What You Should Know About Lecanemab
Learn more about the new drug for Alzheimer’s disease, including who it may be appropriate for, risks, and benefits.
On Friday, January 6, 2023, the Food and Drug Administration announced its decision to grant accelerated approval to lecanemab for the treatment of Alzheimer’s disease.
Lecanemab, which will be marketed under the brand name Leqembi, is an anti-amyloid monoclonal antibody developed by Eisai and Biogen. This class of medications works by clearing amyloid deposits from the brain. Amyloid is a protein that accumulates in the brains of people with Alzheimer’s disease and is a critical element in the resulting dysfunction and damage to the brain.
Lecanemab is in the same class of therapies as aducanumab (also known by the brand name Aduhelm), which was approved by the FDA last year, but led to unprecedented controversy and eventually denial of coverage by the Centers for Medicare and Medicaid Services.
In the case of lecanemab, we still need to wait to see what CMS decides and whether coverage will be offered by Medicare or private insurance companies.
However, we are in a true inflexion point in the battle against Alzheimer’s disease. Compared with aducanumab and other prior medications in the same class, the results from the phase III clinical trial that led to the FDA approval of lecanemab show consistent and clinically demonstrable benefits in all the measures captured by the study. These are extremely important findings.
Dementia is the most feared health condition and Alzheimer’s is the most common cause of dementia, accounting for over 60% of cases. In 2019, over 50 million people were living with Alzheimer’s disease worldwide, and the number is expected to rise to over 150 million by 2050.
Lecanemab can become the first widely available disease-modifying therapy to slow the progression of Alzheimer’s, helping millions of people with mild cognitive impairment or mild Alzheimer’s dementia. And it is important to remember that lecanemab is likely only the first of a class of medications, using monoclonal antibodies targeting amyloid and other toxic proteins, to become available over the next few years with the potential to modify the course of Alzheimer’s and neurodegenerative diseases in general.
Can lecanemab 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. Lecanemab may help patients with dementia due to Alzheimer’s, but would not be helpful nor 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 lecanemab 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.
A careful neurological and neuropsychological evaluation to identify and characterize memory and cognitive difficulties is necessary to establish whether a patient might be helped by lecanemab. It’s also critical to determine the underlying brain pathology by looking for physical changes that signal Alzheimer’s disease.
Today, we use expensive positron emission tomography (PET) scans or a lumbar puncture to obtain and analyze the cerebrospinal fluid for the levels of amyloid and tau proteins. The presence of these proteins indicates a diagnosis of Alzheimer’s disease. In the future, blood tests will become available for clinical use and be combined with reliable markers of cognitive performance to offer scalable, efficient, and inexpensive screening.
How much benefit can I expect from lecanemab?
The results of lecanemab’s phase III trial – known as Clarity AD – demonstrate a slowing of the progression of Alzheimer’s by about 30%. This clinical benefit is important, but only moderate. By way of analogy, if a patient’s decline is compared to a car speeding down the street at 70 mph, lecanemab can slow the decline to the equivalent of 50 mph – still plenty fast. Overall, the benefits represented a modest improvement, which may have little impact on day to day function. There is clearly a long way to go to truly stop progression of the disease.
For reasons that aren’t yet clear, the Clarity AD trial showed much stronger benefits for men than women. There were no real differences in risk of side effects.
In addition, it is important to understand that even though the benefits demonstrated by the Clarity AD trial were statistically significant, they varied substantially from patient to patient. That’s why it’s essential to consider each individual’s circumstances to decide whether lecanemab is appropriate. The clinical benefit is important, but only moderate, and it needs to be carefully balanced against the risk of side effects and complications for each patient.
Is lecanemab safe?
Patients with Alzheimer’s disease often have other illnesses. Fortunately, the Clarity AD trial included patients with several other conditions. This means the results can be used to assess the likely benefit but also the potential risks of lecanemab for a given individual patient.
For instance, significant numbers of patients were included with hypertension, diabetes, heart disease, high blood cholesterol, obesity, and even a small number on blood-thinning medication. Most patients tolerated lecanemab well despite other conditions they had, but those on blood-thinning medications – known as anticoagulants – showed an increased risk for bleeds in the brain, even serious ones which have led to the death of three patients so far.
Overall, nearly 30% of patients developed a brain complication called “amyloid-related imaging abnormality” (ARIA), which can involve inflammation, swelling, and risk of bleeding in the brain. In nearly 4% of the patients this was associated with serious symptoms. That’s why it’s essential to obtain a brain magnetic resonance image, or MRI, before starting the treatment with lecanemab. MRIs should be repeated every few months during treatment to ensure there are no signs of small bleeds or brain inflammation which could get worse and lead to serious consequences.
Furthermore, lecanemab needs to be given as an intravenous infusion and reactions to the infusions – such as pain, fever, nausea, or chills – occurred in 26% of participants. These were generally mild reactions, but some individuals can have stronger allergic reactions requiring treatment and even hospitalization.
With all this in mind, the potential benefits of lecanemab need to be considered in the context of its risks. If you’re considering the treatment, it’s important to undergo a careful assessment and to discuss your own individual risks and benefits with your physician.
What does lecanemab cost? Is it covered by insurance?
The Centers for Medicare and Medicaid Services has not yet made a decision about whether they will cover lecanemab. Many private insurers follow the lead of CMS. This decision may not be made for several months, or potentially later in 2023 if CMS decides to wait to review additional data on safety and effectiveness.
So far, we know that the cost of lecanemab will be $26,500 per year. That may not include the cost of the intravenous infusions required every two weeks to receive the treatment, and it does not account for the cost of diagnosis, administration of the drug, and monitoring. For example, there’s no information yet on whether the MRI scans required every two months would be covered by insurance.
Until CMS makes its decision, lecanemab will only be available to those who are able and willing to pay out-of-pocket for the drug and the associated costs. This raises important questions about equal access to the drug.
Should lecanemab be taken alone or combined with other treatments for Alzheimer’s?
While the approval of lecanemab opens the door to a new class of treatments for Alzheimer’s disease, it 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 should be considered as one part of a comprehensive strategy. There are also other medications that 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 up to 40% of dementia cases may be prevented or delayed by making changes to modifiable lifestyle factors, including quitting smoking and cutting back on excessive alcohol use.
Medication and lifestyle changes are beneficial on their own and offer the potential to maximize the benefits of lecanemab.
When should lecanemab be started?
To maximize the benefits of lecanemab, it’s important 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 been ongoing generally for over a decade.
Ideally, early detection would require screening, like what is routinely done for various forms of cancer. However, most screening and diagnosis today is dependent 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 represents a loss of valuable time for treatments such as lecanemab. Dementia already disproportionately affects Black Americans, Hispanic Americans, Asian Americans, and American Indian/Alaska Natives, among others, so these barriers to treatment and delays in accessing care could exacerbate existing disparities. Primary care providers need to be empowered to conduct adequate screening to ensure timely assessments and care.
To achieve this goal, primary care practices at Hebrew SeniorLife and specialists at the Deanna and Sidney Wolk Center for Memory Health in Boston are working together to offer efficient care pathways to implement interventions as early as possible. The Wolk Center 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.
How can I get lecanemab?
For now, if you are interested in considering lecanemab, you should talk with your primary care provider and see a dementia specialist for a detailed assessment and specific diagnosis. The Wolk Center for Memory Health has established a specific accelerated evaluation path for patients who may want to consider lecanemab. Hebrew SeniorLife is currently evaluating our ability to offer lecanemab on-site, including protocols for ongoing monitoring of patients undergoing treatment.
Concerned about signs of memory loss? We’re here to help.
At the Deanna and Sidney Wolk Center for Memory Health in Boston, 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 prevention of cognitive decline, early diagnosis, specific subtype diagnosis, ongoing care for managing dementia, and more.
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, we’d love to hear from you. Call us at 617-363-8600 or contact the Wolk Center online.
The Deanna and Sidney Wolk Center for Memory Health at Hebrew SeniorLife provides outpatient memory care services, in person and virtually, for people living with cognitive symptoms — and for their families and caregivers.