It has previously been announced that 100% of participants (n = 17) in a phase 2 open-label dose-finding trial treated with any of the 3 intravenous doses of ganaxolone used (500 mg/day, 650 mg/day, or 713 mg/day) did not progress to requiring intravenous anesthetics within 24 hours of receiving ganaxolone. Additional long-term data, presented at the American Epilepsy Society on December 6, 2019 in Baltimore, MD demonstrate all participants in the target-dose (713 mg/day) cohort who could be evaluated (n=6) had no relapse of status epilepticus during a 4-week follow-up period.
Ganaxolone was effective regardless of prior AED treatment and across diverse disease etiologies for RSE. Independent central review of seizure EEG data as an objective diagnostic tool showed a dose effect with the target level sustaining reductions more than 80% reductions in seizure burden throughout the analysis window.
Eugene Ramsay, MD, director emeritus, Ochsner Comprehensive Epilepsy Center in New Orleans, and investigator in the study said, “The expanded data set. . . bolsters our confidence that ganaxolone has the potential to establish a new treatment paradigm for RSE, a life-threatening condition with no approved treatments. . . Ganaxolone provided rapid onset of efficacy, the effect of ganaxolone was sustained, and dose specific, with no relapses observed in those patients who received the target dose and who were followed for 4 weeks. . . These data demonstrate that ganaxolone has the potential to revolutionize the treatment of status.”
“We believe that the expanded data from this phase 2 study are highly compelling and demonstrate the ability of ganaxolone to rapidly break status, maintain seizure control, and prevent progression to IV anesthetics across a diverse and severe patient population,” said Scott Braunstein, MD, chief executive officer of Marinus. “. . .we are confident that we have identified an optimized target dose for future studies that balances safety, efficacy and durability of responses. We are on-track for an end of phase 2 meeting with the FDA in the first quarter of 2020 and look forward to rapidly advancing this promising program to a potentially registration enabling study.”
In this study, participants who had failed a mean 2.1 second-line intravenous antiseizure medications (ASMs) at therapeutically relevant doses (all had received and not responded to both levetiracetam and lacosamide). All prior ASMs were given at therapeutically relevant doses, administered within recommended dosing guidelines and mean time since addition of most recent ASM was 4 hours. Ganaxolone was administered for up to 96 hours followed by a taper.
A single person in the target dose cohort had status relapse at day 1, which resolved during the ganaxolone infusion without treatment escalation and 1 person discontinued early because of severe sedation on day 1. A single person died from bowel perforation 9 days after ganaxolone discontinuation, which was not considered drug related. In the medium dose cohort, a single person experienced status relapse at day 2 during taper, and 1 person discontinued on day 3 because of severe sedation. In the low dose cohort, 2 people escalated to 3rd line therapy for seizure relapse at day 3 (1 of whom died 16 days after ganaxolone discontinuation after life-support withdrawal) and 1 participant died 22 days after ganaxolone discontinuation from sepsis. No deaths were considered drug related.
Jakai D. Nolan, DO, MPH, and Jacqueline A. Nicholas, MD, MPH
Bettina Balint, MD
Danielle S. Shpiner, MD; Crystal Dixon, MD; Melissa R. Ortega, MD; and Henry Moore, MD