Biogen Showcases Promising 4-Year Data for Alzheimer Therapy Lecanemab at AAIC 2025

Christopher van Dyck, MD

Newly presented data from the open-label extension (OLE) of the phase 3 Clarity AD trial (NCT03887455) provided greater context on the efficacy and safety of lecanemab (Leqembi; Eisai), an FDA-approved treatment for early-stage Alzheimer disease (AD), over a 4-year period.¹

Presented at the 2025 Alzheimer’s Association International Conference (AAIC), held July 27-31, in Toronto, Canada, early-stage patients–who were identified through MK6240 tracer–gained the most from lecanemab treatment. According to a release from Biogen, after 4 years of treatment, 69% of patients identified through this optional tau substudy either improved or had no decline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) cognitive and functional domains, a quantitative scale of dementia severity.

The newly presented data expand on the 3-year findings presented at last year’s AAIC meeting by lead investigator Christopher van Dyck, MD, director of the Yale Alzheimer’s Disease Research Center. Overall, 95% of the original 1795 patients (lecanemab: n = 898; placebo: n = 897) who completed the 18-month core study moved onto the OLE, with 478 who had been on treatment for 4 years total.

The optional tau substudy, or the low tau population, included only 36 patients who had at least a 48-month visit. Within this patient group, 56% had improved from baseline in CDR-SB. On the ADAS-Cog14 scale, 51% of patients showed improvement or no decline (with 51% improving), while on the ADCS MCI-ADL scale, 64% showed improvement or no decline and 58% improved.

READ MORE: Glutaminyl Inhibitor Varoglutamstat Fails to Show Efficacy in Phase 2 VIVA-MIND Study of Early Alzheimer Disease

When compared with the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort, those on the anti-amyloid treatment had a mean CDR-SB reduction of –1.01 points over a 3-year period, which rose even larger at the 4-year time point (–1.75 points). ARIA rates, a safety concern for anti-amyloid treatments like lecanemab, were reportedly lower after the initial 12 months and remained consistent throughout the 4-year period. For context, ARIA-edema and ARIA cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis (ARIA-H) occurred in 12.5% and 17.3% of treated patients, respectively, in the original Clarity AD study.²

In the latest data presented at AAIC 2025, lecanemab-treated patients demonstrated a 1.40-point difference in CDR-SB at 3 years when benchmarked against the expected decline in the BioFINDER cohort, a longitudinal research study focused on biomarkers for early diagnosis and tracking of AD. This reduction grew at the 4-year time point, with a difference of 2.17 points.

Lecanemab, a humanized monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid-ß, became the second approved treatment of its class in 2023.³ Since then, the FDA has approved an intravenous maintenance dosing option for the therapy and is currently reviewing an application for an autoinjector formulation as well. The decision, expected to come on August 31, would decide whether lecanemab is the first AD treatment for at-home subcutaneous administration using an autoinejector.⁴

The anticipated autoinjector is expected to take about 15 seconds to administer, still intended for patients with mild cognitive impairment or mild dementia stage of the disease, the population in which treatment was initiated in clinical trials. Several in the field hope this new subcutaneous autoinjector will ease patient care, as well as reduce the need for hospital or infusion site visits and nursing care for intravenous administration.

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REFERENCES
1. Early Alzheimer’s Patients Continue to Benefit from Four Years of LEQEMBI® (lecanemab-irmb) Therapy New Clinical Data Presented at AAIC. News release. Biogen. July 30, 2025. Accessed July 30, 2025. https://investors.biogen.com/news-releases/news-release-details/early-alzheimers-patients-continue-benefit-four-years-leqembir
2. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388:9-21. doi:10.1056/NEJMoa2212948
3. FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval. FDA. News release. July 6, 2023. Accessed July 30, 2025. https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval
4. FDA Accepts LEQEMBI® (lecanemab-irmb) Biologics License Application for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer's Disease. News release. Eisai. January 13, 2025. Accessed July 30, 2025. https://www.prnewswire.com/news-releases/fda-accepts-leqembi-lecanemab-irmb-biologics-license-application-for-subcutaneous-maintenance-dosing-for-the-treatment-of-early-alzheimers-disease-302349842.html