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Kisunla ™ (donanemab-azbt) injection, for intravenous infusion
350 mg/20 mL (17.5 mg/mL)
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
How should response to Kisunla™ (donanemab-azbt) treatment be monitored for efficacy?
Dosing was continued or stopped in response to observed effects on amyloid imaging in TRAILBLAZER-ALZ 2. The percentages of participants eligible for a dose reduction to placebo were 17% at week 24, 47% at week 52, and 69% at week 76.
See important safety information, including boxed warning, in the attached prescribing information.
Patient Monitoring for Disease Progression
Treatment with donanemab has been shown to slow the progression of Alzheimer's disease (AD), but it does not halt disease progression.1
Donanemab is indicated for the treatment of AD. Treatment with donanemab should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease.2
Consider stopping dosing with donanemab based on reduction of amyloid plaques to minimal levels on amyloid PET imaging.2 Clinical judgment should be used when considering whether an individual patient’s dosing should be continued or stopped in the absence of a safety issue. Clinical judgment may be informed by factors such as clinical assessments conducted at regular intervals and amyloid beta pathology.
TRAILBLAZER-ALZ 2 Trial of Donanemab in Early Symptomatic Alzheimer's Disease
A phase 3, placebo-controlled 72-week study evaluated the safety and efficacy of donanemab in adults aged 60 to 85 years with early symptomatic AD.1
Eligible participants had
- a Mini-Mental State Examination (MMSE) score of 20 to 28 (scores range from 0 to 30, with higher scores indicating better mental performance), and
- presence of amyloid pathology assessed by amyloid positron emission tomography (PET) imaging (≥37 centiloids [CL]) with either florbetapir F 18 or florbetaben F 18, and tau pathology assessed by flortaucipir F 18 PET imaging.1
Participants were randomized at the beginning of double-blind treatment in a 1:1 ratio to receive intravenous infusions every 4 weeks of either
Completion of active treatment in the clinical trial was guided by amyloid PET levels measured at week 24 and week 52. Participants were eligible to be switched to placebo if the amyloid plaque level was
- <11 CL on a single PET scan, or
- 11 to <25 CL on 2 consecutive PET scans.1
Evaluating Changes in MMSE
In the TRAILBLAZER-ALZ 2 study, mean MMSE scores at baseline were
- 22.4 in donanemab-treated participants, and
- 22.2 in participants receiving placebo.1
At week 76, donanemab-treated participants had statistically significantly less decline on the MMSE score (-2.47; p<.01 vs placebo) than participants receiving placebo (-2.94); the mean MMSE scores at week 76 were
- 20.7 in donanemab-treated participants (p<.01 vs placebo), and
- 19.8 in participants receiving placebo.1
Evaluating Changes in Amyloid Positron Emission Tomography
Dosing was continued or stopped in response to observed effects on amyloid imaging in the TRAILBLAZER-ALZ 2 study. The percentages of donanemab-treated participants who were eligible to be switched to placebo based on amyloid PET levels were
The percentage of participants with amyloid reduction to minimal levels (defined as <24.1 CL on amyloid PET, consistent with a visually negative read) was also measured in the study.1
The percentages of donanemab-treated participants who met this threshold on amyloid PET were
- 30% at week 24
- 66% at week 52, and
- 76% at week 76.1
Evaluating Changes in Plasma P-tau217
The treatment effect of donanemab on changes in plasma phosphorylated-tau 217 (P-tau217) at week 76 was also evaluated as an exploratory outcome.1
Although a reduction in plasma P-tau217 was observed with donanemab compared to placebo (Change From Baseline in Plasma P-tau217 at Week 76 in TRAILBLAZER-ALZ 2),1,2 the use of blood biomarkers has not been established for therapeutic monitoring of therapy with amyloid-targeting therapies.4
|
Combined Population |
|
Donanemab |
Placebo |
|
Mean baseline |
0.67 |
0.66 |
Change from baseline (% of original value) |
-0.19 (-35.0%) |
0.03 |
Difference from placebo |
-0.22b |
NA |
Abbreviations: MMRM = mixed model for repeated measures; NA = not applicable; P-tau217 = tau phosphorylated at threonine 217.
aChange from baseline and p-value are derived using MMRM methodology with fixed factors for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, and age at baseline.
bp<.0001 vs placebo.
An analysis of the TRAILBLAZER-ALZ 2 study found a positive correlation between early amyloid change and early plasma P-tau217 changes. However, plasma biomarker changes have limited ability to predict amyloid reduction to minimal levels at this time.6
Evaluating Amyloid Plaque Reduction Via CSF or Other Fluid Biomarkers
The use of cerebrospinal fluid (CSF) and other fluid biomarkers have been shown to be helpful in distinguishing AD from non-AD neurodegenerative disorders. However, measuring amyloid plaque reduction during treatment with an amyloid-targeting therapy via CSF or other fluid biomarkers in everyday clinical practice requires further high-quality studies.7-10
Imaging biomarkers demonstrate insoluble aggregates (eg, amyloid plaque) and represent a cumulative effect. Fluid biomarkers indicate the balance of production and clearance rates of analytes at a specific moment.11 No concordance data support using CSF or other fluid biomarkers as substitutes for amyloid PET for therapeutic monitoring.
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Sims JR, Zimmer JA, Evans CD, et al; TRAILBLAZER-ALZ 2 Investigators. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA. 2023;330(6):512-527. https://doi.org/10.1001/jama.2023.13239
2Kisunla [package insert]. Indianapolis, IN: Eli Lilly and Company; 2025.
3Solomon PR. TRAILBLAZER-ALZ 2: clinical background and study design. Abstract presented at: Alzheimer's Association International Conference (AAIC); July 16-20, 2023; Amsterdam, Netherlands.
4Hansson 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. https://doi.org/10.1002/alz.12756
5Data on file, Eli Lilly and Company and/or one of its subsidiaries.
6Mintun M. Advances in our understanding of amyloid plaque-clearing therapies. Presented at: 18th International Conference on Alzheimer's Disease and Parkinson's Disease (ADPD). March 5-9, 2024
7Salvadó G, Ossenkoppele R, Ashton NJ, et al. Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads. EMBO Mol Med. 2023;15(5):e17123. https://doi.org/10.15252/emmm.202217123
8Niemantsverdriet E, Valckx S, Bjerke M, Engelborghs S. Alzheimer's disease CSF biomarkers: clinical indications and rational use. Acta Neurol Belg. 2017;117(3):591-602. https://doi.org/10.1007/s13760-017-0816-5
9Iaccarino L, Burnham SC, Dell'Agnello G, et al. Diagnostic biomarkers of amyloid and tau pathology in Alzheimer's disease: an overview of tests for clinical practice in the United States and Europe. J Prev Alzheimers Dis. 2023;10(3):426-442. https://doi.org/10.14283/jpad.2023.43
10Angioni D, Delrieu J, Hansson O, et al. Blood biomarkers from research use to clinical practice: what must be done? A report from the EU/US CTAD task force. J Prev Alz Dis. 2022;9(4):569-579. http://dx.doi.org/10.14283/jpad.2022.85
11Jack 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. https://doi.org/10.1002/alz.13859
Date of Last Review: July 18, 2025