LECANEMAB-IRMB INJ,SOLN
Clinical Criteria Summary
Document 408: Lecanemab irmb LEQEMBI CFU
Exclusion Criteria
- Any medical, neurological, or mental health condition that may be a contributing/primary cause of cognitive impairment
- Age less than 60 years
- Contraindication to or unable to complete brain MRI
- Transient ischemic attack, stroke, or seizures within the past year
- Evidence of other clinically significant lesions on brain MRI that indicate another cause of dementia
- Evidence on screening MRI that would exclude treatment (including: more than 4 microhemorrhages; a single macro hemorrhage greater than 10 mm at greatest diameter; an area of superficial siderosis; evidence of vasogenic edema; evidence of acute/subacute cerebral contusion, acute/subacute stroke, aneurysms, vascular malformations, or infective lesions; severe small vessel, or white matter disease; space occupying lesions; or intra-axial brain tumors)
- ApoE e4 homozygote
- Any immunological disease which is not controlled, or which requires treatment with biologic drugs
- Untreated bleeding disorder, platelet count <50,000 x 109/L, or international normalized ratio [INR] >1.5
- Thyroid stimulating hormone above normal range (TSH > 5 mU/L if < 65 years old; TSH > 7.5 mU/L if > 65 years old)
- Low serum vitamin B12 level
- Untreated human immunodeficiency virus (HIV)
- Malignant neoplasm under active therapy (unless approved by oncologist)
- Answer “yes” to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation item 4 or 5, or any suicidal behavior assessment within the past 6 months
- Hospitalized or treated for suicidal behavior in the past 5 years
- Current substance use disorder or positive urine drug screen
- Receiving medication(s) with anti-platelet or anti-coagulant properties (e.g., apixaban, clopidogrel, NSAIDs, t-PA), except aspirin
Inclusion Criteria
- Prescriber is a VA (not VA Community care) board certified neurologist, geriatric psychiatrist, or geriatrician who specializes in treating dementia
- Patient has a signed informed consent on file; if genotype testing is not performed, the patient and provider accept the risk
- Patient meets criteria for mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD) dementia
- Patient has had an MRI scan within the last 6 months
- Amyloid PET imaging, cerebrospinal fluid (CSF) analysis consistent with AD (e.g., Beta-amyloid (1-42) [Abeta42] < 1030 pg/ml, or a clearly positive blood biomarker (e.g., FDA-cleared Lumipulse G pTau 217/B-Amyloid 42 Plasma Ratio >0.00738)
- Mini-Mental State Examination (MMSE) score > 21, or Saint Louis University Mental Status (SLUMS) score or Montreal Cognitive Assessment (MoCA) score of > 16, or Functional Assessment Staging Test (FAST) Stage score of 2-4
- Neuroradiology is available to review serial MRI scans, either at site, or through National Teleradiology
- A process is in place before starting therapy to ensure the provider and pharmacy are notified to hold the infusion until the ordering physician can assess the patient and decide whether to continue treatment
Additional Inclusion Criteria
- If the request is for once weekly 360 mg subcutaneous administration, the patient has received at least 18 months of the intravenous starting dose
Program & Safety Requirements
- Facilities and providers need to enroll in the VA MedSAFE real-time medication use evaluation (MUE) for this medication
Document 409: MON Lecanemab irmb LEQEMBI monograph
Indication & Disease State
- • Treatment of Alzheimer’s disease
- • Initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease
- • Confirmed presence of Aβ pathology
Patient Selection & Inclusion Criteria
- • Diagnosis of MCI due to AD (CDR score 0.5) or mild AD (CDR score 0.5-1)
- • Memory impairment [Wechsler Memory Scale IV-Logical Memory (subscale) II] >1 standard deviation below age-adjusted mean
- • Positive biomarker for brain amyloid pathology (PET, CSF t-tau/Aβ)
- • Aged > 50 and < 90 years
- • MMSE score between 22 and 30
- • BMI > 17 and < 35
- • If using drugs to treat symptoms related to AD, doses must be stable for at least 12 weeks prior to baseline
Exclusion Criteria
- • Any neurological condition (other than AD) that may contribute to cognitive impairment
- • Transient ischemic attack, stroke, or seizures within 1 year prior to screening
- • Psychiatric diagnosis or symptoms interfering with procedures (e.g., hallucinations, major depression, delusions)
- • Geriatric Depression Scale (GDS) score ≥ 8 at screening
- • Contraindications to MRI scanning (cardiac pacemaker/defibrillator, ferromagnetic metal implants)
- • Evidence of other clinically significant lesions on brain MRI indicating a dementia diagnosis other than AD
- • Significant pathological findings on brain MRI: >4 microhemorrhages; single macro hemorrhage >10 mm; superficial siderosis; vasogenic edema; cerebral contusion, encephalomalacia, aneurysms, vascular malformations, infective lesions; multiple lacunar infarcts/stroke involving a major vascular territory, severe small vessel/white matter disease; space-occupying lesions; brain tumors
- • Immunological disease not adequately controlled or requiring biologic drugs during treatment
- • Bleeding disorder not under adequate control (platelet count <50,000 or INR >1.5)
- • Thyroid stimulating hormone above normal range
- • Abnormally low serum vitamin B12 levels
- • HIV positive status
- • Malignant neoplasms within 3 years of screening
- • Suicidal ideation Type 4 or 5 on C-SSRS, suicidal behavior within 6 months before/at screening/baseline, or hospitalization/treatment for suicidal behavior in past 5 years
- • Drug or alcohol abuse/dependence within 2 years before screening or positive urine drug test at screening
Dosing & Administration
- • Injection: 100 mg/ml
- • Intravenous (IV) infusion, 10 mg/kg, over an hour, every 2 weeks
Monitoring & Safety Management
- • Requires a recent (within one year) brain MRI prior to initiating treatment
- • Periodic MRI monitoring required prior to the 5th, 7th, and 14th infusions
- • Enhanced clinical vigilance for amyloid-related imaging abnormalities (ARIA) during the first 14 weeks of treatment
- • Mild ARIA: Continue dosing if asymptomatic; suspend dosing if symptomatic
- • Moderate to severe ARIA: Temporarily suspend dosing until resolution
- • Severe ARIA-H: Permanently discontinue dosing
- • Infusion-related reactions: Reduce or discontinue infusion rate and administer appropriate therapy as clinically indicated; consider pre-medication with antihistamine, NSAIDs, or corticosteroids at subsequent dosing