Jagan Pillai, MD, PhD is a clinician-scientist who specializes in neurodegenerative conditions including Alzheimer’s disease. With the recent FDA approvals of lecanemab and donanemab, two groundbreaking monoclonal antibodies targeting β-amyloid proteins, the landscape of Alzheimer’s disease therapy is evolving rapidly. In this interview, Dr. Pillai discusses the lessons learned from these new medications, their differences, and the future of Alzheimer’s disease treatment.
WAM: What are the biggest lessons we have learned from using lecanemab?
Dr. Pillai: In July 2023, the FDA approved lecanemab for the treatment of mild Alzheimer’s disease. As with all new therapies, the jury is still out on real world effectiveness. One thing we know for certain, however, is that the more treatment options the better, allowing us to better tailor treatment to each patient. With options comes hope for patients and families that we will continue to find new ways to target and slow down the progression of Alzheimer’s disease.
That’s why we continue to engage in research—and monitor approvals of— monoclonal antibodies or anti-amyloid therapy targeting β-amyloid (Aβ), to treat Alzheimer’s disease.
WAM: What have we learned about managing the main side effect, ARIA?
Dr. Pillai: As with many medications, there are side effects. ARIA, or amyloid related imaging abnormalities, is one we closely monitor after infusion cycles to see how the patient is tolerating the medication. This is done through regular brain MRI scans. We’ve learned this requires much more in-depth engagement between the clinical team and patient as they go through these IV medications.
WAM: In July 2024, a second monoclonal antibody was approved for the treatment of mild Alzheimer’s: donanemab. What is the difference between lecanemab and donanemab?
Dr. Pillai: Both are part of a new class of medications for Alzheimer’s disease called anti-amyloid therapies. In research, both medications slowed down the progression of the disease in its early stages. From a patient’s perspective, a key difference is the frequency of infusions: lecanemab is biweekly, whereas donanemab is a monthly infusion.
Another difference is how the medications target amyloid, a protein that builds up in the brains of those with Alzheimer’s disease. Lecanemab removes amyloid proteins as they begin to form, whereas donanemab targets the amyloid after it has built up into plaque. For patients, this means donanemab could be stopped once the plaque has been lowered to a significant level.
The third difference is the frequency of potential side effects of lecanemab versus donanemab, notably serious adverse events occurred in 14.0% of the clinical trial participants on lecanemab and 17.4% on donanemab. That is why we monitor these medications to see how they’re tolerated over time.
The exciting thing is we now have an opportunity to choose the best treatment for each individual.
WAM: What is next in the Alzheimer’s treatment pipeline and why is continued participation in clinical research important?
Dr. Pillai: We have made progress with amyloid, now experimental therapies targeting tau, another hallmark protein of Alzheimer’s disease, are currently underway.
Continued participation in clinical research is crucial. We wouldn’t have lecanemab or donanemab without the people who were willing to be part of the clinical trials. It’s the only way for us to know if a new treatment is safe and effective.
Secondly, participation in research helps to increase our understanding of Alzheimer’s disease. Even when a trial does not lead to a new treatment, it can still provide valuable insights into how to better target the disease.