Clinical Policy: Donanemab-azbt (Kisunla) Form

CENTENE Corporation

Clinical Policy: Donanemab-azbt (Kisunla) Reference Number: CP.PHAR.594 Effective Date: 07.02.24 Last Review Date: 05.26 Line of Business: Commercial, HIM/ICHRA, Medicaid

Coding Implications Revision Log

See Important Reminder at the end of this policy for important regulatory and legal information.

Description Donanemab-azbt (Kisunla™) is a monoclonal antibody targeting amyloid beta.

FDA Approved Indication(s) Kisunla is indicated for the treatment of Alzheimer’s disease (AD). Treatment with Kisunla should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in the clinical trials.

B. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace/ICHRA and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace/ICHRA and CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid.

B. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace/ICHRA and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace/ICHRA and CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid.

III.Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid, or evidence of coverage documents.

IV.Appendices/General Information Appendix A: Abbreviation/Acronym Key AD: Alzheimer’s disease ARIA-E: amyloid-related imaging abnormalities-edema ARIA-H: amyloid-related imaging abnormalities-hemosiderin deposition CDR-SB: Clinical Dementia Rating- Sum of Boxes CMS: Centers for Medicare and Medicaid Services DLB: dementia with Lewy bodies FAQ: Functional Assessment Questionnaire FAST: Functional Assessment Staging Test FDA: Food and Drug Administration FLAIR: fluid attenuation inversion recovery FTD: frontotemporal dementia IADL: instrumental activity of daily living MCI: mild cognitive impairment MMSE: Mini-Mental State Examination MoCA: Montreal Cognitive Assessment MRI: magnetic resonance imaging PPA: primary progressive aphasia TIA: transient ischemic attack

Appendix B: Therapeutic Alternatives Not applicable

Appendix C: Contraindications/Boxed Warnings • Contraindication(s): serious hypersensitivity to donanemab-azbt or to any of the excipients of Kisunla • Boxed warning(s): increased risk of ARIA

Appendix D: Dementia Rating Scales • MoCA is a highly sensitive tool for early detection of MCI and has been widely adopted in clinical settings. The maximum score is 30 points. The following ranges may be used to grade severity: 18-25 = mild cognitive impairment, 10-17 = moderate cognitive impairment and < 10 = severe cognitive impairment. However, research for these severity ranges has not been established yet. The average MoCA score for MCI is 22 (range 19- 25) and the average MoCA score for Mild AD is 16 (range 11-21). • 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 with a score of: ○ 25 to 30 suggests normal cognition, ○ 21 to 24 suggests mild dementia, ○ 13 to 20 suggests moderate dementia, and ○ 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. • The FAQ measures instrumental activities of daily living (IADLs), such as preparing balanced meals and managing personal finances. Since functional changes are noted earlier in the dementia process with IADLs that require a higher cognitive ability compared to basic activities of daily living, this tool is useful to monitor these functional changes over time. The score range is 0-30. A cut-point of 9 (dependent in 3 or more activities) is recommended to indicate impaired function and possible cognitive impairment. • FAST is a measure commonly used to assess functional status in patients with dementia. It provides a comprehensive evaluation of functional ability and the potential for a functional decline over time, including physical functional abilities (dressing and grooming), functional language abilities (memory and recognition), and functional activities such as mobility or self-feeding. The FAST score ranges from 1 to 7, categorizing the stages of AD into one of the below: ○ 1: normal aging ○ 2: possible mild cognitive impairment ○ 3: mild cognitive impairment ○ 4: mild dementia ○ 5: moderate dementia ○ 6: moderately severe dementia ○ 7: severe dementia • CDR-SB assessment is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer’s disease and related dementias: memory, orientation, judgment, and problem solving, community affairs, home and 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

Appendix E: Diagnosis of Alzheimer’s Disease • AD ○ Interference with ability to function at work or at usual activities ○ A decline from a previous level of functioning and performing ○ Not explained by delirium or major psychiatric disorder ○ Cognitive impairment established by history-taking from the patient and a knowledgeable informant; and objective bedside mental status examination or neuropsychological testing ○ Cognitive impairment involves a minimum of two of the following domains: ■ Impaired ability to acquire and remember new information ■ Impaired reasoning and handling of complex tasks, poor judgment ■ Impaired visuospatial abilities ■ Impaired language functions (speaking, reading, writing) ■ Changes in personality, behavior, or comportment ○ Insidious onset (gradual onset over months to years, not over hours to days) ○ Clear-cut history of worsening ○ Initial and most prominent cognitive deficits are one of the following: ■ Amnestic presentation (impairment in learning and recall of recently learned information) ■ Nonamnestic presentation in either a language presentation (prominently word- finding deficits), a visuospatial presentation with visual deficits, or executive dysfunction (prominently impaired reasoning, judgment and/or problem solving) ○ No evidence of substantial concomitant cerebrovascular disease, core features of dementia with Lewy bodies (DLB), prominent features of behavioral variant frontotemporal dementia (FTD) or prominent features of semantic or nonfluent/agrammatic variants of primary progressive aphasia (PPA), or evidence of another concurrent, active neurologic or non-neurologic disease or use of medication that could have a substantial effect on cognition • Mild cognitive impairment due to AD – core clinical criteria ○ Concern regarding change in cognition obtained from the patient, from an informant who knows the patient well, or from a skilled clinician observing the patient ○ Objective evidence of impairment in one or more cognitive domains that is not explained by age or education ○ Preservation of independence in functional abilities ○ Not demented • Although tests for blood-based biomarkers are now available to aid in diagnosing Alzheimer’s disease, their proper use in clinical practice is unestablished. They are not currently able to fully replace the need for confirmatory testing with positron emission tomography scan or cerebrospinal fluid testing, and as such, their ability to determine eligibility for treatment with Kisunla is unconfirmed.

V. Dosage and Administration

VI. Product Availability Single-dose vial for injection: 350 mg/20 mL

VII.References

1. Kisunla Prescribing Information. Indianapolis, IN: Eli Lilly and Co.; July 2025. Available at: https://pi.lilly.com/us/kisunla-uspi.pdf?s=pi. Accessed July 15, 2025.
2. Mintun MA, Lo AC, Duggan Evans C, et al. Donanemab in early Alzheimer’s disease. N Engl J Med 2021;384:1691-1704. doi: 10.1056/NEJMoa2100708.
3. Sims JR, Zimmer JA, Evans CD, et al. Donanemab in early symptomatic Alzheimer disease – the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA 2023; published online: July 17, 2023. doi:10.1001/jama.2023.13239.
4. Centers for Medicare & Medicaid Services. Monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease. Medicare National Coverage Determination. 200.3;
5. Available at: https://www.cms.gov/medicare-coverage- database/view/ncd.aspx?ncdid=375&ncdver=1. Accessed July 11, 2024.
6. Andrews JS, Desai U, Kirson NY, et al. Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer’s disease clinical trials. Alzheimer’s & Dementia 2019 Aug;5:354-63.
7. Trzepacz PT, Hochstetler H, Wang S, et al. Relationship between the Montreal Cognitive Assessment and Mini-Mental State Examination for assessment of mild cognitive impairment in older adults. BMC Geriatrics 2015;15:107. https://doi.org/10.1186/s12877-015-0103-3.
8. O’Bryant SE, Waring SC, Cullum CM, et al. Staging dementia using Clinical Dementia Rating Scale Sum of Boxes Scores: a Texas Alzheimer’s Research Consortium study. Arch Neurol 2008 August;65(8):1091–1095. doi:10.1001/archneur.65.8.1091.
9. Palmqvist S, Whitson HE, Allen LA, et al. Alzheimer’s Association clinical practice guidelines on the use of blood-based biomarkers in the diagnostic workup of suspected Alzheimer’s disease within specialized care settings. Alzheimer’s Dement. 2025;21:e70535. doi: 10.1002/alz.70535.
10. Atri A, Dickerson BC, Clevenger C, et al. Alzheimer’s Association clinical practice guideline for the diagnostic evaluation, testing, counseling, and disclosure of suspected Alzheimer’s disease and related disorders (DETeCD-ADRD): executive summary of recommendations for primary care. Alzheimer’s Dement. 2025;21:e14333. doi: 10.1002/alz.14333.
11. Jack CR, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimer’s Dement. 2024;20:5143-69. doi: 10.1002/alz.13859.

Coding Implications Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to- date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.

Reviews, Revisions, and Approvals

Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions, and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures.

This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time.

This clinical policy does not constitute medical advice, medical treatment, or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions.

Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over to whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members, and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services.

Note: For Medicaid members, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.

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