Cassava Sciences, Inc. reported top-line results from a Phase IIb study of PTI 125, its lead investigational drug, in patients with Alzheimer’s disease. This study did not meet its primary endpoint. The pre-specified primary endpoint was a statistically significant effect of PTI 125 versus placebo on cerebrospinal fluid (CSF) levels of tau protein and other biomarker assessments from baseline to Day 28.
PTI 125 significantly reduced a secondary endpoint, CSF levels of IL1-beta (p<0.035), a core biomarker of neuroinflammation, from baseline to Day 28. Drug was safe and well-tolerated.
A post-hoc analysis of biomarker data revealed high variability in levels of CSF biomarkers over 28 days. For example, placebo-treated patients recorded changes in levels of CSF tau and p-tau ranging from -54% to +34% and -49% to +253%, respectively, from baseline to Day 28. Biomarker analysis was conducted by outside labs. The drug effects of PTI 125, if any, may have been masked in this study by high variability in levels of biomarkers of disease. In the months ahead the Company plans to re-analyze CSF biomarkers from all study participants.