The supplemental BLA is based on data from a confirmatory phase 3 trial. The submission was made the same day Eisai/Biogen received accelerated approval.
Just after receiving accelerated approval for Leqembi (lecanemab-irmb) to treat patients with early Alzheimer’s disease, Eisai/Biogen have submitted a supplemental biologics license application (sBLA) for full approval. Leqembi is humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta.
The supplemental application is based on the data from the phase 3 confirmatory Clarity AD clinical trial. In Clarity AD, Leqembi met the primary endpoint and all key secondary endpoints with highly statistically significant results, and the profile of Amyloid-Related Imaging Abnormalities (ARIA) incidence was within expectations. In November 2022, the results of the Clarity AD study were presented at the 2022 Clinical Trials on Alzheimer's Disease (CTAD) conference, and also published in the Jan. 5, 2023, issue of The New England Journal of Medicine.
Clarity AD was an 18-month phase 3 trial that enrolled 1,795 people aged 50 to 90. The modified intention-to- treat population included 1,734 participants with 859 in the lecanemab group and 875 in the placebo group. The primary endpoint was Clinical Dementia Rating–Sum of Boxes, a commonly used measure to score the stage of patients with Alzheimer’s disease.
In this study, lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months.
But lecanemab resulted in infusion-related reactions in 26.4% of the patients and amyloid-related imaging abnormalities with edema or effusions in 12.6% of patients. Serious adverse events occurred in 14.0% of the participants in the lecanemab group and 11.3% of those in the placebo group. The most commonly reported serious adverse events were infusion-related re- actions. Adverse events leading to discontinuation of the trial agent occurred in 6.9% of the participants in the lecanemab group and 2.9% of those in the placebo group.