Last Review Date: 11/05/2024

Date of Origin: 08/01/2024

Dates Reviewed: 08/2024, 11/2024

1. Length of Authorization

• Coverage will be provided for 6 months and may be renewed annually thereafter.

2. Dosing Limits

A. Quantity Limit (max daily dose) [NDC Unit]:

• Kisunla 350 mg/20 mL (17.5 mg/mL) solution in a single-dose vial: 2 vials every 4 weeks for three doses followed by 4 vials every 4 weeks thereafter

B. Max Units (per dose and over time) [HCPCS Unit]:

• 350 billable units every four weeks for the first three doses, followed by 700 billable units every four weeks thereafter.

3. Initial Approval Criteria ^1,5,6,9,11

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND
• Physician has assessed baseline disease severity utilizing at least ONE objective measure/tool (i.e., Mini-Mental Status Exam [MMSE], Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog-13/14], Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory-Mild Cognitive Impairment version [ADCS-ADL-MCI], Clinical Dementia Rating-Sum of Boxes [CDR-SB], Montreal Cognitive Assessment (MoCA), etc.); AND
• Patient does not have any of the following risk factors for intracerebral hemorrhage: findings suggestive of cerebral amyloid angiopathy (prior cerebral hemorrhage > 1 cm in greatest diameter, > 4 microhemorrhages, superficial siderosis, vasogenic edema); AND
• Patients receiving antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) prior to starting treatment with Kisunla have been on a stable dose for at least 4 weeks; AND
  • Patient has been tested prior to treatment to assess apolipoprotein E ε4 (ApoE ε4) status (e.g., homozygote, heterozygote, or noncarrier) and the prescriber has informed the patient that those who are homozygotes have a higher incidence of developing ARIA; OR
  • Genotype testing has not been performed and the prescriber has informed the patient that it cannot be determined if they are ApoE ε4 homozygotes and, therefore, if they are at higher risk for developing ARIA; AND

Universal Criteria ^1,5,6,9

• Must be prescribed by, or in consultation with, a specialist in neurology or gerontology; AND
• Patient has received a baseline brain magnetic resonance imaging (MRI) prior to initiating treatment and periodically throughout therapy (see prescribing information for schedule of MRI scans); AND
• Patient does not have a clinically significant and unstable psychiatric illness in the past 6 months; AND
• Patient does not have a history of alcohol or substance abuse in the preceding year; AND
• Will not be used concurrently with other anti-amyloid immunotherapies (i.e., lecanemab, aducanumab, etc.); AND

Alzheimer’s Disease (AD) † ^{1,2,5,6,11,12,13}

• Patient has a diagnosis of mild cognitive impairment (MCI) due to AD or has mild Alzheimer’s dementia (there is insufficient evidence in moderate or severe AD) AND both of the following:
  • Positron Emission Tomography (PET) scan positive for amyloid beta plaque or CSF assessment positive for hybrid ratios of Aβ 42/40, CSF p-tau 181/Aβ 42, or CSF t-tau/Aβ 42; AND
  • One of the following*:
    • Clinical Dementia Rating (CDR)-Global Score of 0.5-1.0 with Memory Box Score of at least 0.5; OR
    • MMSE score between 20-28, inclusive; OR
    • Montreal Cognitive Assessment (MoCA) score 18-25, inclusive; AND
• Other conditions mimicking, but of non-Alzheimer’s Dementia etiology, have been ruled out (e.g., vascular dementia, dementia with Lewy bodies [DLB], frontotemporal dementia [FTD], normal pressure hydrocephalus, etc.)

* Note: the aforementioned cognitive tests are typically the most commonly used but do NOT represent an exhaustive list. Use of alternative cognitive assessment tests not listed will be reviewed on a case-by-case basis.

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ^1,5,6

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: amyloid related imaging abnormalities-edema (ARIA-E) and -hemosiderin deposition (ARIA-H), intracerebral hemorrhage, severe hypersensitivity reactions including anaphylaxis, etc.; AND
• Patient has responded to therapy compared to pretreatment baseline as evidenced by improvement, stability, or slowing in cognitive and/or functional impairment in one or more of the following (not all-inclusive): ADAS-Cog 13/14; ADCS-ADL-MCI; MMSE; CDR-SB, MoCA, etc.; AND
• Patient will discontinue treatment when reduction of amyloid plaques are reduced to minimal levels on amyloid PET imaging, defined as either of the following:
  • Level is <11 Centiloids on a single PET scan; OR
  • Level is 11 to <25 Centiloids on two consecutive PET scans; AND
• Patient has not progressed to moderate or severe AD; AND
• Patient has received a pre- 2^nd, 3^rd, 4^th, AND 7^th infusion MRI for monitoring of Amyloid Related Imaging Abnormalities-edema (ARIA-E) and Amyloid Related Imaging Abnormalities-hemosiderin (ARIA-H) microhemorrhages; AND

ARIA-E §

• Patient is asymptomatic or mildly symptomatic* with mild radiographic severity** on MRI; OR
• Patient is asymptomatic or mildly symptomatic* with moderate to severe radiographic severity** on MRI AND administration will be suspended until MRI demonstrates radiographic resolution and symptoms, if present, resolve; OR
• Patient has moderate to severe symptoms* with mild to severe radiographic severity** on MRI AND administration will be suspended until MRI demonstrates radiographic resolution and symptoms, if present, resolve

ARIA-H §

• • Patient is asymptomatic with mild radiographic severity** on MRI; OR
  • Patient is asymptomatic with moderate radiographic severity** on MRI AND administration will be suspended until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; OR
  • Patient is symptomatic with mild to moderate radiographic severity** on MRI AND administration will be suspended until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; OR
  • Patient has severe radiographic severity** on MRI AND administration will be suspended until MRI demonstrates radiographic stabilization and symptoms, if present, resolve

§ Clinical judgment will be used in considering whether to continue treatment or permanently discontinue. In patients who develop intracerebral hemorrhage greater than 1 cm in diameter during treatment from Kisunla, suspend dosing until MRI demonstrates radiographic stabilization and symptoms, if present, resolve. Consider a follow-up MRI to assess for resolution 2 to 4 months after initial identification.

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J0175 – Injection, donanemab-azbt, 2 mg: 1 billable unit = 2 mg

NDC:

• Kisunla 350 mg/20 mL (17.5 mg/mL) solution in a single-dose vial: 00002-9401-xx

7. References

1. Kisunla [package insert]. Indianapolis, IN; Eli Lilly, Inc; July 2024. Accessed October 2024.
2. McKhann GM, Knopman DS, Chertklow 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. Epub 2011 Apr 21. 
3. Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of 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):280. Epub 2011 Apr 21.
4. Mintun M, Ritchie CW, Solomon P, et al. Donanemab in Early Symptomatic Alzheimer’s Disease: Efficacy and Safety in TRAILBLAZER-ALZ 2, a Phase 3 Randomized Clinical Trial. Alzheimer's Dement., 19: e082733. https://doi.org/10.1002/alz.082733.
5. Salloway S, Lee E, Papka M, Pain A, Oru E, Ferguson M, et al. TRAILBLAZER-ALZ 4: Topline study results directly comparing donanemab to aducanumab on amyloid lowering in early, symptomatic Alzheimer’s disease (S26.009). Neurology. 2023;100(17 Supplement 2):3126.
6. Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. Jama. 2023.
7. O'Bryant SE, Lacritz LH, Hall J, et al. Validation of the new interpretive guidelines for the clinical dementia rating scale sum of boxes score in the national Alzheimer's coordinating center. Arch Neurol. 2010 Jun;67(6):746-9. doi: 10.1001/archneurol.2010.115.
8. Skinner J, Carvalho, JO, Potter GG, et al. The Alzheimer's Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-Plus): an expansion of the ADAS-Cog to improve responsiveness in MCI. Brain Imaging Behav. 2012 Dec;6(4):489-501. doi: 10.1007/s11682-012-9166-3.
9. Lin GA, Whittington MD, Synnott PG, et al. Aducanumab for Alzheimer’s Disease: Effectiveness and Value; Final Evidence Report and Meeting Summary. Institute for Clinical and Economic Review, August 5, 2021. https://icer.org/assessment/alzheimers-disease-2021/.
10. Lin GA, Whittington MD, Wright A, et al. Beta-Amyloid Antibodies for Early Alzheimer’s Disease: Effectiveness and Value; Draft Evidence Report. Institute for Clinical and Economic Review, December 22, 2022. https://icer.org/assessment/alzheimers-disease-2022/#timeline.
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: 5143–5169. https://doi.org/10.1002/alz.13859.
12. Tahami Monfared AA, Houghton K, Zhang Q, Mauskopf J; Alzheimer’s Disease Neuroimaging Initiative. Staging Disease Severity Using the Alzheimer's Disease Composite Score (ADCOMS): A Retrospective Data Analysis. Neurol Ther. 2022 Mar;11(1):413-434. doi: 10.1007/s40120-022-00326-y. Epub 2022 Jan 31. Erratum in: Neurol Ther. 2022 Jun;11(2):915-927. doi: 10.1007/s40120-022-00340-0. PMID: 35099758; PMCID: PMC8857364.
13. Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCA/LCD): N/A