A 400-mg dose of solanezumab every 4 weeks is not associated with a reduction in cognitive decline among patients with mild dementia caused by to Alzheimer disease (AD), according to findings from a phase 3 trial published in the New England Journal of Medicine.
This study included 2129 patients with mild AD as determined by a score of 20 to 26 on the 30-point Mini-Mental State Examination (MMSE) scale and by indications of amyloid deposition imaged by amyloid beta (Aβ) (1-42) measurements or florbetapir positron-emission tomography. Investigators randomly assigned patients to receive 400 mg of intravenous solanezumab (n=1057) or intravenous placebo (n=1072) every 4 weeks for a total of 76 weeks. Change in the baseline score on the 14-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog14) at 80 weeks comprised the primary outcome.
At baseline, the mean (± standard deviation) ADAS-cog14 score was significantly lower in the solanezumab group vs the placebo group (28.9±8.3 vs 29.7±8.5, respectively; P =.02). No significant differences were observed between the intervention and placebo groups in terms of the average baseline MMSE score (22.8±2.8 vs 22.6±2.9, respectively; P =.12).
There were no significant differences between the treatment and placebo groups with regard to change in baseline ADAS-cog14 score at 80 weeks (6.65 vs 7.44, respectively; difference, –0.80; 95% CI, –1.73 to 0.14; P =.10). Similar changes were observed in the solanezumab and placebo groups in baseline MMSE at follow-up (–3.17 vs –3.66, respectively); however, a statistical analysis was not performed to determine a significant difference. A numerically greater number of adverse cerebral edema or effusion lesions occurred in the placebo vs solanezumab group (2 vs 1, respectively).
The 400-mg solanezumab dose used in this study may not have been sufficient to provide clinically meaningful effects in these patients. Additionally, solanezumab is used to clear soluble Aβ from the brain, and if amyloid is not associated with AD, this may possibly explain the results of this study.
Adverse amyloid-related imaging abnormalities were low in the solanezumab group, suggesting that the low incidence of these abnormalities is associated with the hypothesis that, “solanezumab administration may reflect the binding only to soluble Aβ.”
Honig LS, Vellas B, Woodward M, et al. Trial of solanezumab for mild dementia due to Alzheimer’s disease. N Engl J Med. 2018;378(4):321-330.