Egan MF, et al. - Verubecestat at doses of 12 mg and 40 mg per day, as compared with placebo, was comparatively analyzed in this randomized, double-blind, placebo-controlled, 78-week trial in patients who had a clinical diagnosis of mild-to-moderate Alzheimer’s disease. No reduction was achieved in cognitive or functional decline in patients with mild-to-moderate Alzheimer’s disease with verubecestat use. Verubecestat therapy had treatment-related adverse events.

Methods

• The coprimary outcomes included change from baseline to week 78 in the score on the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog; scores range from 0 to 70, with higher scores indicating worse dementia) and in the score on the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL; scores range from 0 to 78, with lower scores indicating worse function).

Results

• A total of 1,958 patients were randomized to either receive verubecestat at a dose of 12 mg per day (the 12-mg group, n=653), verubecestat at a dose of 40 mg per day (the 40-mg group, n=652), or matching placebo (n=653).
• It was determined that the estimated mean change from baseline to week 78 in the ADAS-cog score was 7.9 in the 12-mg group, 8.0 in the 40-mg group, and 7.7 in the placebo group (P=0.63 for the comparison between the 12-mg group and the placebo group and P=0.46 for the comparison between the 40-mg group and the placebo group).
• Findings revealed that the estimated mean change from baseline to week 78 in the ADCS-ADL score was -8.4 in the 12-mg group, -8.2 in the 40-mg group, and -8.9 in the placebo group (P=0.49 for the comparison between the 12-mg group and the placebo group and P=0.32 for the comparison between the 40-mg group and the placebo group).
• In the verubecestat groups, adverse events, including rash, falls and injuries, sleep disturbance, suicidal ideation, weight loss, and hair-color change, were more common than in the placebo group.
• The trial was ended early for futility 50 months after commencement, which was within 5 months before its scheduled completion.