Indications for Kisunla (Donanemab)
Kisunla (donanemab-azbt) is indicated for the treatment of Alzheimer's disease in adults with mild cognitive impairment or mild dementia stage of disease (early symptomatic AD) who have confirmed amyloid beta pathology. 1
Core Eligibility Requirements
The FDA-approved indication is straightforward but requires meeting specific criteria before treatment initiation:
Disease Stage
- Mild cognitive impairment (MCI) due to AD OR mild dementia due to AD (Clinical Stages 3-4, typically MMSE 20-30) 2
- Treatment must be initiated during the early symptomatic phase—this is the population studied in clinical trials 1
- Not indicated for asymptomatic individuals or moderate-to-severe dementia 3
Biomarker Confirmation Required
Amyloid pathology must be confirmed before starting treatment using one of the following 1, 2:
- Amyloid PET imaging (preferred method, lower false-negative rate) 4
- CSF biomarkers (acceptable alternative)
Tau PET is not required for eligibility, though it may provide additional prognostic information 2
Critical Pre-Treatment Assessments
Mandatory Testing Before Initiation
ApoE ε4 genotyping must be performed to stratify ARIA risk 1, 5:
- Homozygotes have substantially higher risk of symptomatic and serious ARIA
- This information is essential for shared decision-making about treatment risks versus benefits
- In the European Union, donanemab is specifically indicated only for non-carriers or heterozygotes 6
Baseline brain MRI (within 12 months of treatment start) to exclude patients with 1, 2:
- More than 4 cerebral microbleeds (CMBs)
- Any cortical superficial siderosis (cSS)—though donanemab trials permitted one focus
- Evidence of intracerebral hemorrhage (ICH)
- Major vascular contribution to cognitive impairment
Important Exclusion Criteria
Patients should be excluded if they have 5:
- Probable cerebral amyloid angiopathy (CAA) based on Boston criteria v2.0 (≥2 hemorrhagic markers)
- Uncontrolled hypertension
- Current anticoagulant use
- Known serious hypersensitivity to donanemab or excipients 1
The presence of concomitant CAA creates substantial risk for ARIA, and careful risk-benefit assessment is mandatory before proceeding 5
Clinical Context and Implementation
Why Biomarker Confirmation Matters
Disease-modifying treatments like donanemab target the underlying amyloid pathology, so confirming its presence is essential 3. Up to 92% of MCI patients remain undiagnosed or misdiagnosed in primary care, and even specialist diagnoses change in 36% of cases after amyloid PET 3, 7. Without biomarker confirmation, you risk treating non-AD causes of cognitive impairment.
Shared Decision-Making Framework
The decision to initiate therapy must be grounded in shared decision-making that emphasizes 2:
- Patient's values and goals of care
- Understanding of modest clinical benefits (slowing rather than reversing decline)
- ARIA risks stratified by ApoE ε4 status
- Commitment to required monitoring schedule
- Financial and logistical considerations
Common Pitfalls to Avoid
- Do not initiate treatment without biomarker-confirmed amyloid pathology—clinical diagnosis alone is insufficient 1, 3
- Do not skip ApoE ε4 genotyping—this is mandatory for risk stratification 1
- Do not treat patients beyond mild dementia stage—efficacy data only exist for early symptomatic disease 1
- Do not overlook hemorrhagic markers on baseline MRI—these predict ARIA risk 5, 2
Treatment Course Considerations
While not part of the formal indication, clinicians should understand that:
- Treatment involves monthly IV infusions with escalating doses 1
- Stopping criteria exist: Consider discontinuing when amyloid plaques are reduced to minimal levels on repeat amyloid PET (typically 12-18 months) 1, 2
- Surveillance MRIs are required prior to the 2nd, 3rd, 4th, and 7th infusions to monitor for ARIA 1, 2
The indication reflects a paradigm shift toward disease-modifying treatment in AD, but success requires meticulous patient selection, biomarker confirmation, and safety monitoring 3.