American researchers have reported success in phase III clinical trials of ganaxolone for status epilepticus. The report was presented at the 22nd annual meeting of the International Society of Critical Care Medicine (NCS), and the results of the work are presented in a press release from the University of Cincinnati.
Status epilepticus is the most severe form of epilepsy, in which seizures continue uninterrupted. Even with medical care, it is fatal in 20–30 percent of patients. Survivors often have cognitive dysfunction and disability, and a greatly increased risk of recurrent seizures. Ganaxolone is a synthetic neurosteroid that acts as a positive allosteric modulator of GABA receptors. It is approved in the United States for seizures due to CDKL5 deficiency syndrome and has orphan drug status.
Brandon Foreman of the University of Cincinnati and colleagues conducted the multicenter, double-blind, randomized, phase III RAISE trial. They enrolled 124 patients aged 12 years and older whose seizures had progressed to refractory status epilepticus despite receiving at least two anticonvulsants, including a benzodiazepine. In such situations, people are put into a drug-induced coma, but in the trial they were given either an intravenous bolus dose of ganaxolone, followed by a maintenance infusion for three days and tapered over 12 hours, or a placebo.
In 80 percent of patients receiving the active drug, seizures ceased within 30 minutes (the primary endpoint), with a median time to cessation of four minutes. With placebo, seizure control within half an hour was achieved in 13 percent of participants, with a median duration of seizures of five hours. The secondary endpoint of avoiding the need for anesthesia for 36 hours was not achieved: this intervention was not required in 63 percent of patients in the main group and 51 percent in the control group, a difference that was not statistically significant.
Moreover, in the first 24 hours after the placebo was prescribed, 81 percent of the participants needed additional medications (anticonvulsants or intravenous general anesthesia) versus 55 percent when using the active substance. According to electroencephalography, the level of seizures decreased by 93 percent in the main group and by 36 percent in the control group. The frequency of serious adverse events did not differ significantly between the groups (this is largely due to the critical nature of the disease itself and the side effects of the anesthesia prescribed in case of ineffective treatment); arterial hypotension was most often observed when the active drug was administered.
Based on the results of the trials, the researchers found ganaxolone to be significantly effective and quite safe for refractory status epilepticus. Given that there are currently no approved drugs specific to this condition and the frequent side effects of anesthesia with intubation, ganaxolone may fill this niche, but the final decision remains with the FDA, the authors conclude.
Previously, American, Dutch and Polish researchers conducted clinical trials and concluded that a cannabidiol-based drug reduces the frequency of seizures in a severe form of epilepsy associated with Lennox-Gastaut syndrome. Six months later, the FDA approved this drug for use in two rare forms of epilepsy.