Golexanolone shows promise in cirrhosis

In patients with cirrhosis, novel small molecule drug golexanolone is well-tolerated and seems to be effective at improving cognitive performance, a new pilot study has found.

The current study presented the results of the second to the fourth parts of a previously registered randomized, double-blinded, placebo-controlled trial. In brief, consenting and eligible cirrhotic patients were randomized to 3 weeks of golexanolone (10, 40, or 80 mg twice-daily) or placebo.

Outcomes were measured using the Psychometric Hepatic Encephalopathy Score (PHES), Animal Naming Test (ANT), Epworth Sleepiness Scale (ESS), continuous reaction time (CRT), and electroencephalography (EEG).

In the second part of the trial, researchers found no adverse events that led to study withdrawal. In the third part, eight treatment-emergent adverse events (TEAEs) were recorded, of which seven were mild; none were serious, and there were no related discontinuations. In the fourth and final parts of the trial, 15 patients reported 49 TEAEs.

In terms of efficacy, the researchers also noted significant and directionally favourable improvements in ESS (p=0.047) and EEG, particularly in the ratio of delta and theta frequencies to alpha and beta frequencies (p=0.021). There were also favourable but marginal improvements in the mean dominant frequency of EEG (p=0.143).

Improvements in cognitive measures such as CRT, PHES, and ANT were also detected, but failed to achieve significance.

“The findings therefore support a role for neurosteroids in the pathogenesis of hepatic encephalopathy-related sleepiness and vigilance in particular and indicate that golexanolone deserves further study as a potential treatment for neurosteroid-mediated vigilance and cognitive disorders including hepatic encephalopathy, either alone or in association with ammonia-lowering strategies,” the researchers said.