FDA Approves New Alzheimer’s Treatment: What to know About Leqembi® (lecanemab)

Leqembi® (lecanemab) was approved to treat Alzheimer’s disease in January, 2023 under the FDA’s Accelerated Approval process for diseases with an unmet need for treatment.¹ The manufacturers, Eisai pharmaceuticals, plan to submit data for full FDA approval by the end of March 2023.

Here, we answer some common questions about Leqembi and summarize what is known about its safety and effectiveness. Patients and their families should speak with their physician and weigh the potential benefits and risks before deciding whether to seek treatment with Leqembi.

what is leqembi and how does it work?

Leqembi is a monoclonal antibody approved for the treatment of Alzheimer’s disease in patients with mild cognitive impairment or mild dementia. It is administered intravenously every two weeks and takes about one hour to receive each dose.²

Leqembi works by targeting a peptide called amyloid-beta (Aβ), which is known to build up and form plaques in the brains of patients with Alzheimer’s disease.³ Leqembi binds to and eliminates the Aβ fibers that aggregate to form those plaques. Researchers believe that medications that reduce the formation of Aβ plaques may mitigate the symptoms of Alzheimer’s and slow the progression of the disease.

what is the evidence that leqembi is effective in treating alzheimer’s diesase?

In a large clinical trial, patients treated with Leqembi had a 70% reduction in Aβ plaques after 79 weeks of treatment, as measured by PET scan, while patients who did not receive treatment had slight increases in Aβ plaques.³

Analysis of Alzheimer’s symptoms showed more modest improvement.³ The rate at which symptoms progressed was 27% slower in patients treated with Leqembi than in those who were not treated. Symptoms were analyzed by a common scale for cognition, including measures of memory, judgement, and problem solving. During the 18-month study, scores for patients treated with Leqembi worsened at a rate of 0.45 points slower than patients who were not treated. Based on this rate, models suggest that symptom progression in Leqembi-treated patients may take 7.5 months longer than progression in patients who were not treated, over the course of 30 months. While these results were not robust, there are limited treatment options despite decades of research. These modest gains provide hope for patients with few other options and pave the way for better treatments in the future.

Is Leqembi a cure for alzheimer’s disease?

Leqembi is not a cure for Alzheimer’s disease. The goal of treatment is to slow down the progression of the disease.

Does Leqembi reverse existing memory loss or impairment?

There is no evidence that Leqembi can reverse existing memory loss or cognitive impairment caused by Alzheimer’s disease.

What are the side effects of leqembi and are there any serious risks?

About 27% of patients experienced mild infusion-related side effects, such as flu-like symptoms, nausea, vomiting, and headaches.

Leqembi was also associated with the development of irregularities observed on brain MRIs, called amyloid-related imaging abnormalities (ARIA). These included brain swelling or leaking of fluid in the brain in 13% of Leqembi-treated patients as compared with 2% in patients who were not treated. Bleeding in the brain was observed in about 17% of treated patients compared with 9% of untreated patients. ARIA has also been reported in other treatments that target Aβ, like Aduhelm (aducanumab).⁴

In addition, three patients taking Leqembi died from complications involving brain bleeding or seizures.⁵ Two of these patients had underlying conditions that were being treated with medications to prevent blood clots, which may have worsened any bleeding caused by Leqembi.

To monitor patients for ARIA, three MRI scans during the first 14 weeks of treatment with Leqembi are required.²

What is known about who may benefit most from treatment with leqembi?

Leqembi has only been tested in patients with mild cognitive impairment or mild dementia. It has not been studied in patients with more advanced disease. Prior to treatment with Leqembi, the physician must confirm the presence of Aβ plaques in the patient.² Tests for  plaques include Aβ PET scan and lumbar puncture.

Patients who had two copies of a gene calledapolipoprotein E4 (APOE4) were less likely to benefit from Leqembi treatment and were more likely to be at risk of ARIA. APOE4 is a gene that predisposes patients to developing Alzheimer’s, but it is not commonly screened for by doctors. Patients may wish to consider APOE4 genetic testing prior to seeking treatment with Leqembi to help inform treatment decisions and disease management.

How much does Leqembi cost and will it be covered by Medicare?

Leqembi will be listed at $26,500 per year. The Centers for Medicare and Medicaid Services (CMS), which oversees Medicare, has issued a statement that currently denies coverage to all antibody treatments against Aβ (i.e., Leqembi and Aduhelm). This decision was made in response to the FDA approval of Aduhelm in 2021, despite safety risks and limited efficacy. As a result, insurance coverage will initially be limited. CMS has stated that broader coverage will be provided if Leqembi receives full FDA approval, allowing coverage for more patients.

References

1. Commissioner, O. of the. FDA Grants Accelerated Approval for Alzheimer’s Disease Treatment. FDA https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-disease-treatment (2023).
2. Eisai Pharmaceuticals. Prescribing-Information.pdf. Leqembi Prescribing Information https://www.leqembi.com/-/media/Files/Leqembi/Prescribing-Information.pdf?hash=3d7bf1a2-5db2-4990-8388-81086f415676.
3. van Dyck, C. H. et al. Lecanemab in Early Alzheimer’s Disease. N Engl J Med 388, 9–21 (2023).
4. Salloway, S. et al. Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease. JAMA Neurology 79, 13–21 (2022).
5. Scientists tie third clinical trial death to experimental Alzheimer’s drug | Science | AAAS. https://www.science.org/content/article/scientists-tie-third-clinical-trial-death-experimental-alzheimer-s-drug.