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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.
How quickly does amyloid reaccumulate after completion of Kisunla™ (donanemab-azbt) treatment?
Participants who stopped donanemab after 24 weeks with amyloid PET levels <11 CL had little amyloid plaque reaccumulation at 18 months. The rate of amyloid reaccumulation is estimated to be 2.80 CL/year, based on a modeling analysis.
See important safety information, including boxed warning, in the attached prescribing information.
Amyloid Reaccumulation After Treatment Completion
TRAILBLAZER-ALZ 2 Study
In the phase 3 TRAILBLAZER-ALZ 2 study, completion of active treatment in the clinical trial was guided by amyloid positron emission tomography (PET) levels measured at week 24 and week 52. Participants were eligible to be switched to placebo if the amyloid plaque level was
- <11 centiloids (CL) on a single PET scan, or
- 11 to <25 CL on 2 consecutive PET scans.1
An analysis was conducted in 111 donanemab-treated participants in the TRAILBLAZER-ALZ 2 study who
- achieved amyloid plaque levels below 11 CL by 24 weeks and switched to placebo, and
- completed amyloid PET scan at week 76.2
These participants had
- baseline mean amyloid plaque level of 80.76 CL (compared with 104.0 CL for overall donanemab-treated population), and
- mean reduction from baseline of 83.18 CL at 24 weeks and 82.93 CL at 76 weeks.2
There was no substantial amyloid reaccumulation from 24 weeks to 76 weeks, with a median amyloid reaccumulation of 0.95 CL (first quartile -4.50 CL, third quartile 4.63 CL) in these participants.2
Amyloid PET values may increase after treatment with donanemab is stopped. There is no data beyond the 76-week duration of the TRAILBLAZER-ALZ 2 study to guide whether additional dosing with donanemab may be needed for longer-term clinical benefit.3
These results will be further evaluated in the long-term extension study period of the TRAILBLAZER-ALZ 2 study.1
Modeling
Changes in individual participant amyloid plaque trajectories were used to inform a model to predict the rate of amyloid reaccumulation during an off-treatment period. Using a scenario with a post-treatment baseline amyloid level <11 CL in the model, the simulations estimated a median amyloid reaccumulation rate of 2.80 CL/year off treatment.3,4
This finding is supported by natural amyloid accumulation modeling studies, showing approximately 3.3 CL/year estimated natural rate of amyloid accumulation.5
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
2Data on file, Eli Lilly and Company and/or one of its subsidiaries.
3Kisunla [package insert]. Indianapolis, IN: Eli Lilly and Company; 2024.
4Gueorguieva I, Chow K, Chua L, et al. Donanemab exposure-efficacy and exposure-safety (ARIA-E) relationships in participants with Alzheimer’s disease: results from the TRAILBLAZER-ALZ clinical program. Abstract presented at: International Conference on Alzheimer’s and Parkinson’s Disease; March 5-9, 2024; Lisbon Portugal.
5Jagust WJ, Landau SM, Alzheimer's Disease Neuroimaging Initiative. Temporal dynamics of β-amyloid accumulation in aging and Alzheimer disease. Neurol. 2021;96(9):e1347-e1357. http://dx.doi.org/10.1212/wnl.0000000000011524
Date of Last Review: October 12, 2023