More than 80 percent of patients with early Alzheimer’s disease treated with lecanemab remained clinically stable or improved over an average of 17 months.Three years post-initial US FDA approval, lecanemab still shows ongoing clinical benefits and reduces amyloid plaques in patients with early Alzheimer’s disease (AD).
In an interim analysis of the real-world LEADER study presented at AAIC 2026, more than 80 percent of patients with early Alzheimer’s disease (AD) treated with lecanemab in routine practice remained clinically stable or improved over an average of 17 months.
Among 427 evaluable patients followed for an average of 17 months, 75.9 percent remained stable, 6.6 percent improved from mild AD to mild cognitive impairment (MCI), and 17.6 percent showed disease progression on clinical assessment.
Lead investigator Dr Babak Tousi, director of the Cleveland Clinic Center for Brain Health in Cleveland, Ohio, US, said the results were consistent across sex, race, ethnicity, and apolipoprotein E epsilon 4 (ApoE-ε4) genotype. “These findings suggest that the benefits observed in the phase III CLARITY-AD trial, which earned lecanemab its approval 3 years ago, are being translated into routine clinical practice across diverse treatment settings,” he added.
Real-world study, long-term data
LEADER is one of the largest real-world assessments of lecanemab since its approval in 2023. The study included patients treated by dementia specialists and general neurologists in academic and community settings across the US.
The interim analysis included 432 patients with early AD who had received at least seven lecanemab infusions by May 2026. Their mean age was 74 years, 55.8 percent were women, 63.9 percent had mild cognitive impairment (MCI) due to AD, and 36.1 percent had mild AD at the start of treatment. The mean treatment duration was 520 days, roughly 26 doses. [AAIC 2026, abstract 13216]
Tousi estimated that after 30 months of treatment, 87.8 percent of patients would still be in the early stages of AD.
Analyses by ApoE-ε4 status showed that a clinician-evaluated stable or improved disease stage was observed in 81.7 percent of ApoE-ε4 heterozygotes (stable, 73.8 percent; improved, 7.9 percent) and in 81 percent of ApoE-ε4 homozygotes (stable, 75.9 percent; improved, 5.2 percent).
At the time of assessment, 86.6 percent of patients remained on lecanemab, whereas 13.4 percent discontinued therapy. Reasons for discontinuation included amyloid-related imaging abnormalities (ARIA), infusion reactions, lack of efficacy, patient preference, logistical issues, and other adverse events.
Among 155 patients who switched to once-monthly intravenous maintenance therapy, 72.3 percent remained stable and 8.4 per cent showed improvement. Fourteen patients switched to once-weekly subcutaneous maintenance therapy, and 12 of them maintained their disease stage.
Additionally, cognitive measures collected in subsets of patients showed relatively modest changes over follow-up, with mean declines of 1.0 point on the Montreal Cognitive Assessment and 1.6 points on the Mini-Mental State Examination. Functional Assessment Questionnaire scores increased by 2.0 points.
Safety consistent with previous trials
Overall, ARIA occurred in 12.3 percent of patients, with 6.3 percent experiencing ARIA-E and 7.9 percent experiencing ARIA-H. Most events were mild and asymptomatic. Among patients on monthly maintenance doses, there were no new cases of ARIA-E, macrohaemorrhages, or intracerebral haemorrhages larger than 1 cm.
“Antithrombotic use was not associated with a meaningful increase in ARIA risk in this cohort,” said Tousi. Nonetheless, he emphasised that “careful patient selection and MRI monitoring remain essential for our patients.”