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ALZHEIMER'S DISEASE (AD) MAY BE LINKED TO A PROTEIN IN THE BRAIN CALLED AMYLOID1-2

Once symptoms present, significant levels of amyloid have already built up1-2

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AD may be linked to a buildup of amyloid plaques in the brain – starting about 20 years before symptoms appear1-2

Amyloid icon

Amyloid is a protein that the body produces naturally, but an excessive buildup of amyloid plaques in the brain may be associated with memory and thinking issues1-2

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When combined with clinical assessments, blood-based biomarker (BBM) assays can help identify AD pathology and aid in the diagnosis of patients with early symptomatic AD3*

*For patients being evaluated for AD and other causes of cognitive impairment, blood-based biomarker tests interpreted in conjunction with clinical assessment can be used to detect or rule out evidence of AD pathology, including amyloid.4

BLOOD BIOMARKER TESTS SUCH AS P-TAU217 CAN HELP FACILITATE EARLY DETECTION OF AD PATHOLOGY3

95%

of surveyed US adults said they would want a simple medical test to detect biomarkers associated with Alzheimer’s disease pathology, should they experience early symptoms6

5x

MORE LIKELY

Patients with MCI and amyloid positivity are 5x more likely to experience clinical progression in the natural course of the disease compared to those who are not amyloid positive7

90%

ACCURACY

Many blood tests that include P-tau217 demonstrate accuracy of approximately 90% similar to FDA-approved/cleared CSF IVD tests, and are concordant with amyloid PET status and align to the highest standard of CEOi guidance3,4,9-12

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BBMs offer a fast, less invasive, and cost-effective method to aid in the early detection and diagnosis of AD pathology in symptomatic patients8

Commercially available BBM tests used to detect amyloid positivity are not standalone tests. The results must be interpreted in conjunction with clinical assessment results. Patients must meet testing criteria.4

PET scans and CSF tests are also available to help assess amyloid pathology in patients with suspected AD, and there are additional AD biomarkers beyond P-tau217 that could be considered in a diagnostic workup.4

The Global CEOi BBM Workgroup is a partnership consisting of individuals in academia who help validate blood-based biomarker tests and diagnostics, the medical device companies that develop them, pharmaceutical companies developing treatment pathways where BBMs may be useful, and patient advocacy groups that aim to improve AD care and treatment. Together, CEOi works to address major challenges in the field of AD and the BBM workgroup was established to examine the minimum acceptable performance standards of BBM tests in clinical use.4

Learn about commercially available blood tests
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Things to Know about BBMs:

BBM Perception:

BBMs just add another step in the assessment process and don't help in the referral.

The Things to Know:

BBMs are low-cost, scalable, and globally accessible. These tests may help ensure patients are triaged to the right specialists based on results, directing patients that present with amyloid pathology to appropriate care while reducing unnecessary referrals of patients without AD.4,12,13

BBM Perception:

Primary care providers need highly specialized symptomatic AD training to order or interpret BBMs.

The Things to Know:

BBM tests are accessible and can be ordered through major laboratories.

Additionally, interpretation guidance and algorithms can be integrated into care workflows for continuing patient assessment.4,13

BBM Perception:

BBMs results are difficult to speak to patients about.

The Things to Know:

Doctors can reassure patients that an indeterminate or positive result simply advances their need to see a specialist and have a more complete assessment.

These results are not a confirmation of an AD diagnosis alone. Test results can help rule out or facilitate a diagnosis and timely treatment for patients at the earliest symptomatic stages of disease.4,9,13-16

BBM Perception:

Adding BBM tests will drive up testing costs and may feel out of reach for some patients.

The Things to Know:

Based on CEOi guidance, using plasma P-tau217 in conjunction with clinical assessments can result in cost savings of up to 60% compared to CSF tests and 81% compared to PET scans, making them cost effective.4,5,13

*The multidisciplinary BBM Workgroup convened by the Global CEOi on Alzheimer’s disease developed appropriate use recommendations for using blood biomarkers in AD pathology detection in the diagnostic process

The Global CEOi BBM Workgroup is a partnership consisting of individuals in academia who help validate blood-based biomarker tests and diagnostics, the medical device companies that develop them, pharmaceutical companies developing treatment pathways where blood-based biomarkers may be useful, and patient advocacy groups that aim to improve AD care and treatment. Together, CEOi works to address major challenges in the field of AD, and the BBM Workgroup was established to examine the minimum acceptable performance standards of blood-based biomarker tests in clinical use.

AD=Alzheimer’s disease; BBM=blood-based biomarker; CEOi=Global CEO Initiative on Alzheimer’s disease; CSF=cerebrospinal fluid; PET=positron emission tomography; P-tau=phosphorylated tau.

References:

  1. Porsteinsson AP, Isaacson RS, Knox S, et al. Diagnosis of early Alzheimer’s disease: clinical practice in 2021. J Prev Alzheimers Dis. 2021;8:371-386.
  2. Alzheimer’s Association. 2024 Alzheimer’s disease facts and figures. Alzheimers Dement. 2024;20(5):3708-3821. doi:10.1002/alz.13809
  3. Palmqvist S, Tideman P, Mattsson-Carlgren N, et al. Blood biomarkers to detect Alzheimer disease in primary care and secondary care. JAMA. 2024;332(15):1245-1257.
  4. Schindler SE, Galasko D, Pereira AC, et al. Acceptable performance of blood biomarker tests of amyloid pathology — recommendations from the Global CEO Initiative on Alzheimer’s Disease. Nat Rev Neurol. 2024;20(7):426-439.
  5. Palmqvist S, Warmenhoven N, Anastasi F, et al. Plasma phospho-tau217 for Alzheimer’s disease diagnosis in primary and secondary care using a fully automated platform. Nat Med. 2025;31(6):2036-2043. doi:10.1038/s41591-025-03622-w
  6. Alzheimer's Association. 2025 Alzheimer's disease facts and figures. Alzheimers Dement. 2025;21(4):e70235. doi:10.1002/alz.70235
  7. Huszár Z, Engh MA, Pavlekovics M, et al. Risk of conversion to mild cognitive impairment or dementia among subjects with amyloid and tau pathology: a systematic review and meta-analysis. Alzheimers Res Ther. 2024;16(81):1-19. https://doi.org/10.1186/s13195-024-01455-2
  8. Hampel H, O’Bryant SE, Molinuevo JL, et al. Blood-based biomarkers for Alzheimer’s disease: mapping the road to the clinic. Nat Rev Neurol. 2018;14(11):639-652.
  9. Hansson O, Edelmayer RM, Boxer AL, et al. The Alzheimer’s Association appropriate use recommendations for blood biomarkers in Alzheimer’s disease. Alzheimers Dement. 2022;18(12):2669-2686. doi:10.1002/alz.12756
  10. Ashton NJ, Brum WS, Di Molfetta G, et al. Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer disease pathology. JAMA Neurol. 2024;81(3):255-263. doi:10.1001/jamaneurol.2023.5319
  11. Schindler SE, Petersen KK, Saef B, et al; Alzheimer’s Disease Neuroimaging Initiative (ADNI) Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium Plasma Aβ and Phosphorylated Tau as Predictors of Amyloid and Tau Positivity in Alzheimer’s Disease Project Team. Head-to-head comparison of leading blood tests for Alzheimer’s disease pathology. Alzheimers Dement. 2024;20(11):8074-8096. doi:10.1002/alz.14315
  12. Palmqvist S, Whitson HE, Allen LA, et al. Alzheimer's Association Clinical Practice Guideline 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(7):1-127. doi:10.1002/alz.70535
  13. Hampel H, Au R, Mattke S, et al. Designing the next-generation clinical care pathway for Alzheimer’s disease. Nat Aging. 2022;2(8):692-703. doi:10.1038/s43587-022-00269-x
  14. Jack CR Jr, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimers Dement. 2024;20(8):5143-5169. doi:10.1002/alz.13859
  15. Mattsson-Carlgren N, Janelidze S, Bateman RJ, et al. Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau. EMBO Mol Med. Published online May 5, 2021. doi:10.15252/emmm.202114022
  16. Hazan J, Liu KY, Fox N, et al. Advancing diagnostic certainty in Alzheimer’s disease: a synthesis of the diagnostic process. J Alzheimers Dis. 2023;94(2):473-482. doi:10.3233/JAD-230186

IMPORTANT SAFETY INFORMATION FOR Kisunla® (donanemab-azbt)

WARNING: AMYLOID-RELATED IMAGING ABNORMALITIES

Monoclonal antibodies directed against aggregated forms of beta amyloid, including Kisunla, can cause amyloid-related imaging abnormalities (ARIA), characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events can occur. ARIA can be fatal. Serious intracerebral hemorrhages >1 cm, some of which have been fatal, have been observed in patients treated with this class of medications. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, treating clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy in a patient being treated with Kisunla.

ApoE ε4 Homozygotes: Patients treated with this class of medications, including Kisunla, who are apolipoprotein E ε4 (ApoE ε4) homozygotes (approximately 15% of Alzheimer’s disease patients) have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, the risk of ARIA across genotypes and the implications of genetic testing results should be discussed with patients.

Consider the benefit for treating Alzheimer's disease and risk of ARIA when deciding to treat with Kisunla.

Kisunla is contraindicated in patients with known serious hypersensitivity to donanemab-azbt or to any of the excipients. Reactions have included anaphylaxis.

Amyloid-Related Imaging Abnormalities (ARIA)

ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, can occur. ARIA can be fatal. When present, reported symptoms associated with ARIA may include, but are not limited to, headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve over time.

In Study 1, safety was assessed in patients who received Kisunla Dosing Regimen 1 (n=853) compared to those who received placebo (n=874). In Study 2, the effect of different dosing regimens of Kisunla on ARIA was assessed, including in patients who received Kisunla Dosing Regimen 2 (n=212).

Incidence of ARIA

A lower incidence of ARIA was observed with Dosing Regimen 2 as compared to Dosing Regimen 1. Therefore, Dosing Regimen 2 is the recommended dosage for Kisunla.

In Study 1, symptomatic ARIA-E occurred in 6% of patients through 18 months of treatment with Kisunla.

Clinical symptoms associated with ARIA resolved in approximately 85% of those patients.

Including asymptomatic radiographic events, ARIA, ARIA-E, and ARIA-H were observed with Kisunla: 36%, 24%, and 31% of patients treated with Kisunla, respectively compared to 14%, 2%, and 13% of patients on placebo. There was no increase in isolated ARIA-H for Kisunla vs placebo.

In Study 2, symptomatic ARIA-E occurred in 3% of patients and symptomatic ARIA-H occurred in less than 1% of patients through 12 months of treatment with Kisunla. Clinical symptoms associated with ARIA-E resolved in approximately 67% of patients at 12 months. Including asymptomatic radiographic events, ARIA, ARIA-E, and ARIA-H were observed in 29%, 16%, and 25% of patients treated with Kisunla.

Incidence of Intracerebral Hemorrhage (ICH)

ICH >1 cm in diameter was reported in 0.5% of patients treated with Kisunla vs 0.2% on placebo in Study 1 and in 1% of patients treated with Kisunla in Study 2. Fatal events of ICH have been observed in patients taking Kisunla.

Risk Factors for ARIA and ICH

ApoE ε4 Carrier Status

The risk of ARIA, including symptomatic and serious ARIA, is increased in ApoE ε4 homozygotes.

Recommendations for management of ARIA do not differ based on ApoE ε4 carrier status. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. An FDA-authorized test for detection of ApoE ε4 alleles is not currently available. Currently available tests may vary in accuracy and design.

Radiographic Findings of Cerebral Amyloid Angiopathy (CAA)

Neuroimaging findings that may indicate CAA include evidence of prior ICH, cerebral microhemorrhage, and cortical superficial siderosis. CAA has an increased risk for ICH. The presence of an ApoE ε4 allele is also associated with CAA.

The baseline presence of at least 2 microhemorrhages or the presence of at least 1 area of superficial siderosis on magnetic resonance imaging (MRI), which may be suggestive of CAA, were identified as risk factors for ARIA. Patients were excluded from enrollment in Study 1 and Study 2 for findings on neuroimaging of prior ICH >1 cm in diameter, >4 microhemorrhages, >1 area of superficial siderosis, severe white matter disease, and vasogenic edema.

Concomitant Antithrombotic or Thrombolytic Medication

In Study 1, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed. The majority of exposures to antithrombotic medications were to aspirin. The number of events and the limited exposure to non-aspirin antithrombotic medications limit definitive conclusions about the risk of ARIA or ICH in patients taking antithrombotic medications.

One fatal ICH occurred in a patient taking Kisunla in the setting of focal neurologic symptoms of ARIA and the use of a thrombolytic agent in Study 1, and one fatal intracerebral hemorrhage occurred in the setting of ARIA and the use of a thrombolytic agent in Study 2. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, treating clinicians should consider whether such symptoms could be due to ARIA-E, and additional caution should be exercised when considering the administration of antithrombotics or a thrombolytic agent (eg, tissue plasminogen activator) to a patient being treated with Kisunla. Advise patients to carry information that they are being treated with Kisunla.

Caution should be exercised when considering the use of Kisunla in patients with factors that indicate an increased risk for ICH and in particular for patients who need to be on anticoagulant therapy or patients with findings on MRI that are suggestive of CAA.

Monitoring and Dose Management Guidelines

Obtain a recent baseline brain MRI prior to initiating treatment and prior to the 2nd, 3rd, 4th, and 7th infusions. Enhanced clinical vigilance for ARIA is recommended during the first 24 weeks of treatment with Kisunla. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment.

Recommendations for dosing in patients with ARIA-E and ARIA-H depend on clinical symptoms and radiographic severity. Depending on ARIA severity, use clinical judgment in considering whether to continue dosing, interrupt treatment, or permanently discontinue Kisunla. See Prescribing Information for additional dosing considerations.

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis and angioedema, have occurred in patients who were treated with Kisunla. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction and initiate appropriate therapy.

Infusion-Related Reactions (IRR)

IRRs were observed with Kisunla with the majority occurring within the first 4 infusions. Most IRRs occurred during the infusion or within 30 minutes after completion of the infusion, however some have occurred hours after an infusion. Signs and symptoms of IRRs include chills, erythema, nausea/vomiting, flushing, difficulty breathing/dyspnea, sweating, elevated blood pressure, headache, chest pain, and low blood pressure.

In the event of an IRR, the infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Consider pre-treatment with antihistamines, acetaminophen, or corticosteroids prior to subsequent dosing.

Adverse Reactions: The most common adverse reactions reported in ≥5% of patients treated with Kisunla and ≥2% higher than placebo were ARIA-H microhemorrhage, ARIA-E, ARIA-H superficial siderosis, headache, and IRRs.

Kisunla (donanemab-azbt) injection for intravenous use is available as a 350 mg/20 mL single-dose vial.

Please see full Prescribing Information, including Boxed Warning regarding ARIA, and Medication Guide.

DN HCP ISI 01JUL2025

INDICATION

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.