Long‐term safety and efficacy of lecanemab in early Alzheimer's disease: Results from the clarity AD open‐label extension study

Abstract INTRODUCTION In Clarity AD, lecanemab reduced markers of amyloid in early symptomatic Alzheimer's disease and slowed cognitive and functional decline at 18 months. Herein, we report 36‐month data from the ongoing open‐label extension (OLE). METHODS Clarity AD is an 18‐month, randomized study (Core), with an OLE where participants received open‐label lecanemab. Clinical and health‐related quality‐of‐life (HRQoL) outcomes were evaluated overall and by examining “delayed‐start” and “early‐start” cohorts. Low pathology (i.e., low baseline amyloid or tau) subgroups were analyzed. RESULTS ARIA rates were low after 6 months and not associated with long‐term progression. Across clinical and HRQoL endpoints, lecanemab‐treated participants continued to benefit through 36 months. Separation between early and delayed start was maintained between 18 and 36 months. The low pathology subgroup showed stability or improvement over 18–36 months. DISCUSSION Benefit continued to accrue with ongoing lecanemab treatment through 36 months. Results in the low pathology subgroup support early initiation of lecanemab treatment. Highlights This research evaluated the long‐term efficacy, safety, and HRQoL results from an ongoing extension of the phase 3 Clarity AD, which included open‐label lecanemab treatment for up to 36 months. Overall, the results show participants continue to accrue a lecanemab treatment benefit up to 36 months and highlight the importance of continued long‐term lecanemab treatment. Results presented in our paper demonstrate that lecanemab continued suppression of amyloid plaque levels and significantly slowed clinical decline on multiple measures of cognition, function, and quality of life in early AD at 18 months and continued for 36 months to date. No new safety signals were observed with continued lecanemab treatment. After the first 6 months, ARIA rates were low and similar to ARIA rates on placebo, with no association between ARIA occurrence and accelerated long‐term clinical progression. Taken together with existing data, these results provide a clear rationale and a demonstration of the disease modification effects of long‐term lecanemab therapy.