What is the efficacy of Leqembi (lecanemab) for Alzheimer's disease dementia?

From the Guidelines

Leqembi (lecanemab) is a moderately effective treatment for early Alzheimer's disease, showing a significant slowing of cognitive decline compared to placebo in clinical trials, as reported in recent studies 1, 2. The medication is administered as an intravenous infusion every two weeks at a dose of 10 mg/kg. Patients typically see modest benefits in memory, thinking, and daily functioning, with the most significant effects observed when treatment begins in early stages of the disease.

Key Points to Consider

• Leqembi works by targeting and removing amyloid beta plaques in the brain, which are believed to contribute to Alzheimer's progression.
• However, the medication comes with potential serious side effects, including brain swelling (ARIA-E) and small brain bleeds (ARIA-H) that occur in about 21% of patients.
• Regular MRI monitoring is required during treatment, especially in the first months.
• Leqembi does not cure Alzheimer's or reverse existing damage but may help slow the disease progression for a period of time.
• The medication is most appropriate for patients with mild cognitive impairment or early Alzheimer's disease who have confirmed amyloid plaques through testing, as emphasized by recent recommendations for clinical implementation of blood-based biomarkers for Alzheimer's disease 2.

Clinical Implementation

• Biomarker testing to determine the presence of amyloid pathology is likely to become an essential component of the routine assessment of people who present for evaluation of cognitive impairment, as noted in a recent consensus statement 1.
• Blood biomarker tests for the detection of AD pathology have been developed and are now widely used in AD research studies and clinical trials, offering a more acceptable and accessible alternative to amyloid PET and CSF tests 1.

From the FDA Drug Label

The primary endpoint was change from baseline on a weighted composite score consisting of selected items from the Clinical Dementia Rating scale Sum of Boxes (CDR-SB), MMSE, and Alzheimer Disease Assessment Scale – Cognitive Subscale 14 (ADAS-Cog14) at Week 53 LEQEMBI had a 64% likelihood of 25% or greater slowing of progression on the primary endpoint relative to placebo at Week 53, which did not meet the prespecified success criterion of 80%. Key secondary efficacy endpoints included the change from baseline in amyloid PET SUVR composite at Week 79 and change from baseline in the CDR-SB and ADAS-Cog14 at Week 79

The effectiveness of LEQEMBI for Alzheimer's dementia is supported by clinical trials, with a 64% likelihood of 25% or greater slowing of progression on the primary endpoint relative to placebo at Week 53 3. However, this did not meet the prespecified success criterion of 80%.

• Primary endpoint: change from baseline on a weighted composite score consisting of selected items from the Clinical Dementia Rating scale Sum of Boxes (CDR-SB), MMSE, and Alzheimer Disease Assessment Scale – Cognitive Subscale 14 (ADAS-Cog14) at Week 53
• Key secondary efficacy endpoints: + change from baseline in amyloid PET SUVR composite at Week 79 + change from baseline in the CDR-SB and ADAS-Cog14 at Week 79 It is indicated for the treatment of Alzheimer’s disease, and treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease 4.

From the Research

Efficacy of Leqembi for Alzheimer's Dementia

• Leqembi (lecanemab) has been approved in the United States for the treatment of Alzheimer's disease (AD) to be initiated in early AD with confirmed brain amyloid pathology 5.
• Clinical trials have shown that lecanemab reduces amyloid in the brain and slows cognitive decline 6, 7.
• However, one study found that lecanemab did not slow cognitive decline in women and APOE4 carriers, and even enhanced the decline in study participants with 2 APOE4 genes 6.
• A systematic review of clinical trials found that lecanemab was efficacious in reducing the accumulation of beta-amyloid and slowing down the cognitive decline, and was well tolerated 7.

Safety and Side Effects

• Adverse events may occur with lecanemab, including amyloid-related imaging abnormalities (ARIA) and infusion reactions 5, 8.
• ARIA can be asymptomatic, but a few cases are serious or, very rarely, fatal 5.
• Microhemorrhages and rare macrohemorrhages may occur in patients receiving lecanemab, and anticoagulation increases the risk of hemorrhage 5.
• The most common treatment-emergent adverse events were headache, infusion-related reactions, and ARIA-edema 7.

Administration and Monitoring

• Administration of lecanemab at clinical trial sites by individuals experienced with monoclonal antibody therapy differs from community clinic-based administration 5.
• Clinician and institutional preparedness are mandatory for use of lecanemab, and protocols for management of serious events should be developed and implemented 5.
• Patients and their care partners must understand the potential benefits, the potential harms, and the monitoring requirements for treatment with lecanemab 5.
• An assessment and educational framework is necessary for medical staff to use in their practice when administering anti-amyloid immunotherapies like lecanemab 8.