Analysis of EXPEDITION trials of solanezumab in mild Alzheimers disease suggests benefits- Eli Lilly

Eli Lilly and Company announced results suggesting the treatment effect of solanezumab was preserved within a pre-specified amount in patients with mild Alzheimer's disease who received solanezumab earlier in the disease compared to patients who began treatment at a later point. These results were from a pre-specified secondary analysis of the Phase III EXPEDITION, EXPEDITION 2 and EXPEDITION-EXT studies, and were presented at the Alzheimer's Association International Conference 2015 (AAIC) in Washington, D.C. These results support the use of the "delayed-start" method for assessing the potential effects of a treatment on the underlying disease progression of Alzheimer's disease. Results from this study are expected to be published online in Alzheimer's & Dementia: Translational Research & Clinical Interventions.

The objective of the delayed-start analysis was to assess a possible disease-modifying effect of solanezumab in patients with mild Alzheimer's disease. These results were obtained from a pre-specified secondary analysis of the Phase III EXPEDITION, EXPEDITION 2 and EXPEDITION-EXT studies. EXPEDITION and EXPEDITION 2 had identical study protocols, which included an 18-month randomized, double-blind, placebo-controlled period, after which a two-year delayed-start period occurred (EXPEDITION-EXT), where the placebo-treated patients from the placebo-controlled period began treatment with solanezumab. Results from EXPEDITION and EXPEDITION 2 were pooled and only patients with mild dementia at the beginning of the study were included in this analysis. During the delayed-start period, the original treatment assignment remained blinded to patients and sites. When considering the placebo-controlled period and delayed-start period together, all patients were randomized to the same active treatment (solanezumab) but starting at different times, resulting in two treatment regimens: early-start and delayed-start. The primary analysis was at 108 weeks after the beginning of the placebo-controlled period (28 weeks after the beginning of the delayed-start period) among the subgroup of patients with mild Alzheimer's disease at baseline. To assess whether the benefits of early treatment can be matched by later treatment (that is, whether delayed-start patients can "catch up" with early-start patients), a noninferiority test was conducted.

Key Results Highlights: Treatment differences in cognition and function between early-start and delayed-start groups at the end of the placebo-controlled period (80 weeks since randomization) were preserved at the primary time point of 108 weeks (28 weeks after the start of EXPEDITION-EXT) within a pre-defined margin. This difference at 108 weeks remained statistically significant. Treatment differences in cognition and function between early-start and delayed-start groups at the end of the placebo-controlled period (80 weeks since randomization) were also preserved at an additional time point of 132 weeks (52 weeks after the start of EXPEDITION-EXT) within a pre-defined margin. This difference at 132 weeks was statistically significant.