Is lecanemab safe and effective as a treatment of mild cognitive impairment or early Alzheimer's disease?
Similar to aducanumab, lecanemab does an excellent job of reducing amyloid while having very little impact on cognition and function, while causing concerning increases in brain edema and hemorrhage. The advisory committee from the United States Food and Drug Administration (FDA) voted almost unanimously against approval of aducanumab, a vote that was ultimately ignored by the FDA. This time, they didn't even convene an advisory committee and just went ahead and approved lecanemab. These decisions call into question the FDA's decision-making and independence, and also call into question the amyloid hypothesis for Alzheimer's disease.
Plan de l'etude:
Randomized controlled trial (double-blinded)
Lecanemab is a monoclonal antibody that targets amyloid beta in the brain of patients with Alzheimer's disease. This phase 3 trial randomized 1795 participants to receive 10 mg per kg lecanemab or placebo every 2 weeks and followed them up for up to 18 months. At baseline, patients had mild cognitive impairment (69%) or mild Alzheimer's disease (31%); their mean age was 71 years, 52% were women, and their mean Mini–Mental State Examination score was 25 (range 22 - 30; 30 is the best possible score). The primary outcome was the change from baseline on the Clinical Dementia Rating Sum of Box (CDR-SB) score, which measures both cognition and function. The decline in the CDR-SB score at 18 months was slightly less in the lecanemab group (by -0.45 points; 95% CI -0.67 to -0.23). However, this is far less than the minimal clinically important difference (MCID) of 1 to 2 points. Similarly, the Alzheimer's Disease Assessment Scale declined by 1.44 points less in the lecanemab group, which is also less than the MCID of at least 4 points. Serious adverse events occurred more often in the lecanemab group (14.0% vs 11.3%), including symptomatic brain hemorrhages (0.7% vs 0.2%) and symptomatic brain edema (2.8% vs 0.0%). There was no difference between groups in mortality.
Mark H. Ebell, MD, MS
University of Georgia