The Food and Drug Administration (FDA) recently gave full approval to Leqembi (lecanemab) for patients in the early stages of Alzheimer’s disease. Physicians and researchers at Washington University School of Medicine’s Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) in St. Louis were involved in the clinical trials evaluating Leqembi, in which they enrolled participants with the most common form of Alzheimer’s disease, which occurs in people age 65 and older.
Barbara Joy Snider, MD, PhD, a professor of neurology, led the trials at Washington University. Beginning in August, physicians at Washington University and BJC HealthCare will offer Leqembi to eligible patients. Those seeking more information about the drug and about who is eligible to receive it may call 314-362-WELL (9355).
Here, Snider answers questions about the drug.
Why is FDA approval of Leqembi such a big deal?
Leqembi doesn’t cure Alzheimer’s disease, and it can’t improve memory and thinking. It is, however, the first drug that has been shown to slow progression of Alzheimer’s disease in people with early-stage disease. A large clinical trial of Leqembi that Washington University’s Knight ADRC participated in showed that the drug slowed declines in memory and thinking by about 30% over the course of 18 months of treatment.
How does Leqembi work?
It targets the buildup of amyloid plaques in the brain, which are a hallmark of Alzheimer’s disease and may interfere with memory and thinking. The clinical trials indicate that Leqembi removes the amyloid plaques from the brain and that this, in turn, slows the progression of the disease.
Who is eligible to get the drug, and how is it given?
Leqembi is for people with mild Alzheimer’s disease, which means they have some problems with thinking and memory, but their symptoms aren’t severe. We don’t know if the drug will help people with more severe memory loss or cognitive problems, because the clinical trials only involved people with mild disease. The drug is given via IV infusions every two weeks at an infusion center.
Has some of the research here at Washington University helped make a drug such as Leqembi possible?
We have been doing Alzheimer’s disease research at the Knight ADRC for the last 40 years. Earlier studies done here, along with studies at other centers, have made the current drug trials possible. Overall, these earlier studies helped us develop the amyloid PET imaging scans, the blood tests and the spinal fluid tests, which make it possible to tell who has Alzheimer’s disease in people who have symptoms, such as memory loss and cognitive decline, and who is at higher risk of the disease prior to the onset of symptoms.
For many years now, we’ve also led a major international study of people who have inherited forms of Alzheimer’s disease, called the DIAN (Dominantly Inherited Alzheimer Network) study, which is funded largely by the National Institutes of Health (NIH). People enrolled in this study have inherited gene mutations that pretty much guarantee they will develop Alzheimer’s disease, typically in their 30s, 40s or 50s. The DIAN observational study is helping to define the natural history of Alzheimer’s in participants and establish reliable biomarkers that track progression of the disease.
The DIAN Trials Unit (DIAN-TU) is a treatment study evaluating whether it is possible to prevent or slow the onset of Alzheimer’s. This study is the first trial to evaluate a combination of two Alzheimer’s drugs: an amyloid drug, which is aimed at the amyloid plaques, as well as a drug that fights the buildup of the protein tau in the brain, which is closely linked to cognitive decline.
What percentage of Alzheimer’s patients might be eligible to receive the drug?
About 15% to 20% of all people with Alzheimer’s disease have mild symptoms and will be eligible for the drug. At Washington University, our neurology specialists at the Memory Diagnostic Center will be evaluating patients for their eligibility to receive the drug. We’re working with BJC HealthCare to make the drug available to patients, who will go to BJC infusion centers to receive it. Initially, it may be harder for people to get Leqembi if they live in rural or underserved communities and have limited access to specialty physicians and infusion centers. In addition, patients must have access to sophisticated brain imaging to check for side effects. We hope these issues will improve over time.
What are the side effects of Leqembi? And are they common?
Some people have a reaction to the infusion. That’s fairly common but usually very mild — things like feeling a bit anxious or short of breath, but usually that is short-lived. Although Leqembi generally has been shown to be safe, the clinical trials did reveal some potentially serious side effects. For example, small areas of the brain may get a little swollen as if they’re bruised. We also sometimes see areas with small amounts of bleeding, called microhemorrhages.
Collectively, these changes — which can be seen on brain scans — can happen in about 25% of people who receive Leqembi. In most cases, people taking the medication don’t even know this has happened because they don’t have any symptoms, and the brain bleeding or swelling resolves on its own. But a few patients can have more severe symptoms like headaches, confusion or even stroke-like symptoms. In very rare cases, the brain swelling or bleeding can be fatal. For this reason, the drug’s labeling includes a warning that the medication can cause serious and life-threatening events.
How much does Leqembi cost?
The drug is expected to cost $26,500 per year. Medicare has indicated that it will cover 80% of the cost of the medication, but there are other costs. Determining who is eligible may require sophisticated PET imaging scans, and those may not be covered by Medicare. There also are follow-up MRI scans that must be conducted once treatment begins to identify potential side effects. Covering 80% of the cost of the drug is helpful to patients, but there will be out-of-pocket costs, too.
We also don’t yet know how long a person will have to take the drug. In the clinical trial, people were on Leqembi for 18 months, but many of those in the trial are still taking the drug, and some of the findings seem to indicate that if people are on the drug longer, they do better. We’re continuing to get information about the effects of long-term treatment, which will help determine how long the drug will be helpful.
Is there any thought that a drug such as Leqembi might help prevent Alzheimer’s disease?
Yes. Our current knowledge suggests one of the first abnormalities that starts in someone on the path to developing Alzheimer’s disease symptoms is the aggregation of the amyloid protein into amyloid plaques in the brain. So, it’s possible that an anti-amyloid drug, such as Leqembi, given very early, before there are any memory problems, may be the most effective way to prevent things that happen later in the disease process, including the onset of memory problems and, ultimately, dementia.
The idea would be to prevent problems at the very onset of the disease, when amyloid pathology first is occurring, by treating with an anti-amyloid therapy that could, hopefully, prevent the whole process. There’s no evidence yet that Leqembi will do all of that, but that’s where new studies are heading. As an example, we are involved in the AHEAD study, which is evaluating Leqembi in people who are at risk of developing Alzheimer’s disease but do not yet have symptoms.
Listen to the School of Medicine podcast, “Show Me the Science,” for more of what WashU medicine neurologists have to say about Lequembi.
About Washington University School of Medicine
WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,800 faculty. Its National Institutes of Health (NIH) research funding portfolio is the third largest among U.S. medical schools, has grown 52% in the last six years, and, together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,800 faculty physicians practicing at 65 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.