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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.
What is the efficacy of Kisunla® (donanemab-azbt) in the treatment of early symptomatic Alzheimer’s disease?
At week 76 of TRAILBLAZER-ALZ 2, donanemab slowed clinical progression by 22.3% (iADRS) and reduced amyloid in 76% of participants (<24.1 CL). In the LTE, early start group had 27% reduction in risk of progression at 3 years versus delayed start group.
See important safety information, including boxed warning, in the attached prescribing information.
Content Overview
TRAIBLAZER-ALZ 2 Trial: Efficacy Results at 76 weeks
The Appendix provides a description of the donanemab phase 3 clinical studies.
Study Design and Participants
The safety and efficacy of donanemab were evaluated in TRAILBLAZER-ALZ 2, a phase 3, placebo-controlled 76-week study. This study enrolled adults aged 60 to 85 years with early symptomatic Alzheimer's disease (AD), defined as
- prodromal AD, the symptomatic phase of AD in which mild cognitive impairment is apparent, or
- AD with mild dementia, in which symptoms are sufficiently severe to meet diagnostic criteria for dementia.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
Tau PET scans were interpreted by visual and quantitative reads and categorized as
- low/medium or
- high tau.1
The Appendix provides a description of the study populations by tau PET level at baseline.
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
Primary and Secondary Clinical Outcomes
Donanemab-treated participants had amyloid plaque clearance as early as week 24 in both the combined and low/medium tau populations (Percentage of Donanemab-Treated Participants With Amyloid Plaque Reduction in TRAILBLAZER-ALZ 2).1,3
Worsening scores on the iADRS have been significantly associated with decreased patient quality of life, as well as increased burden on caregivers and society.4 The iADRS is an integrated score ranging from 0 to 144, and includes the
- Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13-item version (ADAS-Cog13), range 0-85, with higher scores correlating to greater global cognition deficit, and
- Alzheimer’s Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL), range 0 to 59, with lower scores correlating to greater deficit in daily function.5
To align the scales, the ADAS-Cog13 score is multiplied by -1, so that lower iADRS overall score correlates to greater impairment.5
The baseline iADRS score was similar between donanemab and placebo (approximately 104 in the combined population and approximately 106 in the low/medium tau population, on scale of 0 to 144). TRAILBLAZER-ALZ 2 Clinical Outcomes at Week 76 shows that compared with placebo, the donanemab cohort had a slowing of clinical progression at week 76 as evidenced by iADRS scores in the
- combined population (22.3%, p<.001), and
- low/medium tau population (35.1%, p<.001).1
Secondary clinical outcome measures included change from baseline through week 76 in either the combined or low/medium tau population as measured by the
- Clinical Dementia Rating scale sum of boxes (CDR-SB)
- ADAS-Cog13 score
- ADCS-iADL score, and
- MMSE score.1
Participants in the donanemab cohort experienced statistically significantly less decline on these measures at week 76 compared with placebo, in both the combined and low/medium tau populations (TRAILBLAZER-ALZ 2 Clinical Outcomes at Week 76 ).1
Clinical Endpointsa |
Combined Population |
Low/Medium Tau |
||
Donanemab |
Placebo |
Donanemab |
Placebo |
|
Mean baseline |
104.55 |
103.82 |
105.92 |
105.95 |
Change from baseline |
-10.19 |
-13.11 |
-6.02 |
-9.27 |
Difference from placebo (%) |
2.92 (22)d |
NA |
3.25 (35)d |
NA |
Mean baseline |
3.92 |
3.89 |
3.72 |
3.64 |
Change from baseline |
1.72 |
2.42 |
1.20 |
1.88 |
Difference from placebo (%) |
-0.70 (29)d |
NA |
-0.67 (36)d |
NA |
Mean baseline |
28.53 |
29.16 |
27.41 |
27.60 |
Change from baseline |
5.46 |
6.79 |
3.17 |
4.69 |
Difference from placebo (%) |
-1.33 (20)d |
NA |
-1.52 (32)d |
NA |
Mean baseline |
47.96 |
47.98 |
48.20 |
48.56 |
Change from baseline |
-4.42 |
-6.13 |
-2.76 |
-4.59 |
Difference from placebo (%) |
1.70 (28)d |
NA |
1.83 (40)d |
NA |
MMSEb |
||||
Mean baseline |
22.52 |
22.20 |
23.11 |
22.88 |
Change from baseline |
-2.47 |
-2.94 |
-1.61 |
-2.09 |
Difference from placebo (%) |
0.47 (16)f |
NA |
0.48 (23)g |
NA |
Abbreviations: ADAS-Cog13 = Alzheimer’s Disease Assessment Scale – 13-item Cognitive Subscale; ADCS-iADL = Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living subscale; CDR-SB = Clinical Dementia Rating Scale – Sum of Boxes; iADRS = integrated Alzheimer’s Disease Rating Scale; NCS2 = natural cubic spline with 2 degrees of freedom; MMRM = mixed model for repeated measures; MMSE = Mini-Mental State Examination; NA = not applicable.
aClinical outcomes were scored as follows: iADRS range from 0 to 144, with lower scores indicating greater impairment; CDR-SB scores range from 0 to 18, with higher scores indicating greater impairment; ADAS-Cog13 scores range from 0 to 85, with higher scores indicating a greater deficit; ADCS-iADL scores range from 0 to 59, with lower scores indicating greater impairment; MMSE scores range from 0 to 30, with lower scores indicating greater impairment.
bAssessed using NCS2 analysis.
cGated outcome.
dp<.001 vs placebo.
eAssessed using MMRM analysis.
fp=.01 vs placebo.
gp=.02 vs placebo.
Key Biomarker Outcomes
Secondary biomarker outcome measures included
- percentage of participants with amyloid reduction to minimal levels (ie, <24.1 CL on amyloid PET) at 24 and 76 weeks, and
- change from baseline in amyloid plaque levels at 76 weeks.1
Donanemab-treated participants met eligibility to switch to placebo1,6 and had amyloid reduction to minimal levels1 as early as week 24 in both the combined and low/medium tau populations (Percentage of Donanemab-Treated Participants With Amyloid Plaque Reduction in TRAILBLAZER-ALZ 2). In contrast, ≤0.3% of participants receiving placebo had amyloid reduction to minimal levels at all time points assessed (p<.0001 vs donanemab).1
|
Combined Population, % (n/N) |
Low/Medium Tau Population, % (n/N) |
||||
Week 24 |
Week 52 |
Week 76 |
Week 24 |
Week 52 |
Week 76 |
|
17 |
47 |
69 |
20 |
52 |
74 |
|
Amyloid plaque reduction to minimal levelsc |
30 |
66 |
76 |
34 |
71 |
80 |
Abbreviations: CL = centiloids; PET = positron emission tomography.
aEligibility criteria: amyloid plaque level of <11 CL on any single amyloid PET scan or 11 to <25 CL on 2 consecutive scans.
bIncluded participants from unscheduled visits at each time point.
cDefined as <24.1 CL on amyloid PET scan, consistent with a negative visual read.
As shown in Change From Baseline in Amyloid Plaque Levels at Week 76 in TRAILBLAZER-ALZ 2, donanemab-treated participants had statistically significantly greater amyloid plaque reduction from baseline compared with placebo-treated participants as assessed by amyloid PET measurement in the
- combined population (-87 CL), and
- low/medium tau population (-88 CL).1
Placebo-treated participants had a change of -0.7 CL in the combined population and 0.2 CL in the low/medium tau population at week 76.1
|
Combined Population |
Low/Medium Tau |
||
Donanemab |
Placebo |
Donanemab |
Placebo |
|
Amyloid beta PET centiloid |
||||
Mean baseline |
104.0 |
101.8 |
103.0 |
100.9 |
Change from baseline (%) |
-87.0 (-83.7) |
-0.7 |
-88.0 (-85.5) |
0.2 |
Difference from placebo |
-86.4b |
NA |
-88.2b |
NA |
Abbreviations: MMRM = mixed model for repeated measures; NA = not applicable; PET = positron emission tomography.
aChange from baseline derived using MMRM methodology with fixed factors for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, baseline tau category, and age at baseline.
bp<.0001 vs placebo.
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
A reduction in plasma P-tau217 was observed with donanemab compared to placebo in the combined and low/medium tau populations (Change From Baseline in Plasma P-tau217 at Week 76 in TRAILBLAZER-ALZ 2).1,3
|
Combined Population |
Low/Medium Tau |
||
Donanemab |
Placebo |
Donanemab |
Placebo |
|
Mean baseline |
0.67 |
0.66 |
0.62 |
0.59 |
Change from baseline (% of original value) |
-0.19 (-35.0) |
0.03 |
-0.22 (-39.0) |
0.04 |
Difference from placebo |
-0.22b |
NA |
-0.25b |
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.
Back to ⇒ Content Overview
Exploratory Outcomes: Time prolonged in current disease state
The TRAILBLAZER-ALZ 2 study evaluated the efficacy of donanemab to prolong time in the current disease state for participants as exploratory outcomes by assessing the
- delay in clinical progression on the iADRS and CDR-SB (ie, months saved with treatment)
- risk of progression to a later stage using CDR-Global (CDR-G), and
- probability of remaining stable at 1 year on the CDR-SB (ie, nonprogressing).1
Donanemab-treated participants experienced statistically significantly less disease progression compared with placebo in all the time-based efficacy analyses.1
Assessing Delay in Clinical Progression
The delay in clinical progression due to donanemab treatment as assessed by the iADRS and CDR-SB was estimated using a time-progression model for repeated measures (PMRM).1,6
As summarized in Delayed Disease Progression at 76 Weeks in TRAILBLAZER-ALZ 2, donanemab treatment statistically significantly delayed disease progression at week 76 compared with placebo as measured by the iADRS and CDR-SB in the
- combined population, and
- low/medium tau population.1
|
||
Combined populationd |
||
Months saved vs placebo |
2.5 |
5.4 |
Percent time savings |
14.1 |
31 |
P value vs placebo |
<.001 |
<.001 |
Low/medium tau population |
||
Months saved vs placebo |
4.4b |
7.5 |
Percent time savings |
24.9 |
42.9 |
P value vs placebo |
<.001 |
<.001 |
Abbreviations: CDR-SB = Clinical Dementia Scale - Sum of Boxes; iADRS = Integrated Alzheimer's Disease Rating Scale.
aiADRS scores range from 0 to 144, with lower scores indicating greater impairment, and CDR-SB scores range from 0 to 18, with higher sores indicating greater clinical impairment.
bThe model did not assume proportional time slowing. Results from the prespecified test of proportional time slowing assumption at 76 weeks was 2.6 months saved, p=.002, but the proportional time slowing assumption was not met for the iADRS (p=.001 from a likelihood ratio test).
cThe model assumed proportional time slowing.
dNot prespecified as gated in the statistical analysis plan.
Risk of Disease Progression
A clinical worsening event was defined as meeting a CDR-G score increase from baseline at 2 consecutive visits. A Cox proportional hazard model was fit to estimate the hazard ratio of progressing to clinical worsening between treatment groups.6
Probability of Remaining Stable at 1 Year (Nonprogressing)
To evaluate the probability of remaining stable, participants' status was classified as "nonprogressing" if their CDR-SB change from baseline was ≤0 at each of the scheduled visits.6
At Week 52, a statistically significantly greater proportion of donanemab-treated participants were non-progressing compared with placebo, in the
- combined population, and
- low/medium tau population (No Progression at 52 Weeks as Measured by CDR-SB in TRAILBLAZER-ALZ 2 ).1
|
Donanemab |
Placebo |
Combined populationc |
||
Estimated percent with no progression |
36% |
23% |
P value vs placebo |
<.001 |
NA |
Low/medium tau population |
||
Estimated percent with no progression |
47% |
29% |
P value vs placebo |
<.00001 |
NA |
Abbreviations: CDR-SB = Clinical Dementia Rating Scale - Sum of Boxes; NA = not applicable.
aNo progression was defined as a CDR-SB score change from baseline of ≤0.
bCDR-SB scores range from 0 to 18, with higher scores indicating greater clinical impairment.
cNot specified as gated in the statistical analysis plan.
Back to ⇒ Content Overview
TRAILBLAZER_ALZ 2 Long Term Extension: Efficacy Results up to 3 Years
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.7
Clinical Efficacy
In the long-term extension, early start treatment
- slowed disease progression with a difference in the CDR-SB of -1.2 (95% CI: -1.7, -0.7), and
- saved approximately 6.9 months as measured by the CDR-SB versus the weighted ADNI control group at 3 years.7
Early start participants who met treatment course completion by 52 weeks of the placebo-controlled period showed a difference on the CDR-SB of -1.3 (95% CI: -1.9, -0.7) versus the ADNI group at 3 years.7
Delayed start participants had more advanced disease and also benefited from donanemab treatment with a difference on the CDR-SB of -0.8 (95% CI: -1.3, -0.3) vs the weighted ADNI group at 1.5 years of treatment.7
On the CDR-G score, treatment with donanemab
- showed a 27% reduction in risk of progression to the next stage of disease in the early start donanemab group compared with the delayed start donanemab group, and
- demonstrated disease modification by continued treatment differences between the early and delayed start groups.7
Biomarkers
In the long-term extension, after 1.5 years from initiation of treatment (154 weeks) delayed start participants experienced similar amyloid reduction (approximately 86 CL) compared to early start participants at 76 weeks.7
A subset of participants who achieved amyloid clearance (<24.1 CL) in the long-term extension period also met the study treatment course completion criteria, defined as an amyloid plaque level of <11 CL on any single PET scan or <25 CL on two consecutive PET scans.7
For delayed-start participants with amyloid PET scans who were randomized to placebo during the 76-week placebo-controlled period and received donanemab in the long-term extension
- 17.6 % (105/595) met treatment course completion criteria at 102 weeks (24 weeks after starting donanemab),
- 51.3 % (267/520) at 130 weeks (52 weeks after starting donanemab), and
- 70.7 % (319/451) at 154 weeks (76 weeks after starting donanemab).7
In participants who met the treatment course completion criteria by week 52 of the placebo-controlled period, the mean amyloid levels remained below 24.1 CL at 3 years.7
Among the subset of patients who met treatment course completion at week 52 of the placebo-controlled period (n=126), 82% had amyloid levels below 24.1 CL at 3 years.6
Of participants initially randomized to donanemab in the placebo-controlled period, 85% met criteria to complete the course of donanemab therapy based on amyloid PET criteria within 3 years.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.
4Wessels AM, Belger M, Johnston JA, et al. Demonstration of clinical meaningfulness of the Integrated Alzheimer’s Disease Rating Scale (iADRS): association between change in iADRS scores and patient and caregiver health outcomes. Alzheimers Dis. 2022;88(2):577-588. https://doi.org/10.3233/JAD-220303
5Wessels AM, Rentz DM, Case M, et al. Integrated Alzheimer's Disease Rating Scale: clinically meaningful change estimates. Alzheimer's Dement. 2022;8(1):e12312. https://doi.org/10.1002/trc2.12312
6Data on file, Eli Lilly and Company and/or one of its subsidiaries.
7Zimmer JA, Sims JR, Evans CD, et al; Alzheimer’s Disease Neuroimaging Initiative. Donanemab in early symptomatic Alzheimer's disease: results from the TRAILBLAZER-ALZ 2 long-term extension. J Prev Alzheimers Dis. 2026;13(2):100446. https://doi.org/10.1016/j.tjpad.2025.100446
8Wang 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
Donanemab Phase 3 Clinical Studies
The effectiveness of donanemab for the treatment of Alzheimer’s disease was established by TRAILBLAZER-ALZ 2,1 which assessed a dosing regimen of 700 mg every 4 weeks for the first 3 doses, and then 1,400 mg every 4 weeks (referred to as standard dosing in TRAILBLAZER-ALZ 6). The TRAILBLAZER-ALZ 6 study8 was conducted to assess different titration regimens, including the modified dosing regimen (ie, currently approved dosing of every 4 weeks with 350 mg the first infusion, 700 mg the second infusion, 1,050 mg the third infusion, and then 1,400 mg thereafter). The currently approved dose demonstrated
Definitions of Populations by Baseline Tau PET Levels
Population Analyzed |
Description |
Low/medium tau |
Population including participants with baseline
|
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.
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Date of Last Review: January 16, 2026