Is Leqembi (lecanemab-irmb) medically indicated for a patient with Alzheimer's disease (G30.0)?

Medical Necessity Review: Lecanemab (Leqembi) for Early-Onset Alzheimer's Disease

Based on the submitted documentation, this claim cannot be approved as medically necessary due to insufficient clinical information to verify compliance with multiple critical eligibility criteria required by both FDA labeling and the insurance plan's clinical policy.

Critical Documentation Deficiencies

The case summary reveals insufficient information to determine if the patient meets the following essential criteria:

Exclusion Criteria Assessment (Section I)

• Neuroimaging requirements not met: No documentation of recent brain MRI to exclude cerebral microbleeds (>4), cortical superficial siderosis, vascular malformations, or other contraindications 1
• Vascular and bleeding history unclear: No documentation regarding history of TIA, stroke, uncontrolled hypertension, or seizures within past 12 months 1
• Coagulation status undocumented: No platelet count or INR values provided to exclude bleeding disorders 1

Disease Stage and Cognitive Assessment (Sections III.B-D)

• Clinical staging not documented: No evidence provided confirming Clinical Stage 3 or 4 AD per required criteria 1
• Baseline cognitive assessment missing: No CDR-GS, MMSE, or MoCA scores documented at baseline 1
• Objective cognitive impairment not established: No formal neuropsychological testing results provided 1

Amyloid Pathology Confirmation (Section III.E)

• Amyloid biomarker confirmation absent: No PET scan results or CSF biomarker analysis (Aβ42/Aβ40 ratio, P-tau/Aβ42 ratio, or T-tau/Aβ42 ratio) documented 1, 2
• FDA requirement not met: Lecanemab prescribing information explicitly requires confirmation of amyloid beta pathology prior to initiating treatment 1

Safety Monitoring Requirements (Sections III.F, I)

• Baseline MRI not documented: FDA labeling mandates recent baseline brain MRI within one year prior to treatment initiation to evaluate for pre-existing ARIA 1
• APOE ε4 genotype testing not documented: Required to inform patient of ARIA risk, particularly critical given that APOE ε4 homozygotes have 34.5% incidence of ARIA-E versus 13.6% overall 1, 3

Registry Participation (Section III.J)

• Registry enrollment not confirmed: No documentation of provider enrollment in required patient registry (e.g., ALZ-NET) 1

Clinical Context and Safety Concerns

ARIA Risk Profile

Lecanemab carries an FDA boxed warning for amyloid-related imaging abnormalities, which can be fatal 1. The safety profile from the Clarity AD trial demonstrates:

• ARIA-E incidence: 13.6% overall, but 34.5% in APOE ε4 homozygotes 3
• ARIA-H microhemorrhages: 16.0% incidence 3
• Fatal outcomes reported: 3 deaths due to intracerebral hemorrhage in Core + OLE studies, including patients on concurrent anticoagulation 3

Without documented APOE ε4 status and baseline MRI, the risk-benefit assessment cannot be properly conducted 1.

Appropriate Patient Selection

The FDA indication specifies treatment should be initiated in patients with mild cognitive impairment or mild dementia stage of disease 1. The diagnosis code G30.0 (early-onset Alzheimer's disease) alone does not establish:

• Current disease stage (MCI vs. mild dementia vs. moderate/severe dementia)
• Presence of amyloid pathology (required for treatment initiation) 1
• Absence of exclusionary conditions 1

Required Documentation for Approval

To establish medical necessity, the following must be submitted:

1. Amyloid pathology confirmation: Amyloid PET scan report OR CSF biomarker analysis showing low Aβ42/Aβ40 ratio, elevated P-tau/Aβ42 ratio, or elevated T-tau/Aβ42 ratio 1, 2

2. Disease staging documentation: Clinical assessment confirming Clinical Stage 3 or 4 AD with baseline cognitive scores (CDR-GS of 0.5-1, MMSE 21-30, or MoCA ≥16) 1

3. Safety screening: Recent brain MRI (within 1 year) report documenting absence of exclusionary findings, complete blood count with platelet count, INR/PT, and medical history addressing TIA/stroke/seizure/hypertension history 1

4. APOE ε4 genotype testing: Results required for informed consent discussion regarding ARIA risk 1

5. Registry enrollment confirmation: Documentation of provider participation in approved patient registry 1

Recommendation

Deny as submitted with request for additional clinical documentation. The prescriber should be contacted to provide the missing information outlined above. Once complete documentation is received demonstrating the patient meets all eligibility criteria and has no exclusionary conditions, the claim can be reconsidered for approval 1.

The fact that the patient has already received an infusion does not establish medical necessity retrospectively—proper documentation of eligibility criteria must be verified before coverage can be authorized 1.