Regulatory Decision Summary for Leqembi

The purpose of this New Drug Submission (NDS) is to seek market authorization for Leqembi (lecanemab) as a disease-modifying treatment in adult patients with Alzheimer’s disease. Treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of the disease. Following review, the recommended indication has been restricted to patients who are apolipoprotein E ε4 (ApoE ε4) noncarriers or heterozygotes, and who have confirmed amyloid pathology.

Based on the review of the data provided in this NDS, Health Canada issued a Notice of Compliance with Conditions - Qualifying Notice (NOCc-QN) on October 3, 2025. In their response to the NOCc-QN, the sponsor provided a “Letter of Agreement” on October 6, 2025 and a “Letter of Undertaking” on October 14, 2025 which were both considered acceptable.

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

One pivotal (Study 301) phase 3, placebo-controlled, double-blind, parallel-group, 18-month study conducted in patients aged 50-90 years old with early Alzheimer’s disease (AD) was provided in this submission for Leqembi (lecanemab). A Notice of Non-Compliance (NON) was issued to the company in March 2024 requesting they address the limited therapeutic benefit (clinical efficacy) and the identified safety risks of the product. In the response to the NON, the company provided post hoc efficacy analyses of the initial data which suggested that treatment with lecanemab may be beneficial in a subset of patients whose disease progressed with more noticeable changes [i.e. change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR SB) score ≥ 1.5]. This post hoc subgroup analysis addressed some of the initial uncertainties related to the clinical meaningfulness of the treatment, providing evidence of benefit in this subgroup of patients who progressed more rapidly. The long-term efficacy of the product remains to be established, and the company will be requested to provide the final results of the open-label extension phase of Study 301, when completed, which should provide longer-term efficacy and safety data. The company also committed to conducting a confirmatory study to confirm the efficacy of Leqembi, and by extension to support the demonstration of a favourable benefit-risk profile. The results for the confirmatory study are expected in 2030.

The indication of Leqembi has been restricted to patients who are carriers of only one allele (heterozygotes) of apolipoprotein E ε4 (ApoE ε4) or noncarriers; these patients showed a more favourable benefit-risk profile compared to patients who carry two alleles of apolipoprotein E ε4 (ApoE ε4 homozygotes). Specifically, heterozygote and noncarrier patients showed less risk of amyloid-related imaging abnormalities (ARIA) associated with brain edema (ARIA-E) and/or bleeding (ARIA-H). ARIAs are the most concerning risks associated with Leqembi treatment, as they can be debilitating and fatal. The incidence of severe ARIA events was also higher in patients who are ApoE ε4 homozygotes, and these patients showed longer recovery times from ARIA with higher rates of recurrent ARIA events. Use of Leqembi in patients who are homozygotes is contraindicated.

Treatment with Leqembi requires a significant amount of monitoring with Magnetic Resonance Imaging (MRI), and Leqembi should be initiated and supervised by a healthcare professional experienced in the diagnosis and treatment of Alzheimer’s disease with timely access to MRI. MRI is an important risk mitigation measure to detect ARIA during treatment and guide clinical decisions that aim to minimize the likelihood of worsening or recurring events.

Safety risks observed with lecanemab treatment have been mitigated in multiple ways, including labelling and by providing instructions to healthcare professionals in the Product Monograph (PM). Additional pharmacovigilance activities and measures were also implemented and include the creation of a Canadian Patient Registry to monitor the safety of Leqembi in the real-world setting over the long term, and the development of educational materials with specific guidance to healthcare professionals, patients and caregivers. Information obtained through the Registry will also be leveraged to help assess the effectiveness of the implemented risk mitigation measures.  

Overall, as labelled, the benefit-risk profile of Leqembi administered as a 10 mg/kg intravenous (IV) once every 2 weeks is considered favourable in adult patients with a clinical diagnosis of mild cognitive impairment or mild dementia due to Alzheimer's disease (early Alzheimer's disease), who are ApoE ε4 noncarriers or heterozygotes, and who have confirmed amyloid pathology.

Therefore, a Notice of Compliance with Conditions (NOC/c) is recommended.

For more information on the conditions issued, please refer to the Notice of Compliance with conditions (NOC/c) Website.

An updated Risk Management Plan (RMP) for Leqembi was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Leqembi has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

For further details about Leqembi, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.