Background

Alzheimer’s disease (AD) is a neurodegenerative disorder of uncertain cause and pathogenesis that is the most common cause of dementia. The hallmark neuropathologic changes of AD are diffuse and neuritic plaques, marked by extracellular amyloid beta deposition, and neurofibrillary tangles, comprised of the intracellular accumulation of hyperphosphorylated tau protein. The most essential and earliest clinical manifestation of AD is selective memory impairment, although there are exceptions. While treatments are available that can ameliorate some symptoms of the illness, there is no cure currently available, and the disease inevitably progresses in all patients.

Leqembi is an amyloid beta-directed antibody indicated for the treatment of Alzheimer’s disease.

Lecanemab-irmb (Leqembi™) is a recombinant human immunoglobulin gamma 1 (IgG1) monoclonal antibody, directed against aggregated soluble and insoluble forms of amyloid beta. The accelerated approval of lecanemab-irmb (Leqembi) is based on a surrogate endpoint of reduction in brain amyloid plaques, which is a biomarker with little evidence that proves an association with clinical benefit, such as improvement in cognition. Continued approval of this agent by the FDA is contingent upon demonstrating clinical benefit in confirmatory trials.

Policy

Leqembi may be considered MEDICALLY NECESSARY when all of the following criteria has been met:

• Patient must be ≥ 50 years/old
• Prescribed by or in cooperation with a Neurologist, Gerontologist, or Neuropsychiatrist.
• Confirmed diagnosis of Mild Cognitive Impairment or Mild Dementia associated with Alzheimer’s as defined by any (two) of the following tests:
  • Mini Mental Status Exam (MMSE) of 21-30
  • Functional Assessment Staging Test (FAST) 2-4
  • Montreal Cognitive Assessment (MoCA) ≥ 16
  • Clinical Dementia Rating -Global scale (CDR-GS) of 0.5-1
• Must not have any other diagnosis that could contribute to cognitive impairment, (ie vascular dementia, traumatic brain injury, substance abuse, etc.)
• Patient must have an MRI within 12 months prior to initiating treatment to evaluate for pre-existing Amyloid Related Imaging Abnormalities (ARIA)
• A positive Amyloid PET imaging and/or cerebrospinal fluid (CSF) analysis consistent with Alzheimer’s disease or results from a lumbar puncture confirming the presence of elevated phosphorylated tau (P-tau) protein and/or elevated total tau (T-tau) protein, and reduced beta amyloid-42 (AB42) OR a low AB42/AB40 ratio as determined by the lab assay detected in cerebrospinal fluid (CSF).
• Confirmed ApoE e4 genetic testing prior to initial approval.
• Patient must not be a Homozygous carrier of ApoE e4.
• Do not have a history of Transient Ischemic Attack (TIA), stroke, or seizure in the past 12 months, advanced chronic heart failure, myocardial infarction or any severe cardiovascular or bleeding disorder.
• Must not be on current anticoagulant therapy other than aspirin treatment (no greater than 325 mg/day.)
• Patient must not be treated concurrently with any other anti-amyloid therapy [Aducanumab-awwa]

Initial duration 3 months

Reauthorization Criteria

Continuation of Leqembi may be considered MEDICALLY NECESSARY when all of the following criteria has been met: 

• Member meets original authorization criteria.
• Member has been evaluated for evidence of amyloid-related imaging abnormalities (ARIA) on MRI prior to the 5th dose (first reauthorization), 7th dose, and 14th dose (second reauthorization). Ongoing evaluation for ARIA clinical and/or radiographical for any subsequent reauthorization.  
• For members with radiographic evidence of amyloid related imaging abnormalities (ARIA):    
  • Dosing may continue based on clinical judgement, if applicable, for members that meet the following criteria:
    • • Member has mild ARIA on MRI and is asymptomatic or has mild clinical symptoms.
  • For all other symptoms of ARIA, dosing should be suspended until MRI demonstrates radiographic resolution and symptoms have resolved.
• Member has not progressed to Moderate to Severe Cognitive Impairment or Moderate to Severe Alzheimer’s dementia as demonstrated on any of the following tests:
  • MMSE ≤ 21 or CDR-GS ≤ 1 or MoCA ≤ 16
• Member has not developed or had any new serious cardiovascular events or disorders.

References

1. Leqembi™ (lecanemab-irmb), injection for intravenous use [package insert]. Eisai, Inc. Nutley, NJ. Revised 07/2023.
2. Van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early alzheimer’s disease. NEJM. 2023; 388(1):9-21.
3. Swanson CJ, Zhang Y, Dhadda S, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early alzeihmer’s disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimer’s Research & Therapy. 2021; 13:80-94.
4. Clinical Pharmacology Compendium. 2023. Tampa FL: Gold Standard, Inc. Lecanemab-irmb.
5. Micromedex DrugDex Compendium®. 2023. Lecanemab-irmb.
6. Epidemiology, pathology, and pathogenesis of Alzheimer disease. UpToDate. Last updated August 2022. www.uptodate.com (http://www.uptodate.com/). Last accessed April 2023.
7. Leqembi prescribing information. Eisai R&D Management Co. Ltd. January 2023. Last accessed April 2023.
8. Treatment of Alzheimer disease. UpToDate. Last updated September 2021. www.uptodate.com (http://www.uptodate.com/). Last accessed April 2023.

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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