Alzheimer's disease is a neurodegenerative disorder characterized by progressive cognitive decline and memory impairment, ultimately leading to the loss of ability to perform daily activities. It is the most common cause of dementia, accounting for approximately 60-80% of cases. The disease is primarily associated with the accumulation of abnormal protein structures, such as amyloid plaques and neurofibrillary tangles, in the brain.
Lecanemab is a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils that has recently been approved for treatment of early Alzheimers. Lecanemab is the second of a new category of medications approved for Alzheimer’s disease that target the fundamental pathophysiology of the disease after aducanumab.
In a new article published in The New England Journal of Medicine, lecanemab was tested in a multicenter, double-blind, phase 3 trial involving 1795 participants with either mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease–related dementia.
The primary outcome of interest was the score on the Clinical Dementia Rating (CDR)–Sum of Boxes (CDR-SB) at baseline and at 18 months (about 1 and a half years). Secondary efficacy outcomes included amyloid burden on PET scan.
CDR-SB Score:
The CDR-SB score at baseline in both the treatment and placebo groups were similar at around 3.2, consistent with early Alzheimer’s Disease. At 18 months (about 1 and a half years), the adjusted mean change from baseline was significantly less in the lecanemab group (1.21) compared to the placebo (1.66) (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001)
Amyloid Burden on PET
Among 698 participants, the amyloid burden on PET was not significantly different between the lecanemab and placebo group at baseline. However, the adjusted mean change from baseline at 18 months (about 1 and a half years) was significantly greater in the lecanemab group at −55.48 centiloids compared to the placebo group which had a mean change of 3.64 centiloids (difference, −59.12 centiloids; 95% CI, −62.64 to −55.60; P<0.001)
Conclusion:
Lecanemab was associated with a significant decrease in brain amyloid deposition and moderately diminished decline in the clinical measures of cognition and memory in comparison to placebo in patients with early Alzheimer’s disease. Although lecanemab is not a cure for early Alzheimer’s, current evidence has shown a slowing in disease progression in patients taking the drug. Longer trials, however, remain warranted.
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