A New Era in Alzheimer's and Dementia Treatment
For decades, treatments for Alzheimer's disease, the most common form of dementia, focused only on managing symptoms. New advancements have opened a new chapter, introducing drugs that address one of the underlying biological causes of the disease. These monoclonal antibody therapies target and clear amyloid plaques, a hallmark of Alzheimer's, from the brain. While they don't cure dementia, they can significantly slow its progression in eligible patients.
Donanemab (Kisunla)
In July 2024, the U.S. Food and Drug Administration (FDA) granted traditional approval for donanemab, marketed under the brand name Kisunla. Manufactured by Eli Lilly, this drug is indicated for patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease. Its mechanism of action involves targeting a modified form of beta-amyloid, effectively clearing the plaques from the brain over time.
Clinical trial results demonstrated that donanemab can slow cognitive and functional decline in patients. A key feature of this treatment is that it can be stopped once sufficient amyloid has been cleared from the brain, as confirmed by follow-up PET scans. This offers a unique treatment course compared to other anti-amyloid therapies. Donanemab is administered via an intravenous (IV) infusion once every four weeks.
Lecanemab (Leqembi)
Lecanemab, sold under the brand name Leqembi, received traditional FDA approval in July 2023 for the treatment of early Alzheimer's disease. Developed by Eisai and Biogen, Leqembi is also a monoclonal antibody that works by targeting and neutralizing beta-amyloid protofibrils, which are aggregates of the amyloid protein. By doing so, it helps the body clear these abnormal proteins from the brain.
In clinical trials, lecanemab demonstrated a moderate slowing of cognitive and functional decline in patients with early Alzheimer's. Patients eligible for this treatment must also have confirmed amyloid pathology in their brain. Lecanemab is administered via IV infusion every two weeks.
How Do These Anti-Amyloid Therapies Compare?
While both donanemab and lecanemab offer a similar disease-modifying approach, there are differences in their specifics, particularly regarding administration and the precise form of amyloid they target. It's crucial for patients and their care teams to weigh these factors.
| Feature | Donanemab (Kisunla) | Lecanemab (Leqembi) |
|---|---|---|
| Manufacturer | Eli Lilly | Eisai/Biogen |
| Approval Date | July 2024 (FDA) | July 2023 (FDA) |
| Mechanism | Monoclonal antibody targeting modified beta-amyloid plaques | Monoclonal antibody targeting beta-amyloid protofibrils |
| Indication | Early symptomatic Alzheimer's (MCI or mild dementia) | Early symptomatic Alzheimer's (MCI or mild dementia) |
| Administration | IV infusion every 4 weeks | IV infusion every 2 weeks |
| Stopping Treatment | Can be stopped once amyloid is cleared | Continuous therapy (currently) |
Important Risks and Considerations
As with many potent medications, these anti-amyloid therapies come with risks. The most significant is a condition known as amyloid-related imaging abnormalities, or ARIA. ARIA can manifest as temporary brain swelling (ARIA-E) or microbleeds (ARIA-H), which are visible on an MRI scan. While often asymptomatic, severe cases can lead to serious complications. For this reason, regular MRI monitoring is required during treatment.
Other potential risks and considerations include:
- Genetic Risk: Individuals who carry the ApoE ε4 gene have a higher risk of developing ARIA. Genetic testing is recommended before starting treatment to inform the risk assessment.
- Existing Conditions: Certain health conditions, such as a history of stroke, or the use of blood thinners, may increase the risk of bleeding in the brain.
- Eligibility: These treatments are for patients in the early stages of Alzheimer's and with confirmed amyloid plaques. They are not appropriate for advanced-stage dementia or other types of dementia.
The Importance of Early Diagnosis
The emergence of disease-modifying drugs highlights the critical need for early and accurate dementia diagnosis. Identifying Alzheimer's in its earliest stages—mild cognitive impairment or mild dementia—allows patients to become eligible for these therapies and potentially benefit most from them.
Patients showing signs of early cognitive decline should consult with a neurologist or dementia specialist to explore diagnostic options. Confirmation of amyloid pathology, often through PET scans or CSF analysis, is a prerequisite for treatment.
Looking Beyond Anti-Amyloid Therapies
While anti-amyloid drugs are the current breakthrough, they are not the only area of research. Other strategies in the pipeline include:
- Tau-targeting therapies: Investigating drugs to combat the neurofibrillary tangles of tau protein, another pathology associated with Alzheimer's.
- Neuro-inflammation reduction: Developing treatments that target chronic inflammation in the brain.
- Alternative targets: Exploring novel small molecules and vaccines that address other aspects of Alzheimer's pathology.
- Symptomatic treatments: While not new, drugs like cholinesterase inhibitors (e.g., Aricept) and glutamate regulators (e.g., Namenda) still play a role in managing cognitive symptoms.
- Addressing Agitation: Brexpiprazole (Rexulti) is an FDA-approved drug for treating agitation associated with dementia due to Alzheimer's.
Conclusion: A Foundation for Future Progress
No single drug can yet "beat" dementia, which is a complex condition with various underlying causes. However, the approval of donanemab and lecanemab marks a pivotal moment, shifting the focus from purely symptomatic relief to disease modification. For those in the early stages of Alzheimer's, these new treatments offer tangible hope by extending the time they have with better cognitive function. This represents a foundational step forward, fueling further research into more effective, and potentially multimodal, therapies for the future. For additional information and resources, visit the Alzheimer's Association website.
