On 30 November, Eisai and Biogen announced that the results from the Phase III Clarity AD trial of lecanemab (also known as BAN2401), an investigational anti-amyloid beta protofibril antibody, for the treatment of early Alzheimer’s disease (AD) were presented at the 2022 Clinical Trials on Alzheimer's Disease (CTAD) conference in San Francisco (US). Findings were published simultaneously in the New England Journal of Medicine.
Clarity AD was a global confirmatory Phase III placebo-controlled, double-blind, parallel-group and randomised study evaluating lecanemab in 1,795 people with mild cognitive impairment due to AD or mild AD dementia (collectively known as early AD) with confirmed amyloid accumulation in the brain. Participants from US, Australia, Canada, China, Europe and Japan received either lecanemab (10 mg/kg) or placebo biweekly via an intravenous infusion. An estimated 25% of the total enrolment in the US included Hispanic and African American people with early AD.
The study met its primary endpoint, showing a statistically significant reduction of cognitive decline on the global cognitive and functional scale, CDR-SB, by 27% at 18 months for participants receiving lecanemab compared to those receiving placebo.
Secondary endpoints were also met with statistically significant results compared with placebo at 18 months including reduction in amyloid plaque burden. Lecanemab slowed decline of cognitive function by 26% on ADAS-Cog14 and slowed disease progression by 24% on ADCOMS at 18 months. Additionally, lecanemab slowed decline of activities of daily living by 37% on ADCS MCI-ADL at 18 months.
The most common adverse events in the lecanemab group were infusion reactions, amyloid-related imaging abnormalities (ARIA), headache and fall. The incidence of ARIA-E (edema/effusion) was within expectations. ARIA-E occurred in 12.6% of the lecanemab group and 1.7% in the placebo group. Symptomatic ARIA-E occurred at a rate of 2.8% in the lecanemab group and 0% in the placebo group. ARIA-E events most commonly occurred within the first three months of treatment (71% of those who had ARIA-E) and resolved within four months of detection (81% of those who had ARIA-E). The rate of ARIA-H (cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis) was 17.3% for lecanemab compared with 9% for placebo, while symptomatic ARIA-H occurred at a rate of 1.4% in the lecanemab group and 0.2% in the placebo group.
Eisai will discuss the results of the Clarity AD study with regulatory authorities with the aim to file for traditional approval in the US and to submit marketing authorisation applications in Japan and Europe by the end of March 2023.