The New England Journal of MedicineTrial of Solanezumab in Preclinical Alzheimer’s Disease

Could the effectiveness of treatments targeting monomeric amyloid in Alzheimer’s disease patients be related to the stage of the disease at the time of intervention?

In an effort to further understanding of treatment options for preclinical Alzheimer’s disease, a recent phase 3 clinical trial examined the effectiveness of solanezumab, an antibody that targets monomeric amyloid.

Study Design:

• Solanezumab was tested in a phase 3 trial involving individuals with preclinical Alzheimer’s disease.
• The study included persons aged 65 to 85 with no cognitive impairment, scores of 25 or more on the Mini–Mental State Examination, and elevated brain amyloid levels detected through 18F-florbetapir PET.
• 1,169 individuals were enrolled, with 578 in the solanezumab group and 591 in the placebo group.
• Participants were randomized 1:1 to receive either up to 1,600 mg of solanezumab intravenously every 4 weeks or a placebo.
• The primary endpoint was the change in the Preclinical Alzheimer Cognitive Composite (PACC) score over a period of 240 weeks.

Key Findings:

• The mean change in PACC score at 240 weeks was −1.43 in the solanezumab group and −1.13 in the placebo group.
• Brain amyloid levels increased by a mean of 11.6 centiloids in the solanezumab group and 19.3 centiloids in the placebo group.
• Amyloid-related imaging abnormalities with edema occurred in less than 1% of the participants in each group.
• Amyloid-related imaging abnormalities with microhemorrhage or hemosiderosis occurred in 29.2% of the solanezumab group and 32.8% of the placebo group.

Conclusion:

• Solanezumab, which targets monomeric amyloid in persons with elevated brain amyloid levels, was not effective in slowing cognitive decline as compared with placebo over a period of 240 weeks in individuals with preclinical Alzheimer’s disease.

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Did You Know?
Alzheimer’s disease affects around 6.2 million Americans aged 65 and older, as of 2021.