DONANEMAB-AZBT INJ,SOLN
Clinical Criteria Summary
Document 631: Donanemab azbt KISUNLA CFU
Patient Demographics & Diagnosis
- Age less than 60 years (Exclusion)
- Meets criteria for mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD) (Inclusion)
Neurological & Cognitive Status
- Any medical, neurological, or mental health condition that may be a major contributing or primary cause of cognitive impairment (Exclusion)
- Transient ischemic attack, stroke, or seizures within the past year (Exclusion)
- Evidence of other clinically significant lesions on brain MRI that indicate another cause of dementia (Exclusion)
- 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 (Inclusion)
Imaging & Biomarker Requirements
- Contraindication to or unable to complete brain MRI (Exclusion)
- Evidence on screening MRI that would exclude treatment: 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 (Exclusion)
- Brain MRI scan within the last 6 months (Inclusion)
- 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)) (Inclusion)
- Neuroradiology is available to review serial MRI scans, either at site, or through National Teleradiology (Inclusion)
Laboratory & Hematologic Parameters
- Untreated bleeding disorder, platelet count <50,000 x 109/L, or international normalized ratio [INR] >1.5 (Exclusion)
- Thyroid stimulating hormone above normal range (TSH > 5 mU/L if < 65 years old; TSH > 7.5 mU/L if >65 years old) (Exclusion)
- Low serum vitamin B12 levels (Exclusion)
Comorbidities & Medication Restrictions
- ApoE e4 homozygote (Exclusion)
- Any immunological disease which is not controlled, or which requires treatment with biologic drugs (Exclusion)
- Untreated human immunodeficiency virus (HIV) (Exclusion)
- Malignant neoplasm under active therapy (unless approved by oncologist) (Exclusion)
- Receiving medication(s) with anti-platelet or anti-coagulant properties (e.g., apixaban, clopidogrel, NSAIDs, t-PA), except aspirin (Exclusion)
Safety & Mental Health Screening
- 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 (Exclusion)
- Hospitalized or treated for suicidal behavior in the past 5 years (Exclusion)
- Current substance use disorder or positive urine drug screen (Exclusion)
Provider, Facility, & Process Requirements
- Prescriber is a VA (not VA Community care) board certified neurologist, geriatric psychiatrist, or geriatrician who specializes in treating dementia (Inclusion)
- Patient has a signed informed consent on file; if genotype testing is not performed, the patient and provider accept the risk (Inclusion)
- 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 (Inclusion)
- Facilities and providers need to enroll in the VA MedSAFE real-time medication use evaluation (MUE) for this medication (Inclusion)
Document 645: MON Donanemab azbt KISUNLA monograph Aug 2024
Indication
- Treatment of mild cognitive impairment (MCI) or mild dementia secondary to Alzheimer’s disease.
Patient Selection & Eligibility
- Age 60 to 85 years.
- Gradual and progressive change in memory function reported by participant or informant for > 6 months.
- Mini–Mental State Examination (MMSE) score of 20 to 28.
- Amyloid pathology (>37 Centiloids).
- Presence of tau pathology (low/medium or high on PET scan).
- Adequate literacy, vision, and hearing for neuropsychological testing.
- Stable concomitant symptomatic AD medications and other cognition-impacting medications for at least approximately 30 days prior to initiation.
Dosing & Administration
- Intravenous (IV) infusion over 30 minutes every 4 weeks.
- First three doses: 700 mg.
- Subsequent doses: 1400 mg every 4 weeks.
- Dose reduction to 700 mg if amyloid plaque level is 11 to <25 Centiloids.
- Switch to placebo if amyloid plaque level is <11 Centiloids on any single scan or 11 to <25 Centiloids on two consecutive scans.
Monitoring & Imaging Requirements
- Recent brain magnetic resonance imaging (MRI) required prior to initiating treatment.
- Periodic MRI monitoring required prior to the 2nd, 3rd, 4th, and 7th infusions.
- Amyloid PET scans performed at 24 and 52 weeks to assess amyloid plaque levels for dose adjustment or discontinuation.
Safety & Precautions
- Enhanced clinical vigilance for Amyloid-Related Imaging Abnormalities (ARIA) during the first 24 weeks of treatment.
- Increased risk of ARIA in apolipoprotein E e4 homozygotes compared to heterozygotes and noncarriers.
- Increased risk of ARIA-E and ARIA-H in patients with pretreatment microhemorrhages and/or superficial siderosis.
- Clinical evaluation including MRI if symptoms suggestive of ARIA occur.
- Infusion-related reactions: Reduce infusion rate or discontinue; consider pre-medication with antihistamines, acetaminophen, and/or corticosteroids at subsequent dosing.
Contraindications & Exclusions
- Significant neurological disease other than AD affecting cognition or study completion (e.g., other dementias, serious brain infection, Parkinson’s disease, multiple concussions, epilepsy/recurrent seizures except febrile childhood seizures).
- Current serious or unstable illnesses across cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic systems.
- History of cancer within the last 5 years (except non-metastatic basal/squamous cell carcinoma of skin, in situ cervical cancer, nonprogressive prostate cancer, or low-risk cancers).
- Psychiatric diagnosis likely to confound drug effect interpretation or cognitive assessment, or history of schizophrenia/chronic psychosis.
- Actively suicidal status.
- History of alcohol or drug use disorder within 2 years prior to screening (except tobacco use disorder).
- Clinically significant multiple/severe drug allergies, significant atopy, or severe posttreatment hypersensitivity reactions.
- Clinically important abnormality in physical/neurological exam, vital signs, ECG, or labs detrimental to participant.
- Contraindications for MRI or PET.
- MRI evidence of ARIA-E, >4 cerebral microhemorrhages, >1 area superficial siderosis, macro hemorrhage, or severe white matter disease.
- Elevated liver enzymes: ALT ≥2.5x ULN, AST ≥2.5x ULN, total bilirubin ≥1.5x ULN, or alkaline phosphatase ≥2x ULN.
- Prior passive anti-amyloid immunotherapy within <5 half-lives prior to initiation.
- Active immunization against Aβ in any other study.