If you wish to report an adverse event or product complaint, please call 1-800-LILLYRX (1-800-545-5979)
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.
What were the adverse reactions reported in Kisunla™ (donanemab-azbt) clinical trials?
The most common adverse reactions in donanemab-treated participants in TRAILBLAZER-ALZ 2 and TRAILBLAZER-ALZ 6 were amyloid-related imaging abnormalities, headache, and infusion-related reactions. Most events were mild or moderate in severity.
See important safety information, including boxed warning, in the attached prescribing information.
TRAILBLAZER-ALZ 2 Trial
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 Alzheimer's disease (AD).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
Baseline demographics were similar between donanemab and placebo treatment groups. The 853 donanemab-treated participants were mostly female (57%) and white (91%), with a mean age of 73 years at study entry (range 59 to 86 years).1,3
In TRAILBLAZER-ALZ 2,
Adverse reactions of donanemab were determined from the TEAE preferred terms reported in the study. Events were determined to be adverse reactions based on the strength of the association with donanemab treatment assessed using
- predefined statistical criteria
- biological plausibility for a donanemab effect
- clinical importance, and
- medical judgment.4
Adverse Reactions of Donanemab
The most frequently reported adverse reactions by donanemab-treated participants in TRAILBLAZER-ALZ 2 were
- amyloid-related imaging abnormalities (ARIA)
- headache, and
- infusion-related reactions (Adverse Reactions Reported by ≥5% of Donanemab-Treated Participants and ≥2% Higher Than Placebo in TRAILBLAZER-ALZ 2).3
Placebo |
Donanemab |
|
ARIA-H microhemorrhagec |
11 |
25 |
ARIA-Ed |
2 |
24 |
ARIA-H superficial siderosisc |
3 |
15 |
Headache |
10 |
13 |
Infusion-related reaction |
0.5 |
9 |
Abbreviations: ARIA-E = amyloid-related imaging abnormalities-edema observed on MRI as vasogenic cerebral edema or sulcal effusions; ARIA-H = amyloid-related imaging abnormalities-hemosiderin deposition which includes superficial siderosis and microhemorrhage; MedDRA = Medical Dictionary for Regulatory Activities; MRI = magnetic resonance imaging; TEAE = treatment-emergent adverse event.
aMedDRA version 25.1.
bThis analysis set includes participant data from the first dose of treatment to the last dose plus 57 days.
cAs assessed by MRI. A participant could have both microhemorrhage and superficial siderosis.
dAs assessed by MRI or TEAE cluster.
The Appendix provides additional information on ARIA, including a description of the events and symptoms.
More information about the characterization of ARIA and infusion-related reactions in donanemab clinical trials is available here: ARIA, infusion-related reactions.
Serious Adverse Events
A serious adverse event (SAE) is defined as any event or reaction that
- results in death
- is life-threatening
- requires in-patient hospitalization or prolongation of existing hospitalization
- results in persistent or significant incapacity or disability
- is a congenital anomaly or birth defect, or
- is a medically important event or reaction "for other reasons serious."4
The frequency of SAEs was similar between treatment groups in TRAILBLAZER-ALZ 2.1 Serious Adverse Events Occurring in ≥1% of Donanemab-Treated Participants: TRAILBLAZER-ALZ 2 shows SAEs that occurred in ≥1% of donanemab-treated participants while on treatment.
Preferred Term |
Placebo |
Donanemab |
Deathsa |
10 (1.1) |
16 (1.9) |
Participants ≥1 SAE |
138 (15.8) |
148 (17.4) |
Syncope |
13 (1.5) |
9 (1.1) |
ARIA-E |
0 (0.0) |
13 (1.5) |
COVID-19 |
4 (0.5) |
9 (1.1) |
Abbreviations: ARIA-E: amyloid-related imaging abnormalities-edema observed on MRI as vasogenic cerebral edema or sulcal effusions; COVID-19 = coronavirus disease 19; MRI = magnetic resonance imaging; SAE = serious adverse event.
aDeaths are also included as SAEs.
Deaths
In the TRAILBLAZER-ALZ 2 study, deaths were reported in participants receiving
- placebo (n=10, 1.1%), and
- donanemab (n=16, 1.9%).1
A total of 3 participants in the donanemab treatment group reported serious ARIA and subsequently died. These deaths were attributed to
- amyloid-related imaging abnormalities-edema (ARIA-E, n=1)
- amyloid-related imaging abnormalities-hemosiderin deposition (ARIA-H, n=1), and
- concurrent ARIA-E and ARIA-H (n=1).1
Discontinuations Due to Adverse Events
Discontinuations from study treatment due to adverse events were higher in the donanemab treatment group compared with the placebo group: Adverse Events Leading to Treatment Discontinuation in ≥0.5% of Donanemab Participants: TRAILBLAZER-ALZ 2.1,3
The most common adverse event leading to discontinuation of donanemab was infusion-related reaction (4%) compared to none on placebo.3
Preferred Term |
Placebo |
Donanemab |
Participants with treatment discontinuation due to AEs |
38 (4.3) |
112 (13.1) |
Infusion-related reaction |
0 (0.0) |
31 (3.6) |
ARIA-E |
3 (0.3) |
21 (2.5) |
ARIA-H |
2 (0.2) |
7 (0.8) |
Hypersensitivity |
0 (0.0) |
4 (0.5) |
Abbreviations: AE = adverse event; ARIA-E = amyloid-related imaging abnormalities-edema observed on MRI as vasogenic cerebral edema or sulcal effusions; ARIA-H = amyloid-related imaging abnormalities-hemosiderin deposition; MRI = magnetic resonance imaging.
TRAILBLAZER-ALZ 2 Long-Term Extension
Participants who completed the placebo-controlled period of the TRAILBLAZER-ALZ 2 study were eligible to enter a 78-week double-blind long-term extension. Early start participants were those initially randomized to donanemab in the placebo-controlled period. Delayed start participants were those initially randomized to placebo in the placebo-controlled period and started donanemab in the long-term extension. Participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were selected as external control.5
No new safety signals were observed in the long-term extension study versus the established safety profile.5
TRAILBLAZER-ALZ 6 Trial
The TRAILBLAZER-ALZ 6 study investigated the impact of different donanemab dosing options on the frequency of ARIA-E in relation to amyloid reduction. All participants received a dosing regimen that includes donanemab, but at different dose levels and frequency of dosing. The modified titration regimen met the primary objective of >80% probability of achieving ≥20% reduction in relative risk of developing ARIA-E compared with the dosing regimen used in the TRAILBLAZER-ALZ 2 study (referred to as standard dosing in the TRAILBLAZER-ALZ 6 study).6 Therefore, the modified titration regimen is the recommended dosage for donanemab.3
In the modified titration regimen, participants received intravenous donanemab doses every 4 weeks as follows:
- 350 mg for infusion 1
- 700 mg for infusion 2
- 1050 mg for infusion 3, and
- 1400 mg for infusion 4 and beyond.6
Safety Overview
At 76 weeks, the frequency of SAEs was 24.6% in the standard dosing and 23.1% in the modified titration arm. The rates of TEAEs were similar between the standard and modified titration arms (Safety Overview Through Week 76 in TRAILBLAZER-ALZ 6).6
Categorya |
Standard |
Modified Titration |
1 (0.5) |
1 (0.5)d |
|
SAEs |
51 (24.6) |
49 (23.1) |
Discontinuations from study due to AEs |
6 (2.9) |
6 (2.8) |
Discontinuations from treatment due to AEs |
16 (7.7) |
17 (8.0) |
TEAEs |
191 (92.3) |
199 (93.9) |
TEAEs related to study treatmente |
110 (53.1) |
114 (53.8) |
Abbreviations: AE = adverse event; SAE = serious adverse event; TEAE = treatment-related adverse event.
aParticipants may be counted in more than one category
bDeaths are also included as SAEs and discontinuations due to AEs.
cPreferred term for cause of death: cardio-respiratory arrest (standard arm); cerebral haemorrhage (modified titration arm)
dDeath due to cerebral hemorrhage following thrombolytic administration for presumed acute right middle cerebral artery stroke.
eIncludes events that were considered related to study treatment as judged by the investigator.
Compared with rates reported in the standard arm, participants in the modified titration arm in TRAILABLAZER-ALZ 6 reported
- higher rates of hypersensitivity reactions and infusion-related reactions and
- a lower rate of ARIA-E.3
Treatment-emergent adverse reactions reported in more than 15% of participants in the modified titration arm (vs the standard arm) in TRAILBLAZER-ALZ 6 were
- headache (20.3% vs 24.2%)
- fall (19.8% vs 14.0%)
- ARIA-H (18.4% vs 19.8%)
- COVID-19 (17.9% vs 12.6%)
- infusion-related reaction (17.9% vs 14.0%), and
- ARIA-E (15.6% vs 24.2%).6
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
2Solomon PR. TRAILBLAZER-ALZ 2: clinical background and study design. Abstract presented at: Alzheimer's Association International Conference (AAIC); July 16-20, 2023; Amsterdam, Netherlands.
3Kisunla [package insert]. Indianapolis, IN: Eli Lilly and Company; 2025.
4Data on file, Eli Lilly and Company and/or one of its subsidiaries.
5Sims JR. Donanemab in early symptomatic Alzheimer’s disease: efficacy and safety from the TRAILBLAZER‐ALZ 2 long-term extension. Presented as an oral presentation at: Alzheimer's Association International Conference (AAIC); July 27-31, 2025; Toronto, Canada.
6Wang H, Nery ESM, Ardayfio P, et al. The effect of modified donanemab titration on amyloid-related imaging abnormalities with edema/effusions and amyloid reduction: 18-month results from TRAILBLAZER-ALZ 6. J Prev Alzheimers Dis. Published online July 5, 2025. https://doi.org/10.1016/j.tjpad.2025.100266
7Wang H, Nery ESM, Ardayfio P, et al. Modified titration of donanemab reduces ARIA risk and maintains amyloid reduction. Alzheimers Dement. 2025;21(4):e70062. https://doi.org/10.1002/alz.70062
8Sperling RA, Jack Jr CR, Black SE, et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimers Dement. 2011;7(4):367-385. https://doi.org/10.1016/j.jalz.2011.05.2351
9Cogswell PM, Barakos JA, Barkhof F, et al. Amyloid-related imaging abnormalities with emerging Alzheimer disease therapeutics: detection and reporting recommendations for clinical practice. AJNR Am J Neuroradiol. 2022;43(9):E19-E35. https://doi.org/10.3174/ajnr.A7586
10Ketter N, Brashear HR, Bogert J, et al. Central review of amyloid-related imaging abnormalities in two phase III clinical trials of bapineuzumab in mild-to-moderate Alzheimer’s disease patients. J Alzheimers Dis. 2017;57(2):557-573. https://doi.org/10.3233/JAD-160216
Appendix
Amyloid-Related Imaging Abnormalities Overview
Amyloid-related imaging abnormalities can be detected by brain magnetic resonance imaging (MRI) and have been observed in clinical trials of monoclonal antibodies directed against aggregated forms of beta amyloid.3,8 The 2 forms of ARIA are
- ARIA-E, observed on MRI as vasogenic cerebral edema or sulcal effusions, and
- ARIA-H, which includes microhemorrhage and superficial siderosis.3,8,9
These are typically detected on different MRI sequences and are thought to share common underlying pathological mechanisms.8,9
Amyloid-related imaging abnormalities are 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.3
Also known as vasogenic edema, the mechanism of ARIA-E is thought to be a function of increased permeability of brain capillary endothelial cells to serum proteins resulting in increased extracellular fluid volume. It is generally
In ARIA-H, hemosiderin deposits are present on MRI, including
Date of Last Review: July 15, 2025