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With new Alzheimer’s drugs like lecanemab and more on the horizon, there are outstanding questions that need to be considered by clinicians, patients, and families.

What Do We Know So Far About Lecanemab and Aducanumab for Early Alzheimer’s Disease?

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder with no cure currently available, but there are several medications that can help manage the symptoms. The most promising treatment for AD is Lecanemab, which is now officially available for distribution. Though, you may have also heard about another drug called aducanumab. Both drugs are monoclonal antibodies that target amyloid beta, a protein that plays a role in the development of AD. Both drugs were fast-tracked by the FDA due to the unmet need for effective treatments for Alzheimer’s. Aducanumab received an “accelerated approval” and is still being scrutinized by experts in the field, but lecanemab may have much more support for a successful FDA approval and actual use in the field of Alzheimer’s disease. This would represent a real paradigm shift toward early detection, diagnosis, and treatment.

What is Lecanemab and how does it work? 

Lecanemab is a humanized monoclonal antibody that selectively targets beta-amyloid plaques. Lecanemab was developed by pharmaceutical company Eisai in partnership with Biogen. It has the potential to become the first promising disease-modifying therapy for early Alzheimer’s disease. This novel therapy offers a unique mechanism of action that reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition/function than placebo at 18 months but was associated with adverse events. Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease. Lecanemab works by targeting the small and large beta-amyloid protofibrils that make up amyloid plaques. These plaques are a significant hallmark of Alzheimer’s disease and are thought to contribute to the decline in cognitive function seen in patients with the disease.

What are the benefits of Lecanemab?

Lecanemab has the potential to slow or even stop the progression of Alzheimer’s disease. Study results showed a 27% amyloid reduction over 18 months starting at 6 months. By targeting these plaques, Lecanemab has the potential to slow or even stop the progression of Alzheimer’s disease. Studies also showed that the drug may be more effective in APOE4 non-carriers and maybe less effective in APOE4 homozygotes. PET imagining showed that cerebral spinal fluid (CSF) and plasma markers can also be followed for early and sustained treatment effect, including CSF and plasma p-tau181 levels.

What are the side effects of Lecanemab? 

The most common side effects of Lecanemab include headache and dizziness. More serious side effects are rare but could include infusion reactions and allergic reactions, and potential concerns about an increase in risk of intracranial bleeding. 

Aducanumab 

What is Aducanumab and how does it work?

Aducanumab is a human monoclonal antibody that selectively binds to aggregated forms of beta-amyloid. Similar to Lecanemab, the drug also focuses on the plaques however the mechanism differs. Aducanumab binds to all forms of beta-amyloid, including monomers (single units), oligomers (small clumps), and fibrils (longer strands). Once bound, aducanumab promotes the clearance of beta-amyloid from the brain by macrophages and microglia, which are immune cells that help clean up debris and damaged cells. This plaque clearance mechanism is the way the drug helps slow, and potentially stop, the progression of Alzheimer’s disease. 

What Are the Potential Benefits of Aducanumab? 

Two large clinical trials—the Phase 1b PRIME study and the Phase 3 ENGAGE and EMERGE studies—investigated whether aducanumab could reduce amyloid-beta plaque in the brain and improve cognition and function in people with early Alzheimer’s disease. People with early Alzheimer’s disease who were treated with aducanumab had significant reductions in amyloid plaques compared to those who received placebo. Follow-up questions remain about this clinical efficacy, which is still being investigated.

What are the side effects of Aducanumab? 

Overall, while aducanumab shows some promise as a treatment for Alzheimer’s disease, there are notable risks observed in clinical trials associated with its use that should be considered before beginning treatment. These risks include amyloid deposition, inflammation, and immunogenicity. In translation, these risks were headache, fall and the most concerning side effect being the risk of hemorrhagic stroke. However, these risks must be weighed against the potential benefits of the drug, which include slowing or halting cognitive decline in patients with Alzheimer’s disease – yet there is still ongoing review of the extent of this potential benefit in the context of potential risks and operational irregularities.

Conclusion

So, which drug is more effective? The answer is not yet clear. Lecanemab has been shown to be more effective at reducing levels of amyloid-beta, but aducanumab has been shown to actually remove plaques from the brain. More research is needed to determine which of these drugs is more effective in treating Alzheimer’s disease. Lecanemab is a humanized monoclonal antibody that selectively targets beta-amyloid plaques and has the potential to become the first disease-modifying therapy for early Alzheimer’s disease. This novel therapy offers a unique mechanism of action that may provide significant benefits to patients and their families.

About Isaac Health

Isaac Health is a specialized online memory health service that arranges for patients to meet with a telehealth clinician who can diagnose and treat memory loss, Alzheimer’s dementia, and other related conditions. Isaac Health provides medical care and cognitive therapy for patients in New York, Florida, and North Carolina who are concerned about symptoms of dementia.

For more information or If you’d like to understand whether you or a loved one may benefit from new Alzheimer’s disease treatments, schedule a free no-obligation discovery consultation with a member of the Isaac Health team.

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