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Semagacestat Fails Alzheimer’s Trial
Drug doesn’t improve cognitive status (July 25)
According to a new study in the New England Journal of Medicine, treatment with semagacestat (Eli Lilly), an investigational small-molecule gamma-secretase inhibitor, does not improve cognitive status and is associated with worsening of cognitive function in patients with Alzheimer's disease (AD).
In the phase III, double-blind, placebo-controlled trial, a total of 1,537 AD patients were randomly assigned to receive semagacestat (100 mg or 140 mg) or placebo once daily. Cognitive changes from baseline to week 76 were assessed using the cognitive subscale of the Alzheimer’s Disease Assessment Scale for cognition (ADAS-cog), and changes in functioning were evaluated with the Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale.
The study was terminated early on the recommendation of a data and safety monitoring board. At termination, 189 patients were in the placebo group; 153 patients were in the semagacestat 100-mg group; and 121 patients were in the semagacestat 140-mg group.
ADAS-cog scores worsened in all three treatment groups (mean change: 6.4 points in the placebo group, 7.5 points in the group receiving 100 mg of the study drug, and 7.8 points in the group receiving 140 mg; P = 0.15 and P = 0.07, respectively, for the comparison with placebo).
ADCS-ADL scores also worsened in all three groups (mean change at week 76: –9.0 points in the placebo group, –10.5 points in the 100-mg group, and –12.6 points in the 140-mg group; P = 0.14 and P < 0.001, respectively, for the comparison with placebo).
Compared with the placebo group, patients treated with semagacestat lost more weight, had more skin cancers and infections, had more treatment discontinuations due to adverse events, and experienced more serious adverse events (P < 0.001 for all comparisons).
Source: NEJM; July 25, 2013.