Veburecestat in Alzheimer's disease (12 mg)
Trial question
What is the effect of verubecestat in patients with mild-to-moderate Alzheimer's disease?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
54.0% female
46.0% male
N = 1305
1305 patients (704 female, 601 male)
Inclusion criteria: patients with a clinical diagnosis of mild-to-moderate Alzheimer's disease
Key exclusion criteria: history of stroke; neurological disorder other than Alzheimer's disease; seizures or epilepsy within the last 5 years; alcohol use disorder or drug dependency/abuse within the last 5 years; hepatitis or liver disease that has been active within the 6 months prior to screening visit; long QT syndrome
Interventions
N=652 verubecestat (12 mg/day)
N=653 placebo (matching placebo)
Primary outcome
Change in ADAS-cog score at 78 weeks
7.9
7.7
7.9 points
5.9 points
4.0 points
2.0 points
0.0 points
Verubecestat
Placebo
No significant
difference ↔
No significant difference in change in ADAS-cog score at 78 weeks (7.9 points vs. 7.7 points; MD 0.2, 97.5% CI -0.9 to 0.13)
Secondary outcomes
No significant difference in change in ADCS-ADL score at 78 weeks (-8.4 points vs. -8.9 points; MD 0.32, 97.5% CI -1.1 to 2.1)
Safety outcomes
No significant differences in adverse events, including syncope, and basal cell carcinoma.
Conclusion
In patients with a clinical diagnosis of mild-to-moderate Alzheimer's disease, verubecestat was not superior to placebo with respect to change in ADAS-cog score at 78 weeks.
Reference
Egan MF, Kost J, Tariot PN et al. Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease. N Engl J Med. 2018 May 3;378(18):1691-1703.
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