The experimental Alzheimer's treatment lecanemab, developed by Eisai and Biogen, has demonstrated significant efficacy in slowing cognitive decline while raising important safety considerations, according to new clinical trial data presented in San Francisco.
The 18-month study, involving nearly 1,800 participants with early-stage Alzheimer's disease, showed that lecanemab reduced cognitive decline by 27% compared to placebo as measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB).
Safety Profile and Risk Considerations
The trial data revealed notable safety signals that warrant careful consideration. Among participants, 12.6% experienced amyloid-related imaging abnormalities (ARIA) manifesting as brain swelling, while 14% developed brain microhemorrhages. Five patients suffered more serious macrohemorrhages during the study period.
Dr. Ronald Petersen of the Mayo Clinic in Rochester, Minnesota, contextualized these findings: "All of these amyloid-lowering drugs carry a risk for increased brain hemorrhage. I think the primary outcomes, the secondary outcomes, the amyloid-lowering is pretty impressive."
Genetic Factors and Treatment Response
The drug's efficacy showed variation across genetic subgroups. Notably, patients carrying two copies of the APOE4 gene variant - representing approximately 16% of participants - did not demonstrate improvement on the primary CDR-SB measure. However, these patients did show positive responses on secondary endpoints, with overall benefits ranging from 23% to 37% across various cognitive and functional measures.
Amyloid Clearance and Mechanism of Action
The trial provides substantial support for the amyloid hypothesis in Alzheimer's treatment. Eisai reported that 68% of treated participants showed amyloid clearance at 18 months, supporting the theory that removing amyloid beta deposits from the brain can slow disease progression.
Future Implications and Regulatory Status
Dr. Paul Aisen, director of the USC Alzheimer's Therapeutic Research Institute and study co-author, expressed optimism about the drug's potential: "I believe it's an important benefit that will justify full approval. But of course, we want a bigger benefit." He suggested that earlier intervention might yield superior results, "before you've accumulated enough irreversible damage to be causing symptoms."
The FDA is expected to decide on lecanemab's accelerated approval by January 6, based on its ability to impact amyloid beta levels in the brain. Eisai has confirmed plans to pursue standard FDA approval and seek regulatory clearance in Europe and Japan.
Safety Monitoring and Patient Selection
While two deaths occurred in the trial extension phase, Eisai maintains these cannot be attributed to lecanemab. However, Dr. Howard Fillit, chief science officer at the Alzheimer's Drug Discovery Foundation, advised caution for certain patient groups: "Currently, I would hesitate to give this drug to someone on blood thinners."
The Alzheimer's Association has endorsed the findings, stating the data confirms lecanemab "can meaningfully change the course of the disease for people in the earliest stages of Alzheimer's disease," and has advocated for regulatory approval.
