Marinus Pharmaceuticals has announced positive results from its Phase III RAISE trial, evaluating intravenous (IV) ganaxolone for the treatment of refractory status epilepticus (RSE). The trial, a randomized, double-blind, placebo-controlled study, met one of its two co-primary endpoints, demonstrating a statistically significant improvement in seizure cessation within 30 minutes in patients treated with IV ganaxolone compared to placebo.
The RAISE trial enrolled patients with RSE who had failed at least two prior antiseizure medications. Participants were randomized to receive either IV ganaxolone or placebo in addition to standard of care. The co-primary endpoints were the proportion of patients with status epilepticus (SE) cessation within 30 minutes and the proportion of patients not progressing to IV anesthesia within 36 hours of study drug initiation.
Key Findings from the RAISE Trial
The study revealed that 80% of patients receiving IV ganaxolone achieved SE cessation within 30 minutes, compared to only 13% in the placebo group (p<0.0001). However, the trial did not meet its second co-primary endpoint, as there was no statistically significant difference in the proportion of patients not progressing to IV anesthesia within 36 hours (63% for ganaxolone vs. 51% for placebo, p=0.162).
Additional secondary endpoint results highlighted at the Neurocritical Care Society (NCS) Annual Meeting included:
- A median time to SE cessation of 4.2 minutes for ganaxolone-treated patients compared to 307.2 minutes for those on placebo (nominal p<0.0001).
- 45% of patients on IV ganaxolone experienced no escalation of treatment within 24 hours, compared to 19% for placebo (nominal p=0.0059).
- A median reduction in EEG seizure burden of 93% in the ganaxolone group, compared to 36% for placebo (nominal p=0.003).
Safety and Tolerability
The incidence of serious adverse events was similar between the treatment and placebo arms (n=19 for IV ganaxolone, n=18 for placebo), with hypotension being more commonly observed in the IV ganaxolone arm.
Expert Commentary
Brandon Foreman, M.D., M.S., FACNS, FNCS, Associate Professor of Neurology & Rehabilitation Medicine and Neurosurgery at the University of Cincinnati, who presented the RAISE data, stated, "With 80% of patients achieving SE cessation within 30 minutes of IV ganaxolone administration and a median time to SE cessation of 4.2 minutes, there is clear indication of rapid antiseizure activity in highly refractory patients."
Joseph Hulihan, M.D., Chief Medical Officer of Marinus, added, "The findings we shared today underscore the potential of IV ganaxolone in the management of RSE, while also highlighting the challenges inherent in advancing research in this highly variable, complex disorder. We have completed the first placebo-controlled trial in RSE, which has yielded important insights into the benefit ganaxolone could provide to these critically ill patients. We look forward to reviewing our data package with the FDA and discussing next steps for IV ganaxolone."
Implications for RSE Treatment
Status epilepticus (SE) is a life-threatening condition affecting up to 150,000 patients annually in the U.S. Refractory status epilepticus (RSE) occurs when patients do not respond to first- and second-line treatments. There are currently no FDA-approved medications specifically for RSE, and current treatment options beyond intubation and anesthetic medications are limited if standard antiseizure medications fail.
Ganaxolone, a neuroactive steroid that modulates GABAA receptors, has the potential to fill a critical gap in the treatment of RSE. The RAISE trial results suggest that IV ganaxolone could offer a rapidly effective medication to control seizures and potentially reduce the need for prolonged intensive care and anesthetic use, which are associated with increased morbidity and mortality.
