American researchers reported success in a phase III clinical trial of ganaxolone for status epilepticus. The report was presented at the 22nd annual meeting of the International Critical Care Society (NCS), and the results were published in a press release from the University of Cincinnati.
Status epilepticus is the most severe form of epilepsy, characterized by continuous seizures. Even with medical treatment, it results in death in 20–30 percent of patients. Survivors often experience cognitive dysfunction and disability, as well as a significantly 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 associated with CDKL5 deficiency syndrome and has orphan drug designation.
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, patients are typically placed in a medically induced coma, but in the trial, they were initially given 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 seizure duration of five hours. The secondary endpoint—avoiding the need for anesthesia for 36 hours—was not met: 63 percent of patients in the main group and 51 percent in the control group did not require this intervention; the difference was statistically insignificant.
Moreover, in the first 24 hours after placebo administration, 81 percent of participants required additional medications (anticonvulsants or intravenous general anesthesia) versus 55 percent with the active substance. According to electroencephalography, the seizure rate decreased by 93 percent in the study group and by 36 percent in the control group. The incidence of serious adverse events did not differ significantly between groups (this is largely due to the critical nature of the disease itself and the side effects of the anesthetic administered in the event of treatment failure); arterial hypotension was most commonly observed with the active substance.
Based on the trial results, the researchers found ganaxolone to be significantly effective and completely safe for refractory status epilepticus. Given the current lack of approved medications specifically for this condition and the frequent side effects of anesthesia and intubation, ganaxolone could fill this niche, but the final decision remains with the FDA, the study's 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.
