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

From the Guidelines

Leqembi (lecanemab) has been shown to be effective in slowing cognitive decline in patients with prodromal Alzheimer's disease, with clinical trials demonstrating a 27% reduction in cognitive decline compared to placebo over 18 months 1.

Key Points to Consider

• The medication works by targeting and removing amyloid beta plaques in the brain, which are believed to contribute to Alzheimer's disease progression.
• Treatment with Leqembi should be initiated by healthcare providers experienced in diagnosing and treating Alzheimer's disease.
• Before starting treatment, patients need baseline MRI screening to check for brain abnormalities, and regular MRI monitoring during treatment to watch for amyloid-related imaging abnormalities (ARIA).
• Common side effects include infusion-related reactions, headache, and ARIA.

Clinical Context

The use of Leqembi in prodromal Alzheimer's disease is supported by recent studies, including a Consensus Statement from The Global CEO Initiative (CEOi) on Alzheimer’s Disease BBM Workgroup, which highlights the importance of accurate biomarker-based diagnosis of AD in people with mild cognitive impairment (MCI) and mild dementia 1.

Recommendations for Use

• Leqembi should be considered for patients with prodromal Alzheimer's disease who have biomarker confirmation of amyloid pathology.
• Treatment should be initiated early in the disease course, specifically during the mild cognitive impairment or early dementia stages when amyloid plaques are present but before extensive neurodegeneration has occurred.
• Healthcare providers should carefully monitor patients for potential side effects and adjust treatment as needed.

From the FDA Drug Label

The efficacy of LEQEMBI was evaluated in two double-blind, placebo-controlled, parallel-group, randomized studies (Study 1, NCT01767311; Study 2 NCT03887455) in patients with Alzheimer’s disease (patients with confirmed presence of amyloid pathology and mild cognitive impairment [64% of patients in Study 1; 62% of patients in Study 2] or mild dementia stage of disease [36% of patients in Study 1; 38% of patients in Study 2], consistent with Stage 3 and Stage 4 Alzheimer’s disease). In both studies, patients were enrolled with a Clinical Dementia Rating (CDR) global score of 0.5 or 1.0 and a Memory Box score of 0. 5 or greater. 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 efficacy of Leqembi (lecanemab) for prodromal Alzheimer's disease is not directly addressed in the provided drug label, as the studies described enrolled patients with mild cognitive impairment or mild dementia stage of disease, consistent with Stage 3 and Stage 4 Alzheimer’s disease. However, the label does mention that 64% of patients in Study 1 and 62% of patients in Study 2 had mild cognitive impairment, which can be considered a prodromal stage of Alzheimer's disease.

• The primary endpoint of the study did not meet the prespecified success criterion of 80%.
• Key findings include a 64% likelihood of 25% or greater slowing of progression on the primary endpoint relative to placebo at Week 53.
• Secondary endpoints showed changes from baseline in amyloid PET SUVR composite and cognitive scales at Week 79. However, the FDA label does not provide a clear answer to the question of Leqembi's efficacy for prodromal Alzheimer's disease, as the term "prodromal" is not explicitly mentioned in the context of the study results 2.

From the Research

Efficacy of Leqembi (lecanemab) for Prodromal Alzheimer's Disease

• The efficacy of Leqembi (lecanemab) for prodromal Alzheimer's disease is supported by clinical trial data, as stated in the Appropriate Use Recommendations 3.
• Lecanemab is approved in the United States for the treatment of Alzheimer's disease to be initiated in early AD with confirmed brain amyloid pathology 3.
• The safety and efficacy of lecanemab are known only for patients like those participating in the phase 2 and phase 3 lecanemab trials 3.
• Adverse events may occur with lecanemab, including amyloid-related imaging abnormalities (ARIA) and infusion reactions 3.
• Patients who are apolipoprotein E ε4 (APOE4) gene carriers, especially APOE4 homozygotes, are at higher risk for ARIA 3.

Comparison with Other Treatments

• Other studies have investigated the efficacy of different treatments for Alzheimer's disease, such as candesartan 4, memantine, donepezil, and rivastigmine 5, 6, 7.
• These studies suggest that these treatments may have benefits in reducing cognitive decline and improving functional outcomes in patients with Alzheimer's disease 4, 5, 6, 7.
• However, the efficacy of lecanemab specifically for prodromal Alzheimer's disease is not directly compared to these other treatments in the provided evidence.

Safety and Monitoring

• The Appropriate Use Recommendations for lecanemab emphasize the importance of monitoring for adverse events, such as ARIA and infusion reactions 3.
• Patients requiring anticoagulants should not receive lecanemab until more data regarding this interaction are available 3.
• APOE genotyping is recommended to better inform risk discussions with patients who are lecanemab candidates 3.