FDA Approval of Donanemab: Insights from an Expert
Introduction
First published in August 2024, the recent approval of Donanemab by the USA’s Food and Drug Administration has sparked discussions about the safety and efficacy of monoclonal antibody drugs for Alzheimer’s disease. To clarify the facts, Medical News Bulletin consulted with Professor Sandra Black, MD, a cognitive neurologist and Alzheimer’s specialist at Sunnybrook Research Institute in Canada.
Understanding Monoclonal Antibodies
Alzheimer’s disease has historically been viewed as an untreatable form of dementia. However, since 2021, a new class of anti-Alzheimer’s drugs has emerged. Monoclonal antibodies targeting amyloid proteins are being considered a potential breakthrough. The FDA has approved three antibody-based treatments—Aducanumab, Lecanemab, and Donanemab—aimed at combating the amyloid plaques associated with cognitive decline.
The Mechanism of Action
Cognitive Decline and Amyloid Plaques
Professor Black explains that these monoclonal antibodies are designed to remove amyloid plaques, which are characteristic of Alzheimer’s disease. These plaques form when amyloid beta proteins aggregate on brain cell surfaces, leading to neuronal damage. Although amyloid beta is produced by everyone, individuals with Alzheimer’s fail to clear excess amyloid, resulting in plaque accumulation.
Monoclonal Antibodies Explained
Monoclonal antibodies are engineered in laboratories to target specific proteins. Once injected, these antibodies bind to amyloid proteins, facilitating their removal from the brain. Researchers hope that this process will not only clear existing plaques but also prevent new ones from forming.
Efficacy of Monoclonal Antibodies
Clinical Trial Results
Clinical trials have shown that Lecanemab and Donanemab significantly reduce amyloid plaques in patients with mild Alzheimer’s symptoms. Specifically, Lecanemab has been reported to delay cognitive decline by 27%, while Donanemab has shown an even greater effect, with a 35% reduction. According to Professor Black, this translates to roughly five to six months of slowed cognitive decline, which, while modest, can provide valuable time for patients.
Recent Developments
At the 2025 Alzheimer’s Association International Conference, researchers revealed encouraging findings regarding the real-world effectiveness of Lecanemab and Donanemab. Long-term studies indicate that these monoclonal therapies could help patients retain their cognitive function for four additional years compared to expectations.
Safety Concerns of Monoclonal Antibodies
Risks of Treatment
While monoclonal antibodies offer potential benefits, they are not without risks. Clinical trials have reported abnormalities in brain scans, often identified as microbleeds or brain swelling. Approximately 30–40% of patients treated with these antibodies experienced complications, although most were asymptomatic and resolved over time.
Understanding the Risks
Professor Black notes that the removal of amyloid plaques can lead to blood vessel injuries, resulting in microbleeds or cerebral hemorrhages. This is particularly concerning given that Alzheimer’s patients already have compromised vascular health. Consequently, individuals with pre-existing conditions such as prior strokes or blood vessel issues require careful monitoring when undergoing treatment.
Individualized Treatment Plans
Balancing Benefits and Risks
Monoclonal antibody therapies can delay the progression of Alzheimer’s for a few months but come with risks of serious side effects. While Donanemab appears to be more effective, Lecanemab may present a safer profile. Aducanumab has been discontinued due to its inability to demonstrate superior efficacy or safety.
The Need for Personalized Care
Given the complexity of Alzheimer’s, individual responses to treatment can vary widely. Professor Black emphasizes the importance of informed decision-making, urging patients to work closely with specialized physicians to weigh the risks against the potential benefits of therapy.
Conclusion
As the field of Alzheimer’s research evolves, questions about the amyloid hypothesis remain. Ongoing investigations will continue to shape our understanding of the disease and its treatment. Each patient’s journey with Alzheimer’s is unique, and careful consideration is crucial in navigating treatment options.