. This policy does not list specific CPT or HCPCS codes in the current data, which creates a real documentation burden that your billing team needs to address now.

Quick-Reference Table

CMS Antiamyloid Monoclonal Antibody Coverage Criteria and Medical Necessity Requirements 2026

The core structure of this coverage policy has not changed in spirit — but the details matter enormously for medical necessity documentation. CMS covers FDA-approved monoclonal antibodies directed against amyloid for Alzheimer's disease only under coverage with evidence development (CED). That means standard fee-for-service billing without a qualifying study enrollment is not sufficient.

Two distinct coverage tracks exist under NCD 375, and they carry different requirements. Track one covers drugs approved by the FDA based on a surrogate endpoint — like amyloid reduction — in a randomized controlled trial conducted under an investigational new drug (IND) application. Track two covers drugs approved based on direct clinical benefit evidence, through CMS-approved prospective comparative studies.

The distinction between these two tracks is not academic. It directly determines what type of study your patient must be enrolled in to generate a covered claim. If your infusion center is billing for lecanemab (Leqembi) or donanemab (Kisunla), you need to know which FDA approval pathway each drug followed and which track applies.

Medical necessity under this coverage policy requires a clinical diagnosis of mild cognitive impairment (MCI) due to AD or mild Alzheimer's disease dementia. That alone is not enough. The patient must also have confirmed amyloid beta pathology consistent with AD. That confirmation — typically via PET scan or cerebrospinal fluid analysis — must be documented in the medical record before your claim goes out.

The prior authorization question gets complicated here because the real "authorization" under CED is study enrollment. Your billing team should treat study enrollment documentation the same way you'd treat a prior authorization letter. If it's not in the chart, the claim is at risk.

Reimbursement for these drugs runs through Medicare Part B as administered biologicals. That places them in a different billing workflow than oral specialty drugs under Part D. Make sure your charge capture reflects the infusion setting, the drug itself, and the administration codes — even though NCD 375 does not specify codes directly.

CMS Antiamyloid mAb Exclusions and Non-Covered Indications

Coverage under NCD 375 is narrow by design. CMS does not cover antiamyloid monoclonal antibodies outside the CED framework, period. If a patient doesn't meet the study enrollment criteria, the claim will deny.

The patient population is also specifically limited. Moderate or severe Alzheimer's disease dementia is not covered under this policy. The clinical criteria explicitly require mild cognitive impairment (MCI) due to AD or mild AD dementia — not moderate, not severe. Billing for patients who have progressed beyond the mild stage without updated clinical documentation confirming they still qualify at the time of treatment is a claim denial waiting to happen.

Drugs approved only on surrogate endpoint evidence are restricted to randomized controlled trials under IND. They cannot be billed under the track two prospective comparative study pathway. Mixing up which track applies to which drug is one of the most common documentation errors in antiamyloid mAb billing.

Coverage Indications at a Glance

CMS Antiamyloid Monoclonal Antibody Billing Guidelines and Action Items 2026

This is where the policy gets practical. The CED structure creates specific workflow requirements that sit upstream of your billing team but directly affect your claim outcomes.

CPT, HCPCS, and ICD-10 Codes for Antiamyloid Monoclonal Antibodies Under NCD 375

Covered CPT and HCPCS Codes

NCD 375 does not list specific CPT or HCPCS codes in the current policy data. This is a meaningful gap for antiamyloid mAb billing.

In practice, your billing team will need to identify the correct HCPCS J-codes for each specific drug administered. HCPCS codes for biologicals administered in the outpatient setting are assigned at the drug level — not the indication level. The absence of codes in the NCD itself means your local Medicare Administrative Contractor (MAC) guidance and the drug's FDA-approved labeling become your primary references for code selection.

Do not guess at J-codes. Pull the current CMS HCPCS file for lecanemab and donanemab specifically, and confirm with your MAC that the codes you're using are accepted under this NCD. A claim denial based on wrong code selection for an expensive biologic is a cash flow problem your practice can't afford.

Key ICD-10-CM Diagnosis Codes

The policy data does not list specific ICD-10-CM codes. Based on the covered population criteria in the policy, your coding team should be working with codes that reflect MCI due to Alzheimer's disease and mild Alzheimer's disease dementia. Confirm the specific codes with your coding supervisor and ensure they match the severity staging documented by the treating clinician.