From the Guidelines
Donanemab has shown efficacy in patients with early symptomatic Alzheimer's disease who have tau and amyloid deposition on positron-emission tomography (PET) scans, with the most recent study suggesting its potential in slowing down memory and thinking problems 1. The study tested donanemab in patients with early Alzheimer's disease, dividing them into two groups: one receiving donanemab through an IV every 4 weeks and the other receiving a placebo. After 76 weeks, the donanemab group had slightly better scores on a test measuring thinking and daily activities compared to the placebo group. The medicine also effectively removed amyloid from the brain, which is thought to harm brain cells in Alzheimer's disease. However, most other tests did not show significant differences between the two groups, indicating that donanemab may help slow down Alzheimer's disease, but its benefits are modest.
Key Findings
- Donanemab has been investigated as an anti-amyloid therapy, with amyloid-PET quantification used for patient selection, evaluation of target-engagement, and assessment of drug effectiveness 1.
- The use of blood biomarkers (BBMs) as a pre-screening step in clinical trials for Alzheimer's disease is being explored, with plasma p-tau217 assay used to identify individuals with pre-clinical AD in the TRAILBLAZER-ALZ trial evaluating donanemab 1.
- Amyloid PET is sensitive and specific for detecting the likely presence of Aβ neuritic plaques, one of the core molecular features of AD pathologic change, and may provide valuable information that influences diagnostic confidence and management 1.
Clinical Implications
- Donanemab may be a useful treatment option for patients with early symptomatic Alzheimer's disease who have tau and amyloid deposition on PET scans.
- The use of amyloid-PET quantification and BBMs may help guide therapeutic strategies and improve patient management.
- However, the benefits of donanemab are modest, and it is not a cure for Alzheimer's disease.
From the Research
Efficacy of Donanemab in Early Symptomatic Alzheimer's Disease
- Donanemab, an anti-amyloid beta antibody, has shown efficacy in patients with early symptomatic Alzheimer's disease who have tau and amyloid deposition on positron-emission tomography (PET) scans 2, 3, 4.
- The TRAILBLAZER-ALZ trial demonstrated that donanemab resulted in a better composite score for cognition and the ability to perform activities of daily living than placebo at 76 weeks 2.
- The TRAILBLAZER-ALZ 2 trial confirmed the efficacy of donanemab in reducing amyloid plaque accumulation and cognitive decline, with a 35% slowing of decline on the Integrated Alzheimer's Disease Rating Scale (iADRS) and a 36% slowing on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) 3.
- The JAMA study found that donanemab significantly slowed clinical progression at 76 weeks in participants with low/medium tau and in the combined low/medium and high tau pathology population 4.
Safety and Tolerability of Donanemab
- Donanemab has been associated with amyloid-related imaging abnormalities (ARIA) of edema or effusion, which occurred in 24.0% of participants in the donanemab group and 2.1% in the placebo group 4.
- Infusion-related reactions occurred in 8.7% of participants with donanemab and 0.5% with placebo 4.
- Donanemab appears generally well-tolerated, but may have higher rates of severe side effects, such as ARIA, that could lead to death 5.
Clinical Relevance and Future Directions
- Donanemab represents a promising treatment option for patients with early-stage Alzheimer's disease, specifically targeting and reducing amyloid beta plaques 3.
- Further research is essential to validate long-term outcomes, assess effectiveness across diverse populations, and refine dosing strategies to minimize side effects 3, 5.
- The development of donanemab signifies progress in Alzheimer's disease treatment, and its expected FDA approval will give clinicians access to another disease-modifying drug 5.