18.07.2023

Donanemab and Lecanemab in Alzheimer's Treatment: A Comparative Analysis

Donanemab and lecanemab are monoclonal antibodies devised to clear the amyloid plaque that accumulates in the brains of Alzheimer's patients. Recent clinical trials, notably TRAILBLAZER-ALZ 2 for donanemab and CLARITY AD for lecanemab, have indicated that these antibodies can not only slow the progression of dementia in patients with early-stage Alzheimer's disease but also potentially improve their cognitive abilities. While both share a similar objective, there are critical distinctions between them. In this article, we delve into their similarities and differences.

1. Binding to Amyloid Plaque:

Amyloid plaques, a hallmark of Alzheimer's, accumulate in the brain over time. Medications formulated to target these plaques interact with the plaques at varied stages of their development. Specifically, lecanemab attaches itself to amyloid in its early stage as it starts forming fibers. Contrastingly, donanemab acts when these fibers conglomerate to shape a more substantial plaque in the brain. 

 

2. Rate of Amyloid Plaque Removal:

Donanemab is notable for its ability to facilitate rapid plaque removal, leading to a marked decline in amyloid presence as early as six months post-treatment initiation. Lecanemab, while potentially slower in eradicating plaques, is adept at diminishing oligomers, thereby mitigating brain damage. 

 

3. Amyloid-related imaging abnormalities

ARIA denotes a spectrum of visual patterns discerned via Magnetic Resonance Imaging (MRI) of the brain. Such abnormalities are frequently spotted in Alzheimer's Disease (AD) patients undergoing treatments with monoclonal antibodies, including donanemab and lecanemab. They can signal side effects such as edema or hemorrhage. Notably, donanemab has been associated with a more occurrence rate of ARIA, predominantly in the initial treatment phases. In contrast, ARIA manifestations tend to manifest over a more extended period with lecanemab. 

 

4.Treatment regimen

Both these therapeutic agents are administered intravenously.
While
donanemab is typically dispensed once a month, lecanemab requires bi-weekly dosing.

In summary, Lecanemab and Donanemab exhibit distinct approaches and effects in Alzheimer's treatment, with differences in plaque interaction, amyloid removal rates, and ARIA occurrence. Lecanemab targets early-stage plaques and oligomers more gradually, while Donanemab offers rapid plaque reduction but higher initial ARIA rates. Their varied dosing schedules further emphasize the necessity for individualized treatment strategies in managing Alzheimer's Disease.

 

References:

1.Zügige Entfernung der Amyloid-Plaques durch Donanameb möglich

2. Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evalutaing Aducanumab in Patients With Early Alzheimer Disease

3. A Study to Confirm Safety and Efficacy of Lecanemab in Paricipants With Early Alzheimer's Disease (CLARITY AD)

 

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