Moving Forward: Alzheimer Treatment Granted Breakthrough Therapy Designation


More potential good news for treating Alzheimer disease, as an 18-month open-label extension for lecanemab allows for its breakthrough status.



Eisai and Biogen’s lecanemab was granted breakthrough therapy designation by the US Food and Drug Administration (FDA) following the 18-month open-label extension (OLE) of the phase 2b proof-of-concept study in patients with early Alzheimer disease (AD). The announcement was shared by the companies at the Alzheimer’s Association International Conference (AAIC) held in Denver, Colorado, virtually held on July 26-30, 2021.

“The findings from the lecanemab Phase 2b OLE study are encouraging as they supply further insights into outcomes with anti-amyloid therapies and we look forward to learning more in the phase 3 studies, Clarity AD and AHEAD 3-45, currently underway,” said Lynn Kramer, MD, Chief Clinical Officer of the Neurology Business Group at Eisai. “The unprecedented confluence of medical knowledge, data analytics, and technological advances make it an incredibly exciting time for Alzheimer research.”1

Lecanemab is an investigational monoclonal antibody that preferentially binds to soluble amyloid-beta (Aβ) aggregates. The treatment reduced brain Aβ and slowed clinical decline in the 18-month phase 2b proof of concept study examining early AD.2

Post core study, researchers implemented an off-treatment gap period of 9 to 59 months, with an average of 24 months. Following this off-treatment gap, researchers evaluated 10mg/kg IC biweekly lecanemab dosing, assessing the clinical effect via the adjusted mean change of the AD Composite Score (ADCOMS), which was the primary clinical endpoint of the core study. The ADCOMS scale ranges from a score of 0.00 to 1.97, with higher score indicating greater impairment.

Participants who received 10 mg/kg IV performed better than those who received placebo on ADCOMS. Additionally, while off-treatment, participants declined at the same rate on key clinical measures in all core treatment groups. The increase in adjusted mean change between the 3 month core study follow up and OLE baseline for lecanemab biweekly, lecanemab monthly, and placebo dosing respectively were 0.11 (0.07 to 0.18 ), 0.10 (0.12 to 0.22) and 0.09 (0.19 to 0.28) for ADCOMS. This suggests lecanemab has a potential disease-modifying effect.

Low values of plasma Aβ42/40 are recognized as an indicator of elevated amyloid in the brain, and were assessed in a subset of participants in the study. The plasma Aβ42/40 ratio increased during the core phase and OLE in participants treated with lecanemab and decreased during the gap period, suggesting a potential relationship between the plasma Aβ42/40 ratio and treatment.

“The findings from the Open-Label Extension further strengthen our belief in the potential of addressing amyloid beta pathology in Alzheimer disease. We look forward to our ongoing collaboration with Eisai to study lecanemab and continuing to pioneer to address the high unmet need for Alzheimer disease patients,” said Alfred Sandrock, Jr, MD, PhD, Head of Research and Development at Biogen.

These findings, as they are based on limited data, are being further evaluated in the ongoing phase 3 Clarity study for early AD. In March 2021, 1795 participants with early AD were enrolled, and the study is expected to be completed by the end of September 2022. The phase 3 clinical study, AHEAD 3-45, is currently evaluating lecanemab in individuals with preclinical AD.


1. Late-breaking AAIC presentation explores potential clinical effects of lecanemab (BAN2401). PR Newswire. News release. July 29, 2021.

2. Swanson CJ, Zhang Y, Dhadda S, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimers Res Ther. 2021;13(1):80. 

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