WHA

Monoclonal Antibody Agents for Alzheimer's Disease - PA, NF

Indications for Prior Authorization

Aduhelm (aducanumab-avwa)
  • For diagnosis of Alzheimer's Disease
    Indicated for the treatment of Alzheimer's disease. Treatment with Aduhelm should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with Aduhelm. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).

Kisunla (donanemab-azbt)
  • For diagnosis of Alzheimer's Disease
    Indicated for the treatment of Alzheimer’s disease. Treatment with Kisunla should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in the clinical trials.

Leqembi (lecanemab-irmb intravenous solution), Leqembi IQLIK (lecanemab-irmb subcutaneous solution)
  • For diagnosis of Alzheimer's Disease
    Indicated for the treatment of Alzheimer’s disease. Treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.

Criteria

Aduhelm

Prior Authorization, Non-Formulary (Initial Authorization)

Length of Approval: 6 Month(s)
For diagnosis of Alzheimer's Disease

  • Both of the following:
    • Based on the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria, one of the following: [16,17,24]
      • Diagnosis of mild cognitive impairment due to Alzheimer's disease
      • Diagnosis of probable Alzheimer's disease dementia
      AND
    • Submission of medical records (e.g., chart notes) confirming both of the following: [18-19]
      • Clinical Dementia Rating-Global (CDR-G) score of 0.5 or Clinical Dementia Rating Sum of Boxes (CDR-SB) score of 0.5-4
      • Mini-Mental State Examination score of 24-30
    AND
  • Submission of medical records (e.g., chart notes) confirming the presence of beta-amyloid protein deposition, as evidenced by one of the following:
    • Positive amyloid positron emission tomography (PET) scan
      • OR
    • Both of the following:
      • Attestation that the patient does not have access to amyloid PET scanning
      • Cerebrospinal fluid (CSF) biomarker or blood testing documents abnormalities suggestive of beta-amyloid accumulation (e.g., Aβ42 level, Aβ42:Aβ40 ratio)
    AND
  • Provider attests that the patient's ApoE e4 carrier status is known prior to initiating treatment and a shared decision-making conversation regarding the results has been completed
    • AND
  • Other differential diagnoses (e.g., dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), vascular dementia, pseudodementia due to mood disorder, vitamin B12 deficiency, encephalopathy, etc.) have been ruled out
    • AND
  • Both of the following: [18-19]
    • Patient is not currently taking an anticoagulant or antiplatelet agent (unless aspirin 325 mg/day or less)
    • Patient has no history of transient ischemic attack (TIA) or stroke within previous year prior to initiating treatment
    AND
  • Counseling has been provided on the risk of amyloid-related imaging abnormalities (ARIA-E and ARIA-H) and patient and/or caregiver are aware to monitor for headache, dizziness, visual disturbances, nausea, and vomiting [20]
    • AND
  • Submission of medical records (e.g., chart notes) confirming a baseline brain magnetic resonance imaging (MRI) has been completed within 12 months prior to initiating treatment
    • AND
  • Not used in combination with other Aβ monoclonal antibodies (mAbs) for Alzheimer's Disease (e.g., Leqembi)
    • AND
  • Prescribed by a neurologist, geriatrician, or geriatric psychiatrist
Aduhelm

Prior Authorization, Non-Formulary (Reauthorization)

Length of Approval: 6 Month(s)
For diagnosis of Alzheimer's Disease

  • Patient is benefitting from therapy as defined by both of the following:
    • Based on the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria, one of the following: [16,17,24]
      • Patient continues to have a diagnosis of mild cognitive impairment due to Alzheimer's disease
      • Patient continues to have a diagnosis of probable Alzheimer's disease dementia
      AND
    • Submission of medical records (e.g., chart notes) confirming both of the following: [18-19]
      • Clinical Dementia Rating-Global (CDR-G) score of 0.5 or Clinical Dementia Rating Sum of Boxes (CDR-SB) score of 0.5-4
      • Mini-Mental State Examination score of 24-30
    AND
  • Submission of medical records (e.g., chart notes) confirming follow-up brain magnetic resonance imaging (MRI) has been completed after the initiation of therapy prior to the 5th infusion treatment to show one of the following:
    • Both of the following:
      • Less than 10 new incident microhemorrhages
      • 2 or less focal areas of superficial siderosis
      OR
    • If 10 or more new incident microhemorrhages or greater than 2 focal areas of superficial siderosis are present then both of the following:
      • Patient has been clinically evaluated for ARIA related signs or symptoms (e.g., dizziness, visual disturbances)
      • Follow-up MRI demonstrates radiographic stabilization (i.e., no increase in size or number of ARIA-H)
    AND
  • Not used in combination with other Aβ monoclonal antibodies (mAbs) for Alzheimer's Disease (e.g., Leqembi)
    • AND
  • Prescribed by a neurologist, geriatrician, or geriatric psychiatrist
Kisunla

Prior Authorization, Non-Formulary (Initial Authorization)

Length of Approval: 6 Month(s)
For diagnosis of Alzheimer's Disease

  • Both of the following:
    • Diagnosis of one of the following, based on the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria:
      • Mild cognitive impairment due to Alzheimer's disease
      • Mild dementia due to Alzheimer's disease
      AND
    • Submission of medical records (e.g., chart notes) confirming Mini-Mental State Examination score of 20-28
    AND
  • Submission of medical records (e.g., chart notes) confirming the presence of beta-amyloid protein deposition, as evidenced by one of the following:
    • Positive amyloid positron emission tomography (PET) scan
    • Attestation that patient does not have access to amyloid PET scanning and cerebrospinal fluid (CSF) biomarker testing documents abnormalities suggestive of beta-amyloid accumulation (e.g., Aβ42 level, Aβ42:Aβ40 ratio, Tau, p-Tau)
    AND
  • Both of the following:
    • Provider attests that testing regarding the patient's ApoE e4 carrier status has been performed prior to initiating treatment
    • Prior to testing, a shared decision-making conversation has occurred, regarding the risk of amyloid-related imaging abnormalities (ARIA), across genotypes, and the implications of genetic testing results
    AND
  • Submission of medical records (e.g., chart notes) confirming a baseline brain magnetic resonance imaging (MRI) has been completed within 12 months prior to initiating treatment
    • AND
  • Other differential diagnoses (e.g., dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), vascular dementia, pseudodementia due to mood disorder, vitamin B12 deficiency, encephalopathy) have been ruled out
    • AND
  • Both of the following:
    • Patient is not currently taking an anticoagulant (e.g., warfarin, dabigatran)
    • Patient has no history of intracerebral hemorrhage (e.g., transient ischemic attack [TIA], stroke) prior to initiating treatment
    AND
  • Not used in combination with other Aβ monoclonal antibodies (mAbs) for Alzheimer's Disease (e.g., Aduhelm, Leqembi)
    • AND
  • Counseling has been provided on the risk of amyloid-related imaging abnormalities (ARIA-E and ARIA-H) and patient and/or caregiver are aware to monitor for headache, dizziness, visual disturbances, nausea, and vomiting
    • AND
  • Provider will enroll patient in a registry [e.g., Alzheimer's Network for Treatment and Diagnostics (ALZ-Net)]
    • AND
  • Patient is not being treated with Kisunla as part of a clinical trial
    • AND
  • Prescribed by a neurologist, geriatrician, or geriatric psychiatrist
Kisunla

Prior Authorization, Non-Formulary (Reauthorization)

Length of Approval: 6 Month(s)
For diagnosis of Alzheimer's Disease

  • Both of the following:
    • Patient continues to have one of the following diagnoses based on the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria:
      • Mild cognitive impairment due to Alzheimer's disease
      • Mild dementia due to Alzheimer's disease
      AND
    • Submission of medical records (e.g., chart notes) confirming Mini-Mental State Examination score of 20-28
    AND
  • Submission of medical records (e.g., chart notes) confirming that at least one amyloid PET brain scan is performed every 6 months and the result is positive for amyloid based on visual read [A]
    • AND
  • Submission of medical records (e.g., chart notes) confirming follow-up brain magnetic resonance imaging (MRI) has been completed after the initiation of therapy prior to the 5th and 7th infusion treatment to show one of the following radiographic evidence of amyloid related imaging abnormalities (i.e, ARIA-E, ARIA-H):
    • Patient has mild radiographic severity of Aria – E on MRI and is asymptomatic
    • Patient has mild radiographic severity of Aria – E on MRI and has mild clinical symptoms
    • Patient has mild radiographic severity of Aria-H on MRI and is asymptomatic
    • ARIA (i.e. ARIA E, ARIA H) has not been observed on MRI
    AND
  • Not used in combination with other Aβ monoclonal antibodies (mAbs) for Alzheimer's Disease (e.g., Aduhelm, Leqembi)
    • AND
  • Patient is not being treated with Kisunla as part of a clinical trial
    • AND
  • Prescribed by a neurologist, geriatrician, or geriatric psychiatrist
Leqembi Intravenous solution

Prior Authorization, Non-Formulary (Initial Authorization)

Length of Approval: 6 Month(s)
For diagnosis of Alzheimer's Disease

  • Both of the following:
    • Diagnosis of one of the following, based on the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria:
      • Mild cognitive impairment due to Alzheimer's disease
      • Mild dementia due to Alzheimer's disease
      AND
    • Submission of medical records (e.g., chart notes) confirming all of the following [12-13]:
      • Global Clinical Dementia Rating (CDR) score of 0.5 or 1.0
      • CDR Memory Box score of 0.5 or greater
      • Mini-Mental State Examination score of 22 or greater
    AND
  • Submission of medical records (e.g., chart notes) confirming the presence of beta-amyloid protein deposition, as evidenced by one of the following:
    • Positive amyloid positron emission tomography (PET) scan
    • Attestation that patient does not have access to amyloid PET scanning and cerebrospinal fluid (CSF) biomarker testing documents abnormalities suggestive of beta-amyloid accumulation (e.g., Aβ42 level, Aβ42:Aβ40 ratio, Tau, p-Tau)
    AND
  • Both of the following:
    • Provider attests that testing regarding the patient's ApoE e4 (apolipoproteinE e4) carrier status has been performed prior to initiating treatment
    • Prior to testing, a shared decision-making conversation has occurred, regarding the risk of amyloid-related imaging abnormalities (ARIA), across genotypes, and the implications of genetic testing results
    AND
  • Submission of medical records (e.g., chart notes) confirming a baseline brain magnetic resonance imaging (MRI) has been completed within 12 months prior to initiating treatment
    • AND
  • Other differential diagnoses (e.g., dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), vascular dementia, pseudodementia due to mood disorder, vitamin B12 deficiency, encephalopathy) have been ruled out
    • AND
  • Both of the following [9, 12-13]:
    • Patient is not currently taking an anticoagulant (e.g., warfarin, dabigatran)
    • Patient has no history of intracerebral hemorrhage (e.g., transient ischemic attack [TIA], stroke) prior to initiating treatment
    AND
  • Not used in combination with other Aβ monoclonal antibodies (mAbs) for Alzheimer's Disease (e.g., Aduhelm, Kisunla)
    • AND
  • Counseling has been provided on the risk of amyloid-related imaging abnormalities (ARIA-E and ARIA-H) and patient and/or caregiver are aware to monitor for headache, confusion, dizziness, visual changes, nausea, and gait difficulty
    • AND
  • Provider will enroll patient in a registry [e.g., Alzheimer's Network for Treatment and Diagnostics (ALZ-Net)]
    • AND
  • Patient is not being treated with Leqembi as part of a clinical trial
    • AND
  • Prescribed by a neurologist, geriatrician, or geriatric psychiatrist
Leqembi Intravenous solution

Prior Authorization, Non-Formulary (Reauthorization)

Length of Approval: 6 Month(s)
For diagnosis of Alzheimer's Disease

  • Both of the following:
    • Patient continues to have one of the following diagnoses based on the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria:
      • Mild cognitive impairment due to Alzheimer's disease
      • Mild dementia due to Alzheimer's disease
      AND
    • Submission of medical records (e.g., chart notes) confirming all of the following [12-13]:
      • Global Clinical Dementia Rating (CDR) score of 0.5 or 1.0
      • CDR Memory Box score of 0.5 or greater
      • Mini-Mental State Examination score of 22 or greater
    AND
  • Submission of medical records (e.g., chart notes) confirming follow-up brain magnetic resonance imaging (MRI) has been completed after the initiation of therapy prior to the 5th and 7th infusion treatment to show one of the following radiographic evidence of amyloid related imaging abnormalities (i.e, ARIA-E, ARIA-H):
    • Patient has mild radiographic severity of Aria – E on MRI and is asymptomatic
    • Patient has mild radiographic severity of Aria – E on MRI and has mild clinical symptoms
    • Patient has mild radiographic severity of Aria-H on MRI and is asymptomatic
    • ARIA (i.e. ARIA E, ARIA H) has not been observed on MRI
    AND
  • Not used in combination with other Aβ monoclonal antibodies (mAbs) for Alzheimer's Disease (e.g., Aduhelm, Kisunla)
    • AND
  • Patient is not being treated with Leqembi as part of a clinical trial
    • AND
  • Prescribed by a neurologist, geriatrician, or geriatric psychiatrist
Leqembi IQLIK Subcutaneous solution

Prior Authorization, Non-Formulary (Initial Authorization)

Length of Approval: 6 Month(s)
For diagnosis of Alzheimer's Disease

  • Both of the following:
    • Diagnosis of one of the following, based on the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria:
      • Mild cognitive impairment due to Alzheimer's disease
      • Mild dementia due to Alzheimer's disease
      AND
    • Submission of medical records (e.g., chart notes) confirming all of the following [12-13]:
      • Global Clinical Dementia Rating (CDR) score of 0.5 or 1.0
      • CDR Memory Box score of 0.5 or greater
      • Mini-Mental State Examination score of 22 or greater
    AND
  • Submission of medical records (e.g., chart notes) confirming the presence of beta-amyloid protein deposition, as evidenced by one of the following:
    • Positive amyloid positron emission tomography (PET) scan
    • Attestation that patient does not have access to amyloid PET scanning and cerebrospinal fluid (CSF) biomarker testing documents abnormalities suggestive of beta-amyloid accumulation (e.g., Aβ42 level, Aβ42:Aβ40 ratio, Tau, p-Tau)
    AND
  • Both of the following:
    • Provider attests that testing regarding the patient's ApoE e4 (apolipoproteinE e4) carrier status has been performed prior to initiating treatment
    • Prior to testing, a shared decision-making conversation has occurred, regarding the risk of amyloid-related imaging abnormalities (ARIA), across genotypes, and the implications of genetic testing results
    AND
  • Submission of medical records (e.g., chart notes) confirming a baseline brain magnetic resonance imaging (MRI) has been completed within 12 months prior to initiating treatment
    • AND
  • Other differential diagnoses (e.g., dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), vascular dementia, pseudodementia due to mood disorder, vitamin B12 deficiency, encephalopathy) have been ruled out
    • AND
  • Both of the following [9, 12-13]:
    • Patient is not currently taking an anticoagulant (e.g., warfarin, dabigatran)
    • Patient has no history of intracerebral hemorrhage (e.g., transient ischemic attack [TIA], stroke) prior to initiating treatment
    AND
  • Not used in combination with other Aβ monoclonal antibodies (mAbs) for Alzheimer's Disease (e.g., Aduhelm, Kisunla)
    • AND
  • Counseling has been provided on the risk of amyloid-related imaging abnormalities (ARIA-E and ARIA-H) and patient and/or caregiver are aware to monitor for headache, confusion, dizziness, visual changes, nausea, and gait difficulty
    • AND
  • Provider will enroll patient in a registry [e.g., Alzheimer's Network for Treatment and Diagnostics (ALZ-Net)]
    • AND
  • Patient is not being treated with Leqembi as part of a clinical trial
    • AND
  • Will be used as a maintenance dose following completion of 18 months with the intravenous initiation phase
    • AND
  • Prescribed by a neurologist, geriatrician, or geriatric psychiatrist
Leqembi IQLIK Subcutaneous solution

Prior Authorization, Non-Formulary (Reauthorization)

Length of Approval: 6 Month(s)
For diagnosis of Alzheimer's Disease

  • Both of the following:
    • Patient continues to have one of the following diagnoses based on the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria:
      • Mild cognitive impairment due to Alzheimer's disease
      • Mild dementia due to Alzheimer's disease
      AND
    • Submission of medical records (e.g., chart notes) confirming all of the following [12-13]:
      • Global Clinical Dementia Rating (CDR) score of 0.5 or 1.0
      • CDR Memory Box score of 0.5 or greater
      • Mini-Mental State Examination score of 22 or greater
    AND
  • Submission of medical records (e.g., chart notes) confirming follow-up brain magnetic resonance imaging (MRI) has been completed after the initiation of therapy prior to the 5th and 7th infusion treatment to show one of the following radiographic evidence of amyloid related imaging abnormalities (i.e, ARIA-E, ARIA-H):
    • Patient has mild radiographic severity of Aria – E on MRI and is asymptomatic
    • Patient has mild radiographic severity of Aria – E on MRI and has mild clinical symptoms
    • Patient has mild radiographic severity of Aria-H on MRI and is asymptomatic
    • ARIA (i.e. ARIA E, ARIA H) has not been observed on MRI
    AND
  • Not used in combination with other Aβ monoclonal antibodies (mAbs) for Alzheimer's Disease (e.g., Aduhelm, Kisunla)
    • AND
  • Patient is not being treated with Leqembi as part of a clinical trial
    • AND
  • Prescribed by a neurologist, geriatrician, or geriatric psychiatrist

  • Guideline ID
    GL-261196

  • Formulary
    Premium

  • Effective date
    Sep 5, 2025

  • P&T approval date
    Feb 18, 2021

P & T Revisions

2025-09-04, 2024-08-01, 2024-04-24, 2023-05-03, 2023-03-31, 2023-02-16, 2022-06-01, 2022-04-25, 2021-06-24, 2021-06-16

  1. Kisunla Prescribing Information. Eli Lilly and Company. Indianapolis, IN. July 2024.
  2. Alzheimer’s Association: Criteria for Diagnosis and Staging of Alzheimer’s Disease. Available at: https://www.alz.org/research/for_researchers/diagnostic-criteria-guidelines. Accessed July 22, 2024.
  3. Jack Jr, Clifford, Andrews, J Scott, Beach, T., et al. Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Available at: https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.13859. Accessed July 22, 2024.
  4. Barthelemy, N., Salvado, G., Schindler, S., et al. Highly accurate blood test for Alzheimer’s disease is similar or superior to clinical cerebrospinal fluid tests. Available at: https://www.nature.com/articles/s41591-024-02869-z. Accessed July 22, 2024.
  5. Schneider, Tamara. Alzheimer’s blood test performs as well as FDA- approved spinal fluid tests. Available at: https://medicine.wustl.edu/news/alzheimers-blood-test-performs-as-well-as-fda-approved-spinal-fluid-tests/. Accessed July 22, 2024.
  6. AlMansoori, M., Jemimah, S., Abuhantash, F., et al. Predicitng early Alzheimer’s with blood biomarkers and clinical features. Available at: https://www.nature.com/articles/s41598-024-56489-1. Accessed July 22, 2024.
  7. Sims, J., Zimmer, J., Evans, C., et al. Donanemab in Early Symptomatic Alzheimer Disease, The Trailblazer-ALZ 2 Randomized Clinical Trial. Available at: Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial | Dementia and Cognitive Impairment | JAMA | JAMA Network. Accessed July 22, 2024.
  8. ClinicalTrials.gov. A Study of Donanemab (LY3002813) in Participants With Early Alzheimer's Disease (TRAILBLAZER-ALZ 2). Available at: https://clinicaltrials.gov/study/NCT04437511#participation-criteria. Accessed July 22, 2024.
  9. Leqembi Prescribing Information. Eisai, Inc. Nutley, NJ. August 2025.
  10. McKhann GM, Knopman DS, Chertkow 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):263-269.
  11. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment 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):270-279.
  12. A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease (Clarity AD): https://www.clinicaltrials.gov/ct2/show/NCT03887455. Accessed January 6, 2023.
  13. A study to Evaluate Safety, Tolerability, and Efficacy of Lecanemab in Subjects with Early Alzheimer’s Disease. https://www.clinicaltrials.gov/ct2/show/NCT01767311. Accessed January 6, 2023.
  14. Oudart, Jean., Djerada, Z., et al. Incremental Value of CSF Biomarkers in Clinically Diagnosed AD and Non-AD Dementia. Available at: Incremental Value of CSF Biomarkers in Clinically Diagnosed AD and Non-AD Dementia - PMC (nih.gov). Accessed July 20, 2023.
  15. Anoop, A., Singh, P., et al. CSF Biomarkers for Alzeheimer’s Disease Diagnosis. Available at: CSF Biomarkers for Alzheimer's Disease Diagnosis - PMC (nih.gov). Accessed July 20, 2023
  16. McKhann GM, Knopman DS, Chertkow 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):263-269.
  17. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment 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):270-279.
  18. ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT02477800.
  19. ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT02484547.
  20. Aducanumab [unapproved dossier], Cambridge, MA: Biogen; 2020.
  21. 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;65(8):1091–1095.
  22. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-198.
  23. Sevigny, J., Chiao, P., Bussière, T. et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature 537, 50–56 (2016).
  24. Per clinical consult with neurologist, January 21, 2021.
  25. Aduhelm prescribing information. Biogen, Inc. Cambridge, MA. February 2023.
  26. Blennow K, Mattsson N, Scholl M, et al. Amyloid biomarkers in Alzheimer's disease. Trends Pharmacol Sci 2015;36:297–309.
  27. ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT01677572.
  28. ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT04241068.
  29. Wolk DA, Dickerson BC. Clinical features and diagnosis of Alzheimer disease. UpToDate Web site. http://www.uptodate.com. Accessed February 1, 2023.
  30. FDA accepts Biologics License Application for subcutaneous maintenance dosing of Leqembi® (lecanemab-irmb) in the US. Available at: https://www.bioarctic.com/en/fda-accepts-biologics-license-application-for-subcutaneous-maintenance-dosing-of-leqembi-lecanemab-irmb-in-the-us/. Accessed May 12, 2025.
  31. Meglio, M. Eisai Formally Submits BLA for Subcutaneous Autoinjector of Lecanemab. Available at: https://www.neurologylive.com/view/eisai-formally-submits-bla-subcutaneous-autoinjector-lecanemab. November 2024. Accessed May 12, 2025.
  32. Meglio, M. FDA Accepts BLA for Subcutaneous Autoinjector Formulation of Lecanemab. Available at: https://www.neurologylive.com/view/fda-accepts-bla-subcutaneous-autoinjector-formulation-lecanemab. January 2025. Accessed May 12, 2025.
  33. Eisai Presents New Leqembi (lecanemab-irmb) Investigational Subcutaneous Formulation Interim Study Results and Clinical Improvement Data in Earlier Stages of Early Alzheimer’s Disease From Additional Analyses of Clarity AD at The Clinical Trials On Alzhe. Available at: https://investors.biogen.com/news-releases/news-release-details/eisai-presents-new-leqembir-lecanemab-irmb-investigational. October 2023. Accessed May 12, 2025.
  1. In clinical trials, completion of active treatment was based on amyloid PET levels measured at week 24, week 52, and week 76. [1,7]
  2. In the TrailBlazer -ALZ 2 people were able to complete treatment and switch to placebo at 6, 12, or 18 months after they achieved one of the study’s treatment goals, minimal levels of amyloid plaque, consistent with a visually negative amyloid PET scan. In the overall population of people receiving Kisunla, 17% completed treatment at 6 months, 47% at 12 months, and 69% at 18 months based on assessment of amyloid levels via a amyloid PET scan. Kisunla dosing can be stopped based on reduction of amyloid plaques to minimal levels on amyloid PET imaging. Amyloid positron emission tomography (PET) levels were measured at weeks 24, 52, and 76. Amyloid PET values may increase after treatment with donanemab is stopped. [1]
  3. Core CSF biomarker assessment is defined as a combination of amyloid-β 1-42 peptide (Aβ42, which is correlated with APP metabolism and amyloid deposition), Total Tau protein (T-Tau) which reflects neurodegeneration, and phosphorylated Tau protein (P-Tau181) which reflects tangle pathology measurement. According to the literature, these core biomarkers have a high specificity and sensitivity for discriminating AD from other dementias The typical CSF biomarker profile in AD associates increased T-Tau and P-Tau181 concentrations and decreased Aβ42 peptide concentration. It has been clearly demonstrated that a combination of CSF biomarkers that includes Aβ42/Aβ40 ratio calculation, significantly improves the discriminatory capacity in the diagnosis of AD [6]
  4. The SC-AI 360 mg weekly maintenance Leqembi regimen will allow patients who have completed the biweekly intravenous (IV) initiation phase, exact period under discussion with the FDA, to receive weekly doses that are expected to maintain the clinical and biomarker benefits. The SC-AI is expected to be simple and easy for patients and their care partners to use, and may reduce the need for hospital or infusion site visits and nursing care for IV administration. [30]
  5. The SC dosage form of Leqembi, helps clear highly toxic protofibrils, which can still cause neuronal damage even after amyloid-beta (Aβ) plaque is cleared from the brain. The BLA for the subcutaneous formulation is based on data from the phase 3 Clarity AD trial (NCT03887455), the supportive trial that led to lecanemab’s approval, its open-label extension (OLE), and modeling of observed data. The data showed that after 6 months of treatment, those on the SC-AI demonstrated a 14% increased amyloid plaque removal than those who received IV administration. Pharmacokinetic data also demonstrated that 90% exposure for subcutaneous vs IV was within the bioequivalence limits of 80% to 125%, allowing Eisai to select a dose for future patients that achieve area under the curve that are comparable to the IV formulation dose. [31- 32]
  • 2025-09-04: Update guideline
  • 2024-08-01: update guideline
  • 2024-04-24: 2024 Annual Review
  • 2023-05-03: Annual review - updated references.
  • 2023-03-31: Updated GPIs
  • 2023-02-16: Add submission of medical records where applicable, criterion to not to be used in combination with other mAbs for AD, and clarified follow-up MRI requirements. Added criterion regarding ApoE e4 testing. Added additional blood testing option. Updated references.
  • 2022-06-01: Remove submission of records from ORx standard
  • 2022-04-25: Annual Review
  • 2021-06-24: Program Update
  • 2021-06-16: Program Update