Alzheimer's: What the new therapies can really do

The introduction of two new Alzheimer's disease treatments—Lecanemab and Donanemab—has marked a significant shift in the approach to managing this neurodegenerative condition. These therapies, developed by Eisai/Biogen and Lilly respectively, were approved for use in the European Union in 2025. They represent the first class of drugs designed to target the accumulation of amyloid-beta proteins in the brain, which have been linked to the progression of Alzheimer’s since their initial identification under a microscope by Alois Alzheimer over a century ago. According to Dr. Michaela Defrancesco, vice president of the Austrian Alzheimer Society and a dementia specialist, these new medications signal “a step into a new era” in Alzheimer’s treatment. However, she emphasized that they are not a complete breakthrough on a clinical level. The treatments are only suitable for a small subset of patients who are diagnosed in the very early stages of the disease. Despite these limitations, Defrancesco expressed optimism about their potential to catalyze further research into dementia-related conditions. She described the impact as potentially providing a “tailwind effect” for future studies. Both Lecanemab and Donanemab work by targeting amyloid-beta plaques, which are hallmark features of Alzheimer’s pathology. In clinical trials lasting 18 months, these drugs showed some success in slowing down the progression of the disease. Patients treated with them experienced delays in worsening symptoms compared to those who did not receive the therapy. However, the Cochrane Collaboration, a respected international organization that evaluates medical evidence, concluded in a study that none of the existing anti-amyloid antibodies had demonstrated a clinically meaningful effect. This conclusion included substances that had failed to gain approval. Dr. Sascha Alexander Dichter, senior medical director for neuroscience at Lilly Germany, challenged this assessment. He pointed out that the Cochrane analysis combined data from all substances, including those that had not effectively removed amyloid plaques and thus failed to secure regulatory approval. According to Dichter, the effectiveness of the approved drugs was evident in the outcomes observed among participants whose amyloid levels dropped significantly. Only those two antibodies achieved this outcome and received approval. The benefits of these new treatments extend beyond merely slowing the disease’s progression. For instance, Donanemab reduced the risk of deteriorating into severe dementia within 18 months by nearly half. This delay is crucial because it helps maintain patients' independence for longer periods. Initial feedback from treatment centers suggests that side effects such as cerebral edema or microhemorrhages occur less frequently than previously reported in clinical trials. Preliminary data after 36 months indicate that the buildup of amyloid-beta deposits resumes very slowly after treatment ends, suggesting that the therapeutic effects might persist even after discontinuation. Additionally, there is emerging evidence that the delay in disease progression continues to lengthen over time for both Lecanemab and Donanemab. While direct comparisons with placebo groups are no longer possible due to the design of the trials, external control groups suggest that the benefits could be more substantial than initially thought. Despite these advancements, Dichter acknowledged that the treatments can only slow the disease rather than halt it entirely. He explained that aging brains face multiple challenges beyond amyloid accumulation, including other harmful protein deposits and inflammatory processes. Nevertheless, he highlighted that these new therapies mark the first major progress in decades of Alzheimer’s research. By addressing one of the fundamental causes of the disease and successfully treating it, these drugs offer hope for future developments in the field.