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EEG FINDINGS IN A PHASE 2 STUDY OF THE ORAL P38Α KINASE INHIBITOR NEFLAMAPIMOD IN PATIENTS WITH MILD-TO-MODERATE DEMENTIA WITH LEWY BODIES (DLB)
Abstract
Aims
Neflamapimod targets pathogenic mechanisms considered to underlie basal forebrain cholinergic (BFC) neurodegeneration, a major driver of dementia in DLB. In a recent phase 2 study in mild-to-moderate DLB (“AscenD-LB”), neflamapimod demonstrated clinically meaningful improvement in cognition (DLB-specific Neuropsychological Test Battery) and function (Timed-Up-and-Go Test). Here, we provide the EEG results from this study.
Methods
Neflamapimod (40 mg) or placebo was administered BID or TID for 16 weeks. Task-free, eyes-closed EEG was performed at baseline and week 16. Due to COVID-19, week 16 EEG assessments were only available in 29 of 91 patients. Quantitative EEG analysis involved functional connectivity analysis in canonical frequency bands, more specifically the corrected Amplitude Envelope Correlation (AECc). 2-sided Wilcoxon Rank Sum Test p-values are reported.
Results
Overall, a consistent trend towards improved functional connectivity was found in the treated group. Mean AECc in the beta band (13-30 Hz) significantly increased with neflamapimod TID vs all placebo (p=0.033) and vs placebo TID (p=0.01). The effect was most prominent in the frontal region (p=0.009 for placebo TID vs neflamapimod TID), and in the lower beta range (13-20 Hz).
Conclusions
In this modest cohort size, neflamapimod shows a positive effect on beta band functional connectivity. The effect is dose-dependent and most pronounced in the 40mg TID dose group, which previously also showed the clinical effects. Since impaired functional connectivity in the beta band is a known and relatively specific DLB finding, these results imply functional recovery. A follow-up clinical study will explore the observed treatment effects on EEG in a larger cohort.