FDA clears LEQEMBI injection for Treatment of Alzheimer's Disease

The U.S. Food and Drug Administration's (FDA) Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) has voted unanimously that the data from Eisai's Phase 3 Clarity AD clinical trial confirms the clinical benefit of LEQEMBI (lecanemab-irmb) 100 mg/mL injection for intravenous use for the treatment of Alzheimer's disease (AD). Additionally, the committee members confirmed the overall benefit-risk profile of LEQEMBI, the clinical meaningfulness of the data and discussed its use in specific subgroups, including Apolipoprotein E (ApoE) ε4 homozygote patients, patients requiring concomitant treatment with anticoagulant agents, and patients with cerebral amyloid angiopathy.

LEQEMBI has been approved under the FDA accelerated approval pathway. 

The unanimous decision by the panel of independent experts was based on the supplementary Biologics License Application (sBLA) which includes data from Eisai's large global confirmatory Phase 3 Clarity AD trial. The Clarity AD trial met its prespecified primary endpoint, demonstrating a highly statistically significant slowing of cognitive and functional decline (27%, p=0.00005) compared to placebo over 18 months. Highly statistically significant treatment effects were also observed for all multiplicity-controlled secondary endpoints that examined cognition and functional changes using other validated scales.

The most common adverse events (>10%) in the LEQEMBI group were infusion reactions (LEQEMBI: 26.4%; placebo: 7.4%), ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis: LEQEMBI: 17.3%; placebo: 9.0%), ARIA-E (edema/effusion: LEQEMBI: 12.6%; placebo: 1.7%), headache (LEQEMBI: 11.1%; placebo: 8.1%), and fall (LEQEMBl: 10.4%; placebo: 9.6%). Infusion reactions were largely mild-to-moderate (grade 1-2: 96%) and occurred on the first dose (75%). The results of the Clarity AD study were presented at the Clinical Trials on Alzheimer's Disease (CTAD) conference and simultaneously published in the peer- reviewed medical journal, The New England Journal of Medicine.

LEQEMBI, a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril*) and insoluble forms of amyloid beta (Aβ), received accelerated approval on January 6, 2023, and was launched in the U.S. on January 18, 2023. The accelerated approval was based on Phase 2 data that demonstrated that LEQEMBI reduced the accumulation of Aβ plaque in the brain, a defining feature of AD. Its continued approval may be contingent upon verification of LEQEMBI's clinical benefit in the confirmatory Clarity AD trial (Study 301). The advisory committee agreed unanimously that Study 301 verified the clinical benefit. The Prescription Drug User Fee Act (PDUFA) action date for the traditional approval is July 6, 2023.

Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.