Novel drug golexanolone shows promise against cognitive decline in hepatic encephalopathy

Golexanolone, a novel, small molecule, GABA-A receptor-modulating steroid antagonist, helps ease cognitive problems in patients with covert hepatic encephalopathy (HE) with no alarming safety signals, a recent study has found.

The study included 45 adult HE patients who were randomly assigned to receive 3 weeks of golexanolone (10, 40, or 80 mg doses, twice-daily) or placebo. Patients were eligible if they had Child-Pugh A/B cirrhosis and abnormal continuous reaction time (CRT) on screening.

Neuropsychiatric status was measured using the CRT, animal naming test (ANT), psychometric hepatic encephalopathy score (PHES), and Epworth Sleepiness Scale (ESS), along with an electroencephalogram. Assessments were done at baseline, and at 10 and 21 days.

The intervention was relatively safe. In the initial safety assessment, eight treatment-emergent adverse events (TEAEs) were recorded in seven patients. Most were mild and none were serious or led to study withdrawal. In the efficacy experiments, 49 TEAEs developed in 15 patients, most of which were again mild. One patient experienced three serious AEs, which ultimately led to discontinuation. Diarrhoea, dyspepsia, and nausea were the TEAEs deemed possibly related to the drug.

In terms of overall efficacy, golexanolone correlated with significant improvements in ESS (p=0.047), as well as in the mean dominant frequency (p=0.142) and delta+theta/alpha+beta ratio (p=0.021) in electroencephalography. Directionally favourable changes were also reported for CRT, PHES, and ANT, though these failed to reach statistical significance.

“The results of this study suggest that golexanolone is well tolerated and may improve cognition, as reflected by measures of sleepiness, attention span and brain wave activity, paving the way for future larger studies of this promising experimental drug,” the researchers said.