On July 2, 2024, the US Food and Drug Administration (FDA) granted approval for Eli Lilly’s Kisunla (donanemab-azbt) injection for the treatment of Alzheimer’s disease. This treatment is recommended for patients in the early stages of the disease, specifically those with mild cognitive impairment or mild dementia, as demonstrated in the clinical trials. Kisunla marks the second current FDA-approved drug for Alzheimer’s treatment, following the approval of Leqembi (lecanemab-irmb) injection from Eisai in 2023.

According to the National Institute on Aging (NIA), estimates vary, but it is suggested that more than 6 million Americans, most of them age 65 or older, may have Alzheimer’s. Also, it currently ranks as the seventh leading cause of death in the United States and is the most common cause of dementia among older adults.

In response to this critical need, we will examine the results of the TRAILBLAZER-ALZ 2 Phase III trial, which have revealed the important outcomes that paved the way for approval. Trial participants were analyzed over 18 months in two groupings: one group who was less advanced in their disease (those with low to medium levels of tau protein) and the overall population, which also included participants with high tau levels. Treatment with Kisunla significantly slowed clinical decline in both groups. Those individuals treated with Kisunla who were less advanced in their disease showed a significant slowing of decline of 35% compared with placebo on the integrated Alzheimer’s Disease Rating Scale (iADRS), which measures memory, thinking, and daily functioning. In the overall population, the response to treatment was also statistically significant using the iADRS at 22%. Among the two groups analyzed, participants treated with Kisunla had up to a 39% lower risk of progressing to the next clinical stage of the disease than those taking placebo. Kisunla can cause amyloid-related imaging abnormalities (ARIA), which is a potential side effect with amyloid plaque-targeting therapies that does not usually cause symptoms. ARIA can be serious, and life-threatening events can occur.

Below is a brief overview of the study:

A Phase III, Randomized, Open-Label, Multi-Center, Global Study to Determine the Efficacy and Safety A Study of Donanemab (LY3002813) in Participants With Early Alzheimer’s Disease (TRAILBLAZER-ALZ 2)

Study Details | Source

  • Sponsor: Eli Lilly and Company
  • “The reason for this study is to see how safe and effective the study drug donanemab is in participants with early Alzheimer’s disease. Additional participants will be enrolled to an addendum safety cohort. The participants will be administered open-label donanemab.”
  • Interventions: DRUG: Donanemab, DRUG: Placebo
  • Primary Outcomes Measures: 
  • Change From Baseline on the Integrated Alzheimer’s Disease Rating Scale (iADRS) (Overall Population):
    • Integrated Alzheimer’s Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the ADAS-Cog13 and the Alzheimer’s disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. Least Squares (LS) Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline acetylcholinesterase inhibitor (AchI)/Memantine use.
    • Change From Baseline on the Integrated Alzheimer’s Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population): Integrated Alzheimer’s Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer’s disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use.

Will the results of this trial impact the upcoming guidelines or practice parameters?  Can we expect updates from the American Academy of Neurology’s (AAN) on updated treatments? We value your input and encourage you to share your thoughts. Don’t forget to sign up for alerts and stay informed on the latest published guidelines and articles.

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