At December’s Clinical Trials in Alzheimer’s Disease conference, Eisai reported that its clinical trial of E2027 in dementia with Lewy bodies (DLB) failed to meet its primary objective. Designed as a “Phase 2/3” trial, the purpose was to assess whether the study drug is safe, what side effects it might have, and if it produces the desired treatment response.
The 12-week trial of irsenontrine included 196 people with dementia with Lewy bodies. Participants were randomized into two groups receiving the study drug or a placebo. The goal was to measure the drug’s ability to improve cognitive function compared to placebo.
The primary outcome measures used included the Montreal Cognitive Assessment (eMoCA) and the electronic Clinician’s Interview Based Impression of Change plus Caregiver Input (eCIBIC-plus).
The mean baseline eMoCA score for the cohort was approximately 14 out of 30. It is possible that studying a group of DLB individuals at the latter part of the moderate stage may have reduced the possibility of seeing treatment effect. Alternatively, the eMoCA may not be able to sufficiently capture cognitive change in DLB as a primary outcome in a clinical trial. The eCIBIC-plus has been used extensively in Alzheimer’s disease clinical trials but may not be the most appropriate global outcome for DLB clinical trials.
After the study was over, exploratory analysis was done to compare the differences in response between two sub-groups – participants who had pure DLB compared to those who had DLB plus Alzheimer’s disease (DLB-AD) changes in the brain. While the results did not reach statistical significance, the group with pure DLB who received CT-1812 did tend to show greater improvement in the e-MoCA and the 3CIBIC-plus.
This later exploratory analysis provides meaningful insight that reinforces the importance of detecting co-existing diseases in clinical trial design in both DLB and Alzheimer’s disease. Future clinical trial designs may need to consider pre-planned analyses of pure DLB vs. mixed DLB-AD.