What You Should Know About Lecanemab and Donanemab for Alzheimer’s Disease

For many individuals and families affected by Alzheimer’s, Food and Drug Administration approvals in 2023 and 2024 introduced new and meaningful treatment options. In July 2023, the FDA granted full approval for lecanemab for the treatment of early, symptomatic Alzheimer’s disease. In July 2024, it granted full approval for donanemab for the same indication.

In large controlled studies, both lecanemab and donanemab have been shown to slow the progression of Alzheimer’s disease. Lecanemab is marketed under the brand name Leqembi, while donanemab is marketed under the brand name Kisunla.

This blog post answers the questions we hear most often about these newer medications at the Deanna and Sidney Wolk Center for Memory Health and what they mean for people living with Alzheimer’s disease-related dementia. 

What are lecanemab and donanemab? 

Lecanemab and donanemab are disease-modifying therapies in the class of anti-amyloid monoclonal antibodies. These antibodies work by clearing amyloid deposits from the brain. Amyloid plaques are a type of protein that builds up in the brains of people with Alzheimer’s disease, causing cell damage and disruption. 

We are at a true inflection point in the fight against Alzheimer’s disease. Compared with earlier medications in the same class, the results from phase III clinical trials that led to FDA approval of lecanemab and donanemab show consistent, meaningful benefits across multiple measures of disease progression. These are extremely important findings for treating Alzheimer’s.

Can lecanemab or donanemab help me or my loved one?

Alzheimer’s disease is the most common cause of dementia, but it’s important to remember that not all patients with dementia have Alzheimer’s disease. Lecanemab and donanemab may help patients with dementia due to Alzheimer’s, but would not be helpful or indicated for patients with dementia due to other causes. Therefore, it’s critical to undergo the appropriate evaluation to establish the specific diagnosis of Alzheimer’s disease.

In addition, patients likely to benefit from these medications are those with mild cognitive impairment or early dementia. Those with more advanced disease and greater cognitive impairment are likely not good candidates for the treatment. Around 90% of patients are not diagnosed at the mild cognitive impairment or early dementia stage. That means that by the time of diagnosis, it could be too late to benefit from these medications.

However, an early diagnosis can change that. Dementia typically starts as mild cognitive impairment, a measurable decline in at least one cognitive domain that does not yet impact activities of daily living. It is possible for mild cognitive impairment to never progress to dementia.  

If you are concerned about cognitive decline, a detailed evaluation is critical to accurately assess your symptoms. Even without noticeable concerns, annual assessments can guide early interventions and potentially delay or prevent dementia. 

A careful neurological and neuropsychological evaluation is needed to establish whether someone may benefit from these drugs. Doctors also look for physical changes in the brain that signal Alzheimer’s disease. 

Newly approved blood tests can help identify these changes before pursuing more invasive testing, such as PET scans or lumbar punctures. In addition, a brain MRI to rule out small brain bleeds, a medication review, and specific blood tests, including determining APOE genetic type, are essential to assess your risk before starting these medications.

Some people are not candidates for lecanemab or donanemab because they pose an excessive risk for them. It is critical to carefully assess the potential benefits for each individual and balance them against the possible risks.

How much benefit can I expect from lecanemab or donanemab?

The results of lecanemab’s phase III trial demonstrate a slowing of the progression of Alzheimer’s by about 30%. The results of donanemab’s phase III trial are similar. Longer follow-up studies of patients with sustained treatment show promising findings suggesting a growing benefit.

These clinical benefits are important, but only moderate. One way to think about these medications is that they can slow, but not stop, cognitive decline. If a patient’s decline is compared to a car speeding down the street at 70 miles per hour, lecanemab or donanemab can slow the decline to the equivalent of 50 miles per hour. Overall, the benefits represent a modest improvement, which may have little impact on day-to-day function. There is clearly a long way to go to truly stop the progression of the disease. 

While the benefits demonstrated in the trials were statistically significant, they varied substantially from patient to patient. That’s why it’s essential to consider each individual’s circumstances, weighing potential benefits against possible risks, to decide whether lecanemab or donanemab is appropriate.

For example, for reasons that aren’t yet clear, the lecanemab phase III trial showed much stronger benefits for men than women. There were no real differences in risk of side effects. For women, donanemab might be a better option.

Another consideration is that both medications are given by infusion at a specialized center. Lecanemab currently requires an infusion every two weeks, while donanemab requires one infusion per month. However, an oral form of lecanemab has just been approved, meaning the requirement of infusions is likely to change in the near future.
In addition, both treatments require regular brain MRIs before treatment begins and between infusions to monitor for potential side effects, including small bleeds or brain inflammation, and to maximize safety. Because of this monitoring, these therapies require an ongoing time commitment. 

Are these medications safe?

People with Alzheimer’s disease often have other health conditions. The clinical trials that led to the approval of lecanemab and donanemab included people with several other conditions, including hypertension, diabetes, heart disease, high cholesterol, obesity, and a small number who were taking blood-thinning medications.

Overall, most patients tolerated the medications well despite other health conditions. Some individuals, particularly those on blood-thinning medications known as anticoagulants, had a higher risk of potentially serious brain bleeding. A recent blog post by Darae Ko, MD, MSc, examines what to consider when combining lecanemab or donanemab with blood thinners. 

Additionally, when these medications are given as intravenous infusion up to 30% of patients experience infusion-related reactions, including pain, fever, nausea, or chills. While most reactions are mild and manageable, some individuals can have stronger allergic reactions requiring treatment and even hospitalization.

As with any treatment, the potential benefits of lecanemab or donanemab need to be weighed against their risks. Careful evaluation, ongoing monitoring, and open conversations with your physician can help ensure you make a thoughtful, informed treatment decision. At the Wolk Center for Memory Health, we have established a careful process to help you and your family consider all pertinent factors and reach the best decision for you.

Do I qualify for donanemab or lecanemab? 

The Centers for Medicare & Medicaid Services has approved Medicare coverage for lecanemab and donanemab.

To receive Medicare coverage, you need to: 

1. Be enrolled in Medicare
2. Be diagnosed with mild cognitive impairment or early dementia due to Alzheimer’s disease, with a level of cognitive functioning that meets treatment criteria 
3. Have documented evidence on a PET scan of beta-amyloid plaque in the brain
4. Have no significant risk factors that would make treatment unsafe 
5. Receive care from a physician participating in a qualifying registry 

Many private insurers follow CMS’s lead in offering coverage.

What does lecanemab cost? Does insurance cover it?

Treatment with lecanemab or donanemab is expensive. It involves not only the cost of the intravenous infusions but also the need for regular brain MRIs, neurological evaluations, and monitoring. 

Fortunately, most insurance companies cover all costs for appropriate candidates who complete detailed evaluations and meet specific inclusion criteria. 

Should lecanemab or donanemab be combined with other Alzheimer’s treatments?

While the approval of lecanemab and donanemab opens the door to a new class of treatments for Alzheimer’s disease, they shouldn’t be considered the sole treatment or the silver bullet. 

For individuals with Alzheimer’s who are exhibiting memory difficulties and cognitive symptoms, lecanemab or donanemab should be considered as one part of a comprehensive treatment strategy. Other medications can be used, including some to improve metabolic dysfunctions, prevent brain irritation or inflammation, and control diabetes or hypertension if necessary. 

Lifestyle modifications and better control of cardiovascular risk factors can also be part of treatment. In fact, there’s strong scientific evidence that nearly 45% of dementia cases may be prevented or delayed by making changes to modifiable lifestyle factors, regular physical activity, balanced nutrition, quality sleep, social connection, and stress management. 

If you’re not sure where to start, the Wolk Center for Memory Health’s Evergreen Brain Health Coaching helps people focus on modifiable lifestyle factors through personalized, practical guidance in individual and small-group coaching settings, empowering you to take an active role in protecting and strengthening your brain health at any age. Learn more about our brain health coaching program. 

When should these medications be started?

To maximize the benefits, it’s crucial to begin treatment as early as possible. However, the current approach to dementia diagnosis and care is largely reactive, considered only when patients or families raise concerns. We know that by the time a person receives an Alzheimer’s diagnosis, the illness has likely been ongoing for over a decade. 

Ideally, early detection would require screening, like what is routine for various forms of cancer. However, most screening and diagnosis today depend on specialists like neurologists or geriatric psychiatrists, and it’s not uncommon to wait six to nine months for an appointment due to a shortage of specialists. This delay represents a loss of valuable time for treatments such as lecanemab or donanemab. 

To close this gap, the primary care practices at Hebrew SeniorLife and specialists at the Wolk Center for Memory Health are working together to offer efficient care pathways to implement interventions as early as possible. The Wolk Center for Memory Health offers brain screening assessments to identify individuals with cognitive decline as early as possible, before they exhibit any symptoms, and enable early interventions if indicated.

Exploring treatment options for Alzheimer’s disease? 

If you are considering lecanemab or donanemab, talk with your primary care provider and see a dementia specialist for a detailed assessment and a specific diagnosis. 

At the Wolk Center for Memory Health, we offer care for those who are concerned about possible memory loss, for seniors with Alzheimer’s disease and other forms of dementia, and for family members caring for a loved one with memory loss. 

We specialize in preventing cognitive decline, early diagnosis, specific subtype diagnosis, ongoing care for managing dementia, and more. For patients considering lecanemab or donanemab, we offer an accelerated evaluation pathway, along with established protocols for evaluation and ongoing monitoring during treatment. 

If you’d like to schedule a visit for a memory assessment, treatment, or family support, or you’re wondering if you’re a candidate for lecanemab or donanemab, we’d love to hear from you. Call us at 617-363-8600 or contact the Wolk Center for Memory Health online.

Nicholas Vogt, MD, PhD, also contributed to this blog post.