Is Donanemab suitable for moderate Alzheimer's disease?

Donanemab (Donanemab) is a monoclonal antibody targeting β- amyloid plaques. It is currently mainly studied for the treatment of early Alzheimer's disease (including mild cognitive impairment and mild Alzheimer's disease). In the TRAILBLAZER-ALZ 2 clinical trial results announced in 2023, donenezumab showed positive efficacy in clearing amyloid deposition in the brain and slowing cognitive and functional decline, but the study subjects were limited to patients in the early stages.

For patients with moderate Alzheimer's disease, there is currently insufficient clinical evidence to support the safety and effectiveness of donenezumab. The mechanism of donenemumab is to remove amyloid protein accumulated in the brain as early as possible to prevent the progression of the disease. However, in the moderate stage, neuronal damage has become more severe, and simple removal of amyloid protein may be difficult to reverse the continued deterioration of cognitive function, and the therapeutic benefits are limited.

Clinical studies excluded moderately and severely ill patients, mainly based on risk and benefit assessments. Donelizumab may cause "ARIA", an amyloid-related imaging abnormality (brain edema or bleeding), which is more common and at higher risk in people with more severe disease. Therefore, it is currently recommended that donenezumab users be diagnosed as "amyloid positive" and in the early stage through PET or CSF tests, and patients with moderate or above symptoms are clearly excluded.

Taken together, donenezumab is not suitable for moderate Alzheimer's disease. For this type of patients, clinical treatment is still mainly symptomatic treatment (such as cholinesterase inhibitors, NMDA receptor antagonists), combined with non-drug intervention (cognitive training, environmental support, etc.) to help delay functional deterioration. Whether the indications will be expanded in the future still needs to be supported by more clinical data. It is recommended that patients with moderate symptoms should not use such drugs on their own and should conduct individualized assessments under the guidance of a doctor.

Reference materials:https://www.drugs.com/