LEQEMBI (lecanemab-irmb)

Medical Administration – intravenous

Diagnosis considered for coverage:
  • Alzheimer's Disease: Indicated for the treatment of Alzheimer’s disease. Treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with Leqembi. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.

Coverage Criteria:

For diagnosis of Alzheimer’s disease:

  • Dose does not exceed 10 mg/kg every two weeks, AND

  • Prescribed by a neurologist, board-certified geriatrician, or geriatric psychiatrist, AND

  • Both of the following:

    • Based on the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria, one of the following:

      • Diagnosis of mild cognitive impairment due to Alzheimer's disease 

      • Diagnosis of probable Alzheimer's disease dementia, AND 

    • Submission of medical records (e.g., chart notes) confirming all of the following:

      • Global Clinical Dementia Rating (CDR) score of 0.5 or 1.0 

      • CDR Memory Box score of 0.5 or greater 

      • Mini-Mental State Examination score of 22 or greater, AND 

  • Submission of medical records (e.g., chart notes) confirming the presence of beta-amyloid protein deposition, as evidenced by one of the following:

    • Positive amyloid positron emission tomography (PET) scan

    • Both of the following:

      • Attestation that the patient does not have access to amyloid PET scanning 

      • Cerebrospinal fluid (CSF) biomarker testing documents abnormalities suggestive of beta-amyloid accumulation (e.g., Aβ42 level, Aβ42:Aβ40 ratio), AND 

  • Other differential diagnoses (e.g., dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), vascular dementia, pseudodementia due to mood disorder, vitamin B12 deficiency, encephalopathy, etc.) have been ruled out, AND

  • Both of the following:

    • Patient is not currently taking an anticoagulant (e.g., warfarin, dabigatran) 

    • Patient has no history of intracerebral hemorrhage (e.g., transient ischemic attack [TIA], stroke) within the previous year prior to initiating treatment, AND 

  • Counseling has been provided on the risk of amyloid-related imaging abnormalities (ARIA-E and ARIA-H) and patient and/or caregiver are aware to monitor for headache, dizziness, visual disturbances, nausea, and vomiting, AND

  • Submission of medical records (e.g., chart notes) confirming a baseline brain magnetic resonance imaging (MRI) has been completed within 12 months prior to initiating treatment, AND

  • Not used in combination with other Aβ monoclonal antibodies (mAbs) for Alzheimer's Disease (e.g., Aduhelm)

Reauthorization Criteria:

For diagnosis of Alzheimer’s disease:

  • Dose does not exceed 10 mg/kg every two weeks, AND

  • Prescribed by a neurologist, geriatrician, or geriatric psychiatrist, AND

  • Patient is benefitting from therapy as defined by both of the following:

    • Based on the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria, one of the following:

      • Patient continues to have a diagnosis of mild cognitive impairment due to Alzheimer's disease 

      • Patient continues to have a diagnosis of probable Alzheimer's disease dementia, AND 

    • Submission of medical records (e.g., chart notes) confirming all of the following:

      • Global Clinical Dementia Rating (CDR) score of 0.5 or 1.0 

      • CDR Memory Box score of 0.5 or greater 

      • Mini-Mental State Examination score of 22 or greater, AND 

  • Submission of medical records (e.g., chart notes) confirming follow-up brain magnetic resonance imaging (MRI) has been completed prior to the 5th and 7th infusion treatment and after the initiation of therapy to show one of the following:

    • Both of the following:

      • Less than 10 new incident microhemorrhages 

      • 2 or less focal areas of superficial siderosis, AND 

    • If 10 or more new incident microhemorrhages or greater than 2 focal areas of superficial siderosis are present, then both of the following:

      • Patient has been clinically evaluated for ARIA related signs or symptoms (e.g., dizziness, visual disturbances) 

      • Follow-up MRI demonstrates radiographic stabilization (i.e., no increase in size of number of ARIA-H), AND 

  • Not used in combination with other Aβ monoclonal antibodies (mAbs) for Alzheimer's Disease (e.g., Aduhelm)

Coverage Duration: 
  • Initial: 6 months

  • Reauthorization: 6 months

Authorization is not covered for the following:

The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

Additional Information: 
  • Alzheimer disease (AD) refers to beta-amyloid plaques (A) and pathologic tau deposits (T), defined in vivo by abnormal biomarkers of A and T (both are required). In Alzheimer's disease, beta-amyloid levels in CSF are low, and tau and phospho-tau levels are high, compared with levels in people without Alzheimer's or other causes of dementia.

  • Alzheimer’s clinical syndrome is the recommended terminology for clinically ascertained multi- (or single-) domain amnestic syndrome or a classic syndromal variant (i.e., what has historically been labeled “possible or probable AD”). It applies to both mildly impaired and demented individuals. The term “Alzheimer’s disease” is reserved for situations where neuropathologic or biomarker evidence of the disease (i.e. Aβ plaques and pathologic tau deposits) is present.

  • Biomarkers are grouped into those of beta-amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available.

    • PET scans and CSF levels measuring AT(N) biomarkers are evaluated on a continuum. Two common approaches include a single cut point, which labels each biomarker group as normal (−) or abnormal (+), and a two cut point, which labels each biomarker as clearly normal (0), intermediate range (1), or clearly abnormal (2).

  • Mild cognitive impairment (MCI)

    • Cognitive performance below expected range for that individual based on all available information. This may be based on clinical judgment and/ or on cognitive test performance (which may or may not be based on comparison to normative data with or without adjustments for age, education, occupation, sex, etc.).

    • Cognitive performance is usually in the impaired/abnormal range based on population norms, but this is not required as long as the performance is below the range expected for that individual.

    • In addition to evidence of cognitive impairment, evidence of decline in cognitive performance from baseline must also be present. This may be reported by the individual or by an observer (e.g., study partner) or observed by change on longitudinal cognitive testing/behavioral assessments or by a combination of these.

    • MCI may be characterized by cognitive presentations that are not primarily amnestic.

    • Although cognitive impairment is the core clinical criteria, neurobehavioral disturbance (e.g., changes in mood, anxiety, or motivation) may be a prominent feature of the clinical presentation.

    • MCI patients may perform daily life activities independently, but cognitive difficulty may result in detectable but mild functional impact on the more complex activities of daily life as self-reported or corroborated by a study partner.

  • Dementia:

    • Substantial progressive cognitive impairment that affects several domains and/or neurobehavioral symptoms. May be reported by the individual or by an observer (e.g., study partner) or observed by change on longitudinal cognitive testing.

    • Cognitive impairment and/or neurobehavioral symptoms result in clearly evident functional impact on daily life. No longer fully independent/requires assistance with daily life activities. This is the primary feature differentiating dementia from MCI.

    • May be subdivided into mild, moderate, and severe.

  • Clinical Dementia Rating-Global (CDR-G) score is useful for characterizing and tracking a patient's level of impairment/dementia:

    • 0 = normal

    • 0.5 = very mild dementia

    • 1 = mild dementia

    • 2 = moderate dementia

    • 3 = severe dementia.

  • Clinical Dementia Rating Sum of Boxes (CDR-SB) assessment is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias: Memory, Orientation, Judgment & Problem Solving, Community Affairs, Home & Hobbies, and Personal Care. The information is obtained through an interview of the patient and a reliable informant (e.g., family member). This score is useful for characterizing and tracking a patient's level of impairment/dementia.

    • 0 suggests normal

    • 0.5 to 4 suggests questionable cognitive impairment

    • 0.5 to 2.5 suggests questionable impairment

    • 3.0 to 4.0 suggests very mild dementia

    • 4.5 to 9.0 suggests mild dementia

    • 9.5 to 15.5 suggests moderate dementia

    • 16.0 to 18.0 suggests severe dementia

  • Mini-Mental State Examination (MMSE) is a series of questions asked by a health professional designed to test a range of everyday mental skills. The maximum score is 30 points where the following levels of dementia are indicated and a score of:

    • 25 to 30 suggest normal cognition

    • 20 to 24 suggests mild dementia,

    • 13 to 20 suggests moderate dementia,

    • less than 12 indicates severe dementia.

    • On average, the MMSE score of a person with Alzheimer's declines about two to four points each year.

  • ARIA-E refers to the magnetic resonance (MR) signal alterations thought to represent vasogenic edema (VE) and related extravasated fluid phenomena.

  • ARIA-H refers to the MR signal alterations on attributable to microhemorrhages (mH) and hemosiderosis. The manufacturer recommends obtaining MRIs prior to the 7th and 12th infusions. If radiographic severe ARIA-H is observed, treatment may be continued with caution only after a clinical evaluation and a follow-up MRI demonstrates radiographic stabilization (i.e., no increase in size or number of ARIA-H).

  • Superficial siderosis (SS) is a rare condition in which hemosiderin is deposited on the pial surface of the brain and/or spinal cord. Hemosiderin deposition is the consequence of recurrent or persistent hemorrhage in the subarachnoid space.

Policy Updates:
  • 05/16/2023  – New policy approved by P&T.

References:
  • Leqembi Prescribing Information. Eisai, Inc. Nutley, NJ. January 2023. 

  • McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263-269. 

  • Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):270-279. 

  • A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease (Clarity AD): https://www.clinicaltrials.gov/ct2/show/NCT03887455. Accessed January 6, 2023. 

  • A study to Evaluate Safety, Tolerability, and Efficacy of Lecanemab in Subjects with Early Alzheimer’s Disease. https://www.clinicaltrials.gov/ct2/show/NCT01767311. Accessed January 6, 2023. 

Last review date: June 1, 2023