Ganaxolone drip safe, affords seizure control in patients with refractory status epilepticus

Treatment with intravenous (IV) ganaxolone induces rapid and durable seizure control in patients with refractory status epilepticus (SE), while showing acceptable safety and tolerability, according to the results of an open-label phase II trial.

The trial randomized 17 SE patients aged ≥12 years (mean age 56.9 years, 53 percent female), to receive IV ganaxolone at either 500 mg/day (low dose, n=5), 650 mg/day (medium dose, n=4), or 713 mg/day (high dose, n=8) as an add-on to standard-of-care antiseizure medications (ASMs). The infusion was initiated as an IV bolus (over 3 minutes) with continuous infusion of decreasing rates for 48–96 hours followed by an 18-hour taper.

SE was caused by various conditions, including brain tumours, stroke, neurodegenerative disorder, alcohol withdrawal, illicit drug use, metabolic disturbance, infection, autoimmune disorder, and others. About 50 percent of the population had a history of a seizure or epilepsy, 65 percent of patients had nonconvulsive SE, and one (6 percent) progressed from convulsive to nonconvulsive SE. The population had failed a median three prior ASMs, including first-line benzodiazepines and second-line IV ASMs. 

None of the patients across the three dose groups required escalation to IV anaesthetic treatment within 24 hours of ganaxolone initiation, the primary study outcome. Median time to SE cessation following ganaxolone initiation was 5 minutes.

In terms of safety, two treatment-related serious adverse events (sedation) were documented. There were three patients who died during the study, but none of the deaths was considered related to ganaxolone. All cases occurred 9–22 days after completing ganaxolone.

The findings highlight the potential of ganaxolone in the treatment of patients with refractory SE, as well as warrant further investigation of ganaxolone.