Hope and Hurdles: The Latest in Alzheimer's Clinical Trials

The landscape of Alzheimer's research is rapidly evolving, bringing both hope and challenges. Recent clinical trials have yielded promising results, offering potential new treatments for this devastating disease.

Recent Breakthroughs:

Two drugs, Lecanemab (Leqembi) and Donanemab (Kisunla), have shown significant promise. Both are monoclonal antibodies designed to remove amyloid plaques, a hallmark of Alzheimer's, from the brain.

• Lecanemab, approved by the FDA in July 2023, slowed cognitive decline by 27% in clinical trials. It works by binding to amyloid beta protofibrils, helping the immune system clear plaques.

• Donanemab, approved in the US in July 2024, demonstrated a roughly 35% slowing of cognitive decline in early-stage Alzheimer's. Notably, patients in trials could discontinue treatment once amyloid plaques were cleared.

While these drugs offer a new approach by targeting the underlying disease, they are not cures. They are most effective in the early stages of Alzheimer's and come with potential side effects, including ARIA (amyloid-related imaging abnormalities), which can cause brain swelling and bleeding.

Ongoing Trials:

Beyond these breakthroughs, numerous clinical trials are exploring diverse therapeutic avenues.

• Semaglutide, a drug already used for diabetes and weight management, is being investigated for its potential neuroprotective effects in two large Phase 3 trials, with results expected by the end of 2025.

• Other trials are exploring innovative biologics like vaccines and cell therapies, as well as medical devices like brain-stimulating headsets.

Challenges and Ethical Considerations:

Despite the progress, significant challenges remain in Alzheimer's clinical trials:

• Recruitment Diversity: Historically, trials have lacked representation from diverse communities, which is crucial for ensuring treatments are effective for all populations.

• Ethical Considerations: Obtaining informed consent from individuals with cognitive impairment is complex. Balancing potential benefits with risks and the burden of treatment (e.g., frequent IV infusions) is essential.

Cost and Access: The high cost of new treatments raises concerns about accessibility. For example, Donanemab's price could be between approximately $80,000 and $110,000 per year.