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.

Does APOE ε4 carrier status affect clinical efficacy of Kisunla® (donanemab-azbt)?

In TRAILBLAZER-ALZ 2, donanemab slowed clinical decline in APOE ε4 carriers (heterozygous and homozygous) and noncarriers. Homozygous APOE ε4 carriers had numerically smaller treatment effects than heterozygotes or noncarriers.

in3

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

Subgroup Analyses in TRAILBLAZER-ALZ 2

A phase 3, placebo-controlled 76-week study, TRAILBLAZER-ALZ 2, evaluated the safety and efficacy of donanemab in adults aged 60 to 85 years with early symptomatic Alzheimer's disease.¹

Approximately 70% of clinical trial participants were apolipoprotein subtype E allele 4 (APOE ε4) carriers.¹

Efficacy Outcome Measures by APOE ε4 Carrier Status and Number of APOE ε4 Alleles

Subgroup analyses by APOE ε4 carrier status and number of APOE ε4 alleles were conducted for the integrated Alzheimer's Disease Rating Scale (iADRS; primary endpoint measure).¹

Donanemab treatment showed slowing of clinical decline across APOE ε4 carrier and noncarrier subgroups, as measured by the iADRS in the

overall population, and
low-medium tau population.^1,2

The Appendix provides a description of the study populations by tau positron emission tomography (PET) level at baseline.

At week 76, participants treated with donanemab had a slowing of disease progression on the iADRS in the

overall population by 20.5% in APOE ε4 carriers (p=.004 vs placebo) and 28.0% in APOE ε4 noncarriers (p<.001 vs placebo), and
low-medium tau population by 35.5% in APOE ε4 carriers (p<.001 vs placebo) and 34.6% in APOE ε4 noncarriers (p=.003 vs placebo).^2,3

Consistent with the iADRS findings, donanemab treatment showed slowing of clinical decline across APOE ε4 carrier and noncarrier subgroups in both the overall and low-medium tau populations, as measured by the following secondary efficacy measures

Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)
Alzheimer's Disease Assessment Scale - 13-item Cognitive subscale (ADAS-Cog₁₃)
Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living Scale (ADCS-iADL), and
Mini-Mental State Examination (MMSE).^2,3

Slowing of clinical decline was observed in donanemab-treated APOE ε4 carriers, both heterozygous (ε2/ε4, ε3/ε4) and homozygous (ε4/ε4), and noncarriers across clinical measures with the exception of homozygous carriers on the ADAS-Cog₁₃ in the overall population (Table 1).^2,3

Homozygous APOE ε4 carriers had numerically smaller treatment effects than APOE ε4 heterozygotes or noncarriers but had

the smallest sample size
differences in baseline demographics
more dose pauses, and
fewer participants reaching amyloid plaque reduction to minimal levels (defined as <24.1 centiloids on amyloid PET scan, which is consistent with a negative visual read) by 24 weeks.^3,4

Table 1. Adjusted Mean Difference From Placebo at 76 Weeks by Number of APOE ε4 Alleles: TRAILBLAZER-ALZ 2^1-3

Efficacy Measure	Overall Population			Low-Medium Tau Population
Efficacy Measure	n (PBO, DONA)	Adj. Mean Difference	Percent Slowing	n (PBO, DONA)	Adj. Mean Difference	Percent Slowing
iADRS^a
Noncarrier	(184, 177)	4.58	28.1^b	(116, 118)	4.05	34.8^c
Heterozygote	(350, 312)	2.87	23.8^c	(243, 237)	3.37	37.4^d
Homozygote	(119, 94)	1.01	9.3	(85, 63)	1.91	30.4
CDR-SB
Noncarrier	(184, 181)	-0.76	28.7^d	(116, 121)	-0.80	37.7^c
Heterozygote	(365, 320)	-0.73	33.6^d	(255, 241)	-0.75	43.3^d
Homozygote	(123, 97)	-0.41	17.7	(88, 62)	-0.20	11.9
ADAS-Cog13
Noncarrier	(190, 184)	-2.11	25.3^c	(119, 123)	-1.46	27.7^b
Heterozygote	(363, 324)	-1.59	24.8^c	(254, 243)	-1.89	39.1^d
Homozygote	(124, 99)	0.43	-7.9	(87, 65)	-0.60	18.0
ADCS-iADL
Noncarrier	(186, 181)	2.37	31.4^c	(118, 119)	2.52	40.9^c
Heterozygote	(355, 313)	1.49	26.6^b	(247, 237)	1.63	38.2^c
Homozygote	(120, 97)	1.63	30.4	(86, 84)	1.51	47.7
MMSE
Noncarrier	(190, 182)	0.70	20.1^b	(120, 123)	0.21	8.8
Heterozygote	(363, 320)	0.54	19.8^b	(256, 242)	0.68	33.8^b
Homozygote	(126, 98)	0.03	0.9	(89, 64)	0.31	16.0

Abbreviations: Adj. = adjusted; ADAS-Cog₁₃ = Alzheimer's Disease Assessment Scale - 13-item Cognitive subscale; ADCS-iADL = Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living Scale; APOE ε4 = apolipoprotein subtype E allele 4; CDR-SB = Clinical Dementia Rating Scale - Sum of Boxes; DONA = donanemab; iADRS = integrated Alzheimer's Disease Rating Scale; MMSE = Mini-Mental State Examination; NS = not significant; PBO = placebo.

^aPrimary outcome.

^bp<.05 vs PBO.

^cp<.01 vs PBO.

^dp<.001 vs PBO.

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).

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
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Evans CD, Zimmer JA, Wessels AM, et al. Efficacy of donanemab by APOE ε4 carrier status in TRAILBLAZER-ALZ 2, a phase 3 randomized clinical trial in early symptomatic Alzheimer's disease. Abstract presented at: Clinical Trials on Alzheimer's Disease (CTAD); October 24-27, 2023; Boston, Massachusetts.
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

Appendix

Definitions of Populations by Baseline Tau PET Levels

Table 2. Populations by Baseline Flortaucipir F 18 Tau PET Levels¹

Population Analyzed	Description
Low-medium tau	Population including participants with baseline SUVr ≤1.46 and a topographic deposition pattern consistent with advanced AD neuropathology, or 1.10 ≤ SUVr ≤1.46 and a topographic deposition pattern consistent with moderate AD neuropathology.
High tau	Population including participants with baseline SUVr >1.46 and a topographic deposition pattern consistent with either moderate or advanced AD neuropathology.
Overall population	Population including participants with both low-medium tau and high tau levels.

Population Analyzed

Description

Low-medium tau

Population including participants with baseline

SUVr ≤1.46 and a topographic deposition pattern consistent with advanced AD neuropathology, or
1.10 ≤ SUVr ≤1.46 and a topographic deposition pattern consistent with moderate AD neuropathology.

High tau

Population including participants with baseline SUVr >1.46 and a topographic deposition pattern consistent with either moderate or advanced AD neuropathology.

Overall population

Population including participants with both low-medium tau and high tau levels.

Abbreviations: AD = Alzheimer's disease; PET = positron emission tomography; SUVr = standard uptake value ratio.

Date of Last Review: September 01, 2026

Are you satisfied with this content?

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