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 is the onset of ARIA in patients treated with Kisunla® (donanemab-azbt)?
The majority of first ARIA-E events occurred early in treatment (within 24 weeks of initiation of treatment), although ARIA can occur at any time and patients can have more than 1 episode.
See important safety information, including boxed warning, in the attached prescribing information.
Content Overview
- First Onset of ARIA in The Integrated Safety Analysis Sets
- First Onset of ARIA in TRAILBLAZER-ALZ 6
- References
- Appendix
First Onset of ARIA in The Integrated Safety Analysis Sets
The integrated safety analysis sets refer to two analysis sets, made up of
- the placebo-controlled analysis set, which includes data pooled from the double-blind, placebo-controlled portion of the phase 2 TRAILBLAZER-ALZ and phase 3 TRAILBLAZER-ALZ 2 studies, and
- the all donanemab analysis set which included 2727 participants with Alzheimer's disease who received at least 1 dose of donanemab in completed and ongoing phase 2 and phase 3 donanemab studies (includes participants entering the TRAILBLAZER-ALZ 2 long-term extension), not including participants in the TRAILBLAZER-ALZ 6 study.1
The studies included in the integrated safety analysis sets used a dosing regimen of 700 mg every 4 weeks for the first 3 doses, and then 1,400 mg every 4 weeks.2,3 This dose differs from the recommended dose (as described in the section entitled First Onset of ARIA in TRAILBLAZER-ALZ 6).
ARIA-E Onset
The majority of first amyloid-related imaging abnormalities-edema (ARIA-E) events occurred early in treatment (within the first 24 weeks), although amyloid-related imaging abnormalities (ARIA) can occur at any time and patients can have more than 1 episode.4
In the placebo-controlled analysis set, 24.4% of donanemab-treated participants compared to 1.9% of placebo-treated participants experienced ARIA-E. Events of ARIA-E can occur following the first infusion. In donanemab-treated participants who reported ARIA-E,
- nearly 88% experienced their first ARIA-E event by 24 weeks (Figure 1), and
- 80% of serious ARIA-E events occurred by the third donanemab infusion (Figure 2).1
Figure 1. Timing of First ARIA-E Occurrence Based on Safety MRI: Placebo-Controlled Treatment1
Figure 1 description: In the placebo-controlled studies, nearly 88% of donanemab-treated participants with ARIA-E had their first ARIA-E event by week 24. Magnetic resonance imaging studies were scheduled at weeks 4, 12, 24, 52, and 76.
Abbreviations: ARIA-E = amyloid-related imaging abnormalities-edema; MRI = magnetic resonance imaging.
ARIA-E: observed on MRI as vasogenic cerebral edema or sulcal effusion.
Figure 2. Timing of First Serious ARIA-E Event by Donanemab Infusion Number Based on MRI: Placebo-Controlled Treatment1
Figure 2 description: In the placebo-controlled studies, 80% of serious ARIA-E events occurred by the third infusion in donanemab-treated participants. No serious ARIA-E events were reported in the placebo group.
Abbreviations: ARIA-E = amyloid-related imaging abnormalities-edema; MRI = magnetic resonance imaging.
Note: A serious adverse event is as defined in the Appendix.
Please see the Appendix for a definition of serious adverse event.
In the larger all donanemab analysis set
- 89.6% of participants experienced their first ARIA-E event by 24 weeks, and
- 100% of serious ARIA-E events occurred by the sixth donanemab infusion.1
ARIA-H Onset
The incidence of amyloid-related imaging abnormalities-hemosiderin deposition (ARIA-H) during placebo-controlled treatment was
- 31.3% in donanemab-treated participants, and
- 13% in placebo-treated participants.1
In the placebo-controlled analysis set, 64.8% of first ARIA-H events occurred within the first 24 weeks of treatment (Figure 3). Of the 4 serious ARIA-H events, cumulatively, 75% of first serious ARIA-H events occurred before the fourth donanemab infusion.1
In the larger all donanemab analysis set, 71.7% of first ARIA-H events occurred within the first 24 weeks of treatment. Of the 9 serious ARIA-H events, cumulatively, 88.9% occurred before the seventh donanemab infusion.1
Figure 3. Timing of First ARIA-H Occurrence Based on Safety MRI: Placebo-Controlled Treatment1
Figure 3 description: In the placebo-controlled studies, 64.8% of first ARIA-H events occurred within the first 24 weeks of treatment. Magnetic resonance imaging studies were scheduled at weeks 4, 12, 24, 52, and 76.
Abbreviations: ARIA-H = amyloid-related imaging abnormalities-hemosiderin deposition; MRI = magnetic resonance imaging.
ARIA-H: includes microhemorrhage and superficial siderosis.
First Onset of ARIA in TRAILBLAZER-ALZ 6
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 included 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).5 Therefore, the modified titration regimen is the recommended dosage for donanemab.4
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.5
In TRAILBLAZER-ALZ 6, ARIA-E occurred in
- 24% of participants in the standard dosing regimen, and
- 14% in the modified titration regimen at the 24-week primary endpoint. 5
The majority of the first ARIA-E events occurred within the first 6 infusions (Figure 4). No serious ARIA-E events based on magnetic resonance imaging (MRI) or treatment-emergent adverse event (TEAE) cluster occurred in the standard dosing regimen, and 1 serious ARIA-E event occurred in the modified titration regimen at infusion 7.1
Figure 4. Timing of First ARIA-E Event by Donanemab Infusion Number Based on MRI or TEAE Cluster: TRAILBLAZER-ALZ 61
Figure 4 description: The modified titration regimen had lower rates of ARIA-E compared with the standard dosing regimen. In both treatment arms, the majority of first ARIA-E events occurred within the first 6 infusions.
Abbreviations: ARIA-E = amyloid-related imaging abnormalities-edema; MRI = magnetic resonance imaging; TEAE = treatment-emergent adverse event.
In the TRAILBLAZER-ALZ 6 study, ARIA-H occurred in
- 25% of participants in the standard dosing regimen, and
- 20% in the modified titration regimen at 24 weeks.5
The time to first event of ARIA-H did not differ in the modified titration regimen compared with the standard dosing regimen.1 No events of serious ARIA-H occurred in the TRAILBLAZER-ALZ 6 study.5
Enclosed Prescribing Information
KISUNLA® (donanemab-azbt) injection, for intravenous use, Lilly
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
- Data on file, Eli Lilly and Company and/or one of its subsidiaries.
- Sims 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
- Mintun MA, Lo AC, Evans CD, et al. Donanemab in early Alzheimer’s disease. N Engl J Med. 2021;384(18):1691-1704. https://doi.org/10.1056/NEJMoa2100708
- Kisunla [package insert]. Indianapolis, IN: Eli Lilly and Company; 2025.
- Wang 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. 2025;21(8):100266. https://doi.org/10.1016/j.tjpad.2025.100266
Appendix
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."1
Date of Last Review: January 13, 2026