Solanezumab: Additional Phase III data

Eli Lilly reported additional data from the 18-month, double-blind, international Phase III EXPEDITION1 and EXPEDITION2 trials in over 2,050 patients with AD who received 400 mg IV solanezumab every 4 weeks. Pooled data from both trials showed that in patients with mild AD, solanezumab led to a significant 34% reduction in cognitive decline as measured by ADAS-Cog14 scores from baseline to week 80 vs. placebo (p=0.001). Pooled data also showed that patients with mild AD had a non-significant 17% reduction in functional decline as measured by ADCS-ADL scores vs. placebo (p=0.057). Additionally, solanezumab significantly improved MMSE scores from baseline to week 80 in both the pooled overall (p=0.002) and mild AD populations (p=0.001) vs. placebo. Mild AD was defined as a baseline MMSE score of 20-26 points and moderate AD was defined as a baseline MMSE score of 16-19 points. Data were presented at the American Neurological Association meeting in Boston.

Eli Lilly previously reported that solanezumab missed the primary endpoints vs. placebo in both trials. Specifically, data from EXPEDITION1 showed that solanezumab missed the co-primary endpoints of improving cognitive (ADAS-Cog11) and functional (ADCS-ADL) scores from baseline to week 80 vs. placebo (p=0.312 and p=0.931). A pre-specified secondary subgroup analysis showed that solanezumab did significantly improve ADAS-Cog11 scores vs. placebo in patients with mild AD (p=0.008). Based on the data, Eli Lilly modified the statistical analysis plan for EXPEDITION2 prior to database lock to specify a single primary endpoint of ADAS-Cog14 scores from baseline to week 80 in patients with mild AD. However, solanezumab missed the single primary endpoint vs. placebo in EXPEDITION2 (20% reduction in cognitive decline vs. placebo, p=0.12). In EXPEDITION2, solanezumab led to a non-significant 19% reduction in functional decline as measured by ADCS-ADL scores in patients with mild AD vs. placebo (p=0.76). ...