Probiodrug reports Phase IIa data for glutaminyl cyclase inhibitor in early AD

Probiodrug AG (Euronext:PBD) reported data from the Phase IIa SAPHIR trial in 120 patients with early Alzheimer's disease (AD) showing that there was no significant difference between patients who received twice-daily 800 mg oral PQ912 for 12 weeks or placebo in the rate of adverse events and serious adverse events. PQ912 did lead to a significantly higher discontinuation rate due to serious adverse events or grade 3 adverse events compared to placebo (p=0.027). The trial's primary endpoint is safety.

On secondary endpoints, PQ912 reduced pyroglutamate beta amyloid oligomers in CSF compared to an increase in the placebo arm. Additionally, PQ912 non-significantly reduced levels of neurogranin, a marker of synaptic dysfunction, and chitinase 3-like 1 cartilage glycoprotein-39 (CHI3L1; YKL40), a biomarker of inflammation, vs. placebo (p=0.1 and p=0.07, respectively). Probiodrug said that by excluding 3 patients who started prohibited concomitant medication during the trial, the reduction with PQ912 in neurogranin levels became significant compared to placebo (p=0.046). PQ912 also significantly reduced theta power as measured by EEG vs. placebo (p=0.002). The company said slow wave theta activity has been reported to increase with the onset and progression of AD. Furthermore, PQ912 significantly improved performance on the One Card Back Test working memory assessment vs. placebo (p=0.05) and non-significantly improved the Detection Test attention assessment vs. placebo...