The expanding long-term benefit with lecanemab is consistent with a disease-modifying effect in Alzheimer's disease.The 48-month analysis of the global phase III Clarity AD study shows that lecanemab continues to deliver benefit and delay progression in early Alzheimer's disease (AD).
“An increasing treatment difference is observed with ongoing lecanemab treatment in participants treated through 48 months compared with the matched controls, ie, the ADNI* and Swedish BioFINDER cohorts,” said Dr Steven Hersch from Eisai Inc, Nutley, New Jersey, US, at AAN 2026.
Lecanemab-treated patients continued to accrue benefit over time and lecanemab extended time spent in early disease, with an increasing magnitude of treatment effect over time, he added.
Between the lecanemab and ADNI groups, the adjusted mean changes in CDR-SB** at 18, 36, and 48 months were 0.52, 1.01, and 1.75, respectively. Between the lecanemab and BioFINDER cohorts, the corresponding differences were 0.57, 1.40, and 2.17.
Lecanemab meaningfully delayed progression to dementia stage (moderate or severe) through 48 months (time saved 10.7–13.1 months). Eighty-one percent of patients who stayed on lecanemab remained in the early AD stages. [AAN 2026, abstract S1.005]
Compared with the ADNI cohort, the lecanemab group had a reduction in the relative risk of progression to dementia disease stage by 56 percent (time to worsening on CDR-SB, hazard ratio, 0.44; p<0.00001).
The proportion of patients who progressed to dementia stage was halved in the lecanemab group vs the ADNI group (18.6 percent vs 37.4 percent).
Moreover, early-stage participants continued to benefit from lecanemab through 48 months. There were consistent rates of clinical stability or improvements across assessments regardless of baseline tau levels, with the highest rates of improvements observed for the no/low tau group at 48 months (‘No Decline’: 69, 51, and 64 percent for CDR-SB, ADAS-Cog14**, and ADCS MCI-ADL**, respectively; ‘Improvement’: 56, 51, and 58 percent, respectively).
There were no new safety signals. The rates of ARIA with edema or effusion (ARIA-E; 12.6 percent and 15 percent in the double-blind [DB] and DB + open-label extension [OLE] phases) and ARIA with haemorrhage/hemosiderin (ARIA-H; 16.9 percent and 25.8 percent, respectively) are consistent with what is expected of the drug.
The rates of serious adverse events (AEs), AEs leading to study drug withdrawal, and isolated ARIA-H with lecanemab in the DB phase were 14, 7.1, and 8.7 percent, respectively. In the combined DB + OLE phases, the corresponding rates were 22.8, 11.1, and 14.5 percent.
“The rates of AEs and ARIA by 12-month intervals continued to show a decreasing pattern … Essentially, the risks of particular concern are frontloaded and diminished after 3–6 months,” said Hersch.
“ARIA-E events are very rare after the first 6 months—the risk was greatest in the first 3 months and generally occurs before 6 months. The risk period for ARIA-E is the first 6 months based on vascular amyloid clearance and increased permeability,” he said.
Disease-modifying effect
Clarity AD comprised 1,795 individuals with mild cognitive impairment due to AD or mild Alzheimer’s dementia and confirmed amyloid pathology. They were randomized 1:1 to IV lecanemab 10 mg/kg biweekly or placebo for 18 months. An OLE phase ensued, during which all participants received lecanemab (IV 10 mg/kg biweekly or monthly, or subcutaneous) for 4 years.
“[Taken together, the] pronounced benefit in the earliest participants supports early diagnosis and treatment. The expanding long-term benefit [with lecanemab] is consistent with a disease-modifying effect,” said Hersch.