Lecanemab Considerations and Efficacy

In light of lecanemab-IRMB's approval from the Food and Drug Administration (FDA) for early Alzheimer disease treatment, Psych Congress Network met virtually with Paul Schulz, MD, a neurologist at the University of Texas Health Science Center, Houston, Texas, to discuss this new drug, risks and benefits, and efficacy information. Dr Schulz discusses the importance of monitoring patients during phase 4 trials and emphasizes the importance of physical exams, blood work, and EKGs in identifying unexpected problems. 

Regarding drug efficacy, Dr Schulz explains that while these medications don't offer a cure, they have shown promising results. All 3 anti-amyloid therapies (aducanumab, lecanemab, donanemab) slow the progression of activities of daily living by 40%, providing relief to patients and their caregivers. While not a complete solution, these therapies offer hope and highlight the need for continuous monitoring and exploration of further treatment options, Dr Schulz says.

Catch up on part 1: Advantages and Drawbacks of Lecanemab in Alzheimer Disease Treatment 

Catch up on part 2: Patient Considerations When Prescribing Lecanemab for Alzheimer Disease

Read the Transcript:

Psych Congress Network: How would you recommend clinicians balance the risk and benefits when making treatment decisions?

Dr Paul Schulz: The way I look at phase 4 is the same as phase 1, 2, and 3, and that is that I monitored a lot of things during those phases to make sure that the medication was safe. And my thought is to continue to do the same thing in phase 4 until we're all comfortable with the fact that there aren't any unanticipated challenges, problems, et cetera, interactions with medications or diseases that our clients have. So in all of our anti-amyloid therapy trials, we do MRIs regularly to look for ARIA-E and H because again, three-quarters of people don't have any symptoms of that, and we want to detect those. So MRIs are going to be a really important part of giving these medications and therapy. Physical exams will be very important. Every time I see a patient and give the drug, I examine them first to make sure they don't have a focal finding that might suggest that they already have ARIA going on. And in that case, I stop and don't give them the infusion, I send them for an MRI to see what's going on.

Also, during our trials, we do a lot of blood work because we don't know if any of these drugs are going to affect the liver, the kidneys, the heart, et cetera, and we do EKGs. So blood work and EKGs we do regularly to make sure that there's no unanticipated problem. So if you have someone though with early renal disease, for example, you'd especially want to do monitoring of blood work to make sure that the antibodies that we're giving don't have some unanticipated effect on our patients.

And another really important point in all of our trials is that we give a lot of questionnaires about how a person's feeling and responding not only to the disease, but also to the therapy that we're giving them. As an example, I don't want to be morbid, but asking people about suicidality is a really critical item that we do regularly because, as all of you who take care of people with Alzheimer's know, it's a very distressing disease. People are losing function, they're losing memory, it's affecting their real lives. They're going backwards, so to speak, in their activities of daily living and it's very annoying and distressing. So asking people or giving them a suicidality questionnaire, giving them a depression questionnaire, an anxiety questionnaire, probably a very good idea so that they can say things freely in writing that we can read. They don't have to say it out loud in front of their loved ones, and we can monitor them that way.

The main point I'm making going forward is that because this is the first time we're going to give it to people with other diseases, I think it's going to be really important to do the MRIs, the blood work, the physical exams, the EKGs and the questionnaires to make sure that we don't find anything unanticipated as we roll this out to the rest of the community. But hopefully we'll have nothing but good news. This is an exciting time for Alzheimer's disease to finally have something that works and that made it through the FDA. And so hopefully we have good news with our patients doing better, but I think part of that will be monitoring them to make sure we don't have any unanticipated side effects with these medications.

PCN: What is the degree of efficacy of these drugs? 

Dr Schulz: The drugs are the first time we've seen a response, which is absolutely fabulous, but I want to set people's expectations that we haven't figured out how to cure yet. Hopefully around the road to that. But right now what happens is, like with lecanemab, it slows things cognitively about 25%. Slowing it 100% would mean you cured it. 25% means that we buy, people say five months in a year and a half, they're that much better than they would be otherwise.

There are other aspects of the outcomes though that have been even more positive. So for example, one of the really awful things that happens to people with Alzheimer's disease, even at the MCI stage, is they start losing activities of daily living, making a sandwich, paying their bills, driving their car, operating their remote control. It turns out that all three of the anti-amyloid therapies aducanumab, lecanemab, donanemab, they slow the progression of ADLs by 40%, so it's just under halfway. So that's a very significant preservation of something that really annoys patients and their families, which is the loss of ADLs.

And for the first drug, aducanumab, they also measured outcomes in terms of what we call neuropsychiatric symptoms. That means agitation, aggression, hallucinations, delusions. Those are really, really distressing to patients and their loved ones. As you can imagine, if your loved one is distressed with a hallucination of someone trying to kill the family or steal from them, it would be awful for the patient and for you. Aducanumab slowed the progression of that over a year and a half by 87%. So it really put the brakes on that. So again, about 25 to 35% cognitive slowing by the three meds, all three of them slow ADL progression 40% and the one drug where the neuropsychiatric symptoms were measured, it was 87%. So again, not a cure, but a cause for hope. And my thought is to have people on these medicines while we keep looking for other medicines, and hopefully we will be adding something down the road that has even better efficacy.

Paul Schulz, MD, is a professor of neurology at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth). He received his combined BA-MD degrees from Boston University in 1984. He did a medical internship there, and moved to Baylor College of Medicine for his residency in Neurology. He stayed for a laboratory fellowship in cellular neurophysiology after which he became an assistant professor. Later, he was an associate professor of neurology, neuroscience, and translational biology and molecular medicine. Dr. Schulz was also the vice chair of education for neurology, the deputy chair of the Methodist neurology service, and directed the Cognitive Disorders Clinics at Baylor and the Houston Veterans Administration Hospital.