Search Kisunla (type in keywords)

Search Medical Information

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.

Can Kisunla® (donanemab-azbt) be continued in patients with recurrent ARIA?

There is limited experience with recurrent episodes of ARIA-E. The risk of ARIA recurrence is related to the radiographic severity of the initial ARIA episode and to the number of previous ARIA episodes.

US_cFAQ_DON504A_ARIA_RECURRENCE_ESAD_OFF_reviewed

See important safety information, including boxed warning, in the attached prescribing information.

Recurrent Episodes of ARIA in the Donanemab Clinical Trials

Amyloid-related imaging abnormalities (ARIA) 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.^1,2 The 2 forms of ARIA are

amyloid-related imaging abnormalities-edema (ARIA-E), observed on MRI as vasogenic cerebral edema or sulcal effusions, and
amyloid-related imaging abnormalities-hemosiderin deposition (ARIA-H), which includes microhemorrhage and superficial siderosis.^1-3

These are typically detected on different MRI sequences and are thought to share common underlying pathological mechanisms.^2,3

Amyloid-related imaging abnormalities-hemosiderin deposition associated with monoclonal antibodies directed against aggregated forms of beta amyloid generally occurs in association with an occurrence of ARIA-E; ARIA-H of any cause and ARIA-E can occur together.¹

There is limited experience in participants who

continued dosing through asymptomatic but radiographically mild-to-moderate ARIA-E, or
have experienced recurrent episodes of ARIA-E.¹

Use clinical judgment in considering whether to continue dosing in patients with recurrent ARIA-E.¹

Incidence of ARIA Recurrence

An analysis of ARIA was conducted using data from the placebo-controlled portions of the phase 2 TRAILBLAZER-ALZ and phase 3 TRAILBLAZER-ALZ 2 studies, and an open-label addendum to the TRAILBLAZER-ALZ 2 study.⁴

Participants in the placebo-controlled portions of the phase 2 and phase 3 trials were randomized at the beginning of double-blind treatment in a 1:1 ratio to receive intravenous infusions every 4 weeks of either

donanemab 700 mg for the first 3 doses and 1400 mg thereafter (n=984), or
placebo (n=999).⁴

The dose in the open-label addendum was the same, except that all participants received donanemab (n=1047).⁴

After the first ARIA-E episode

315 of 443 participants (71.1%) were rechallenged with donanemab, and
216 of 315 rechallenged (68.6%) did not experience ARIA-E recurrence.⁴

The highest number of ARIA-E events was 5 in one participant.⁴

Table 1 summarizes the maximum radiographic severity of the second ARIA-E episode in rechallenged participants, and Table 2 summarizes recurrence by apolipoprotein E ε4 (APOE ε4) genotype.

**Table 1.** Maximum Radiographic Severity of Second ARIA-E Episode After Donanemab Treatment Rechallenge^a in the Integrated Placebo-Controlled and Open-Label Addendum⁴
Maximum Radiographic Severity^b During the First ARIA-E Episode	Maximum Radiographic Severity^b During the Second ARIA-E Episode in Rechallenged Participants
	None n (%)	Asymptomatic			Symptomatic
	None n (%)	Mild n (%)	Moderate n (%)	Severe n (%)	Mild n (%)	Moderate n (%)	Severe n (%)
Asymptomatic
Mild (Nj=155, Nx=126)	92 (73.0)	18 (14.3)	13 (10.3)	0 (0.0)	0 (0.0)	2 (1.6)	1 (0.8)
Moderate (Nj=199, Nx=141)	97 (68.8)	13 (9.2)	28 (19.9)	1 (0.7)	0 (0.0)	2 (1.4)	0 (0.0)
Severe (Nj=11, Nx=6)	4 (66.7)	0 (0.0)	1 (16.7)	0 (0.0)	0 (0.0)	0 (0.0)	1 (16.7)
Symptomatic
Mild (Nj=18, Nx=16)	9 (56.3)	3 (18.8)	2 (12.5)	0 (0.0)	1 (6.3)	1 (6.3)	0 (0.0)
Moderate (Nj=40, Nx=21)	11 (52.4)	1 (4.8)	4 (19.0)	0 (0.0)	2 (9.5)	2 (9.5)	1 (4.8)
Severe (Nj=20, Nx=5)	3 (60.0)	1 (20.0)	0 (0.0)	0 (0.0)	0 (0.0)	1 (20.0)	0 (0.0)

Abbreviations: ARIA-E = amyloid-related imaging abnormalities-edema observed on MRI as vasogenic cerebral edema or sulcal effusions; MRI = magnetic resonance imaging; Nj = number of participants with ARIA-E episode; Nx = number of participants rechallenged with donanemab after the first ARIA-E episode; n = number of participants rechallenged with donanemab after first ARIA-E episode and with the first and the second ARIA-E episode in the specified severity category; % = n/Nx.

^aParticipants received at least 1 donanemab dose after the resolution of the first ARIA-E episode.

^bMaximum radiographic severity of ARIA events were rated as mild, moderate, or severe.

**Table 2.** Symptomatic and Asymptomatic ARIA-E After Donanemab Treatment Rechallenge^a by APOE ε4 Carrier Status in the Integrated Placebo-Controlled and Open-Label Addendum⁴
Outcome During the First ARIA-E Episode by *APOE* ε4 Carrier Status	Outcome During the Second ARIA-E Episode in Rechallenged Participants
	None n (%)	Asymptomatic n (%)	Symptomatic n (%)
Noncarrier (N=682, Nj=86, Nx=55)	36 (65.5)	18 (32.7)	1 (1.8)
Asymptomatic (Nj=67, Nx=45)	30 (66.7)	15 (33.3)	0 (0.0)
Symptomatic (Nj=19, Nx=10)	6 (60.0)	3 (30.0)	1 (10.0)
Heterozygote (N=1057, Nj=239, Nx=178)	126 (70.8)	43 (24.2)	9 (5.1)
Asymptomatic (Nj=198, Nx=153)	111 (72.5)	37 (24.2)	5 (3.3)
Symptomatic (Nj=41, Nx=25)	15 (60.0)	6 (24.0)	4 (16.0)
Homozygote (N=282, Nj=117, Nx=82)	54 (65.9)	24 (29.3)	4 (4.9)
Asymptomatic (Nj=100, Nx=75)	52 (69.3)	22 (29.3)	1 (1.3)
Symptomatic (Nj=17, Nx=7)	2 (28.6)	2 (28.6)	3 (42.9)
All participants^b (N=2031, Nj=444, Nx=315)	216 (68.6)	85 (27.0)	14 (4.4)
Asymptomatic (Nj=366, Nx=273)	193 (70.7)	74 (27.1)	6 (2.2)
Symptomatic (Nj=78, Nx=42)	23 (54.8)	11 (26.2)	8 (19.0)

Note: This analysis includes a participant with questionable ARIA-E.

Abbreviations: APOE ε4 = apolipoprotein subtype E allele 4; ARIA-E = amyloid-related imaging abnormalities-edema observed on MRI as vasogenic cerebral edema or sulcal effusions; MRI = magnetic resonance imaging; N = number of participants in analysis population; Nj = number of participants with ARIA-E episode; Nx = number of participants rechallenged with donanemab after the first ARIA-E episode; n = number of participants rechallenged with donanemab after first ARIA-E episode and with the first and the second ARIA-E episode in the specified severity category; % = n/Nx.

^aParticipants received at least 1 donanemab dose after the resolution of the first ARIA-E episode.

^bIncludes participants with missing APOE ε4 carrier status.

Management of ARIA in TRAILBLAZER-ALZ 2

Study participants with ARIA were managed based on guidelines provided to study investigators. Final management decisions regarding whether to hold or continue study drug were at the investigator’s discretion. In general, dose suspension was recommended for participants with

radiographically moderate or severe asymptomatic ARIA, and
symptomatic ARIA-E or ARIA-H of any radiographic severity.⁵

Dosing could be continued for participants with radiographically mild asymptomatic ARIA-E or ARIA-H. The most conservative guidance was recommended for participants with multiple findings.⁵

An analysis evaluating management decisions in TRAILBLAZER-ALZ 2 showed that in cases of

radiographically mild asymptomatic ARIA, no impact on radiographic resolution or clinical outcome based on whether dosing was continued or suspended was noted
radiographically moderate or severe asymptomatic ARIA, the majority of participants suspended dosing, and
radiographically severe ARIA-E that were managed with continued dosing, a higher frequency of participants had recurrence.⁵

A lower frequency of rechallenge and a higher frequency of recurrence following rechallenge was noted

in initial ARIA episodes across increasing radiographic severity, and
across successive ARIA episodes in the case of radiographically mild asymptomatic ARIA-E.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).

Kisunla [package insert]. Indianapolis, IN: Eli Lilly and Company; 2025.
Sperling 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
Cogswell 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
Zimmer JA, Ardayfio P, Wang H, et al. Amyloid-related imaging abnormalities with donanemab in early symptomatic Alzheimer disease: secondary analysis of the TRAILBLAZER-ALZ and ALZ 2 randomized clinical trials. JAMA Neurol. Published online March 10, 2025. https://doi.org/10.1001/jamaneurol.2025.0065
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Cogswell PM, Andrews TJ, Barakos JA, et al; ASNR Alzheimer’s, ARIA, and Dementia Study Group. Alzheimer's disease anti-amyloid immunotherapies: imaging recommendations and practice considerations for ARIA monitoring. AJNR Am J Neuroradiol. 2025;46(1):24-32. https://doi.org/10.3174/ajnr.A8469

Appendix

The radiographic severity of ARIA associated with donanemab was classified by the criteria shown in Table 3.¹

**Table 3.** ARIA MRI Classification Criteria^1,6
ARIA Type	Radiographic Severity
ARIA Type	Mild	Moderate	Severe
ARIA-E	FLAIR hyperintensity confined to sulcus and/or cortex/subcortex white matter in 1 location <5 cm.	FLAIR hyperintensity 5 to 10 cm in single greatest dimension, or more than 1 site of involvement, each measuring <10 cm.	FLAIR hyperintensity >10 cm with associated gyral swelling and sulcal effacement. One or more separate/independent sites of involvement may be noted.
ARIA-H microhemorrhage^a	≤4 new incident microhemorrhages	5 to 9 new incident microhemorrhages	≥10 new incident microhemorrhages
ARIA-H superficial siderosis^a	1 new^b focal area of superficial siderosis	2 new focal areas of superficial siderosis	>2 new focal areas of superficial siderosis

Abbreviations: ARIA = amyloid-related imaging abnormalities; 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 microhemorrhage and superficial siderosis; FLAIR = fluid attenuation inversion recovery; MRI = magnetic resonance imaging.

^aHemosiderin deposits (microhemorrhage and superficial siderosis) are seen on T2* gradient-recalled echo sequence on MRI. ARIA-H severity score is based on cumulative numbers of treatment-emergent microhemorrhages and regions of superficial siderosis compared with the baseline MRI.

^bIncludes new or worsening superficial siderosis.

Date of Last Review: October 02, 2026

Are you satisfied with this content?

Kisunla ® (donanemab-azbt) injection, for intravenous infusion