The key difference between Aducanumab and Lecanemab is that Aducanumab binds to aggregated forms of amyloid-β, while Lecanemab binds to protofibrils, which are smaller and more soluble forms of amyloid-β.
Alzheimer’s disease is a neurodegenerative disease characterized by the presence of plaques forming extracellularly in the brain. These plaques consist mainly of amyloid-β, a peptide formed by cleaving the amyloid precursor protein. The distinct characteristics of amyloid-β plaques, such as their solubility, quantity, and composition, may affect the disease state. Amyloid-β causes synaptic impairment, neuronal death, and progressive neurodegeneration, which leads to dementia and cognitive impairment associated with AD. Aducanumab and Lecanemab are monoclonal antibodies used for Alzheimer’s patients with mild cognitive impairment or dementia stage. They are recombinant monoclonal IgG1 antibodies that target extracellular amyloid-β plaques in the brain. These are new and expensive drugs, and their long-term safety and efficacy are still being studied. Therefore, talking to a doctor about the risks and benefits of Aducanumab and Lecanemab is important before deciding the right medication for individual cases.
CONTENTS
1. Overview and Key Difference
2. What is Aducanumab
3. What is Lecanemab
4. Similarities – Aducanumab and Lecanemab
5. Aducanumab vs. Lecanemab in Tabular Form
6. Summary – Aducanumab vs. Lecanemab
What is Aducanumab?
Aducanumab is a monoclonal antibody used for Alzheimer’s patients with mild cognitive impairment or dementia stage. It is a recombinant monoclonal IgG1 antibody that targets extracellular amyloid-β plaque in the brain. The Fab region of Aducanumab binds to the amyloid-β at the Phe4, His6, Glu3, and Arg5 residues, thereby slowing the progression rate of Alzheimer’s disease. Aducanumab is marketed as Aduhelm and received FDA approval in 2021 under the accelerated approval pathway. It is a new and expensive drug, and its long-term safety and efficacy are yet to be fully studied.
Figure 01. X-ray Structure of the Adumab Domain of Aducanumab
Aducanumab is only available as an intravenous infusion and reaches maximum plasma concentration 3 hours after the infusion. Aducanumab has a longer duration of action with a terminal half-life of 24.8 days; therefore, it is given once every four weeks. During metabolism, Aducanumab is catabolized into smaller oligopeptides and individual amino acids, which in turn will be recycled or subject to obtain energy. The dose-limiting toxicity of Aducanumab includes transient edema and microhemorrhages in the brain. Therefore, getting brain scans before and during treatment is important to monitor for amyloid-related imaging abnormalities (ARIA). Aducanumab is not recommended for people with certain medical conditions, such as bleeding disorders or a history of stroke.
What is Lecanemab?
Lecanemab is another humanized IgG1 monoclonal antibody indicated for Alzheimer’s patients with mild cognitive impairment and mild dementia stage. It targets amyloid-β plaques and works on Aβ oligomers, protofibrils, and insoluble fibrils to lower the amyloid-β plaques in the brain. It is marketed as Leqembi and is available only upon prescription. Lecanemab was approved by the FDA in 2023 under the traditional approval pathway, which requires evidence of clinical benefit in two adequate and well-controlled trials. In a clinical trial of people with early Alzheimer’s disease, Lecanemab was shown to slow the progression of cognitive decline by 27% compared to placebo.
Intravenous administration of Lecanemab reaches peak plasma concentration six weeks after administration. Proteolytic enzymes also degrade it in a manner that other IgGs are metabolized. The terminal half-life of Lecanemab is 5-7 days. Lecanemab is not recommended for people with certain medical conditions, such as bleeding disorders or a history of stroke. Lecanemab is also a new and expensive drug, and its long-term safety and efficacy are still being studied. Therefore, it is important to talk to a doctor about the risks and benefits of Lecanemab before deciding if it is right for the given condition.
What are the Similarities Between Aducanumab and Lecanemab?
- The FDA has approved Aducanumab and Lecanemab to treat Alzheimer’s disease.
- They are monoclonal antibodies that target amyloid beta.
- Both drugs are administered by intravenous infusion.
- Both drugs can cause side effects, including infusion-related reactions and amyloid-related imaging abnormalities.
- They are expensive.
- Both drugs are new, and their long-term safety and efficacy are still being studied.
- Neither drug is a cure for Alzheimer’s disease, but they may help slow its progression.
What is the Difference Between Aducanumab and Lecanemab?
Aducanumab and Lecanemab are both monoclonal antibodies that target amyloid-β, a protein that forms plaques in the brains of people with Alzheimer’s disease. They are also both approved by the FDA to treat Alzheimer’s disease. However, there is a distinct difference between Aducanumab and Lecanemab. Aducanumab binds to aggregated forms of amyloid-β when treating Alzheimer’s disease. In contrast, Lecanemab binds to smaller and more soluble protofibrils. Therefore, Lecanemab is more effective at removing amyloid-β from the brain.
Aducanumab received FDA approval in 2021 under the accelerated approval pathway, while Lecanemab received FDA approval in 2023 under the traditional approval pathway. Moreover, Aducanumab is sold under the brand name of Aduhelm, while Lecanemab is sold under Leqembi.
Below is a summary of the difference between Aducanumab and Lecanemab in tabular form for side-by-side comparison.
Summary – Aducanumab vs. Lecanemab
Aducanumab and Lecanemab are two monoclonal antibody drugs approved by the FDA for treating Alzheimer’s disease. They both target amyloid-β, a protein associated with Alzheimer’s disease, but they have distinct differences. Aducanumab binds to aggregated forms of amyloid-β, while Lecanemab binds to smaller and more soluble protofibrils, potentially making Lecanemab more effective at removing amyloid-β from the brain. Thus, this is the key difference between Aducanumab and Lecanemab. Both drugs are relatively new and expensive, and their long-term safety and efficacy are still under study. It’s crucial for individuals considering these treatments to consult with a healthcare professional to weigh the risks and benefits based on their specific circumstances.
Reference:
1. Verger, Antoine, et al. “FDA approval of lecanemab: The real start of widespread amyloid pet use? — the EANM Neuroimaging Committee perspective.” European Journal of Nuclear Medicine and Molecular Imaging, vol. 50, no. 6, 2023, pp. 1553–1555.
2. Verger, Antoine, et al. “FDA approval of lecanemab: The real start of widespread amyloid pet use? — the EANM Neuroimaging Committee perspective.” European Journal of Nuclear Medicine and Molecular Imaging, vol. 50, no. 6, 2023, pp. 1553–1555.
Image Courtesy:
1. “Structure of AduFab with bound Aβ1-11 peptide” By Lewisiscrazy – Own work (CC BY-SA 4.0) via Commons Wikimedia