Lecanemab, an experimental drug developed by Biogen and Eisai, has demonstrated potential in slowing the progression of Alzheimer's disease, according to Phase 3 trial results published in the New England Journal of Medicine. The study revealed a 27% reduction in cognitive and functional decline in patients with early Alzheimer's who received lecanemab compared to those who received a placebo.
The Phase 3 trial, conducted across 235 sites in North America, Europe, and Asia, involved 1,795 adults aged 50 to 90 with mild cognitive impairment or mild Alzheimer's dementia. Participants were randomized to receive either lecanemab intravenously every two weeks or a placebo.
Amyloid Reduction and Cognitive Benefits
The study's primary endpoint was the change in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. At baseline, both groups had an average CDR-SB score of approximately 3.2. After 18 months, the lecanemab group's score increased by 1.21 points, while the placebo group's score increased by 1.66 points, indicating a statistically significant difference (p<0.05).
"Significant differences emerge as early as the six-month timepoint," said Dr. Christopher van Dyck, an author of the study and director of the Yale Alzheimer's Disease Research Center, during a presentation at the Clinical Trials On Alzheimer's Disease Conference.
Lecanemab, a monoclonal antibody, targets amyloid beta, a hallmark of Alzheimer's disease. The trial demonstrated that lecanemab effectively reduced amyloid levels in the brain. At 18 months, the average amyloid level decreased by 55.48 centiloids in the lecanemab group, while it increased by 3.64 centiloids in the placebo group.
Safety Considerations and Adverse Events
While lecanemab showed promising results, the trial also highlighted safety concerns. Approximately 6.9% of participants in the lecanemab group discontinued the trial due to adverse events, compared to 2.9% in the placebo group. Serious adverse events occurred in 14% of the lecanemab group and 11.3% of the placebo group.
The most common adverse events were infusion-related reactions and amyloid-related imaging abnormalities (ARIA), including brain swelling (ARIA-E) and brain bleeding (ARIA-H). ARIA brain bleeding was observed in 17.3% of those receiving lecanemab and 9% of those in the placebo group, while ARIA brain swelling was documented in 12.6% with lecanemab and 1.7% with placebo.
"Lecanemab was generally well-tolerated. Most adverse events were infusion-related reactions, ARIA-H and ARIA-E and headache," said Dr. Marwan Sabbagh, an author of the study and professor at the Barrow Neurological Institute. He added that these events typically resolved within months.
The frequency of ARIA appeared to be higher in individuals carrying the APOE4 gene, a known risk factor for Alzheimer's disease. The researchers noted that ARIA "were numerically less common" among APOE4 noncarriers.
Regulatory Pathway and Future Implications
Eisai aims to file for approval of lecanemab in the United States by the end of March. The FDA has granted lecanemab "priority review" and is expected to decide on accelerated approval by January 6, 2023.
"If and when this drug is approved by the FDA, it will take clinicians some time to be able to parse out how this drug may or may not be effective in their own individual patients," said Dr. Richard Isaacson, adjunct associate professor of neurology at Weill Cornell Medicine.
While lecanemab is not a cure for Alzheimer's, it represents a potential advancement in managing the disease's progression. Further research is needed to fully understand its long-term efficacy and safety profile and to explore its use in combination with other therapies.
