Marinus Pharma Shares Phase 3 RAISE Trial Data in Refractory Status Epilepticus at 2024 Neurocritical Care Meeting

Marinus Pharmaceuticals, Inc., a company focused on developing treatments for seizure disorders, has unveiled new findings from its Phase 3 RAISE trial. This study examines the effectiveness of intravenous (IV) ganaxolone in treating refractory status epilepticus (RSE), a severe and persistent form of seizure. The data was shared at the Neurocritical Care Society (NCS) Annual Meeting.

The RAISE trial (NCT04391569) involved patients with RSE who had not responded to at least two antiseizure medications. Participants were randomly assigned to receive either IV ganaxolone or a placebo, along with the standard of care treatment. The trial's co-primary objectives were assessing the percentage of patients achieving cessation of status epilepticus (SE) within 30 minutes, and the percentage of patients avoiding progression to IV anesthesia within 36 hours of starting the trial drug.

Key secondary outcomes presented at the NCS meeting included:
- Median time to SE cessation: 4.2 minutes for patients treated with IV ganaxolone, compared to 307.2 minutes for those on placebo (nominal p<0.0001).
- Proportion of patients experiencing no treatment escalation within 24 hours: 45% for IV ganaxolone versus 19% for placebo (nominal p=0.0059).

Previously reported results from the RAISE trial showed:
- A significant percentage of patients reached SE cessation within 30 minutes of IV ganaxolone initiation compared to placebo: 80% vs. 13% respectively (p<0.0001).
- However, the trial did not achieve statistical significance for the second co-primary endpoint, with 63% of IV ganaxolone patients not progressing to IV anesthesia within 36 hours versus 51% for placebo (p=0.162).
- Median reduction in EEG seizure burden over 36 hours was 93% for IV ganaxolone patients, compared to 36% for placebo (nominal p=0.003).

The occurrence of serious adverse events was similar between the two groups, although hypotension was more frequent in the IV ganaxolone group.

Dr. Brandon Foreman, who presented the data, emphasized that IV ganaxolone showed promising rapid seizure cessation and significant EEG seizure control. Though the trial did not meet the second co-primary endpoint, secondary measures indicated meaningful clinical benefits.

Dr. Joseph Hulihan, Chief Medical Officer at Marinus, highlighted the importance of these findings in advancing the treatment of RSE. He noted that the first placebo-controlled trial in RSE has provided valuable insights and expressed eagerness to discuss the results with the FDA and plan the next steps for IV ganaxolone.

Ganaxolone's development in the RAISE trial was partly supported by the Department of Health and Human Services and the Biomedical Advanced Research and Development Authority (BARDA).

Status epilepticus (SE) is a critical condition marked by prolonged seizures due to failed termination mechanisms or triggered by mechanisms that prolong seizures. It is a common neurological emergency in the U.S., affecting up to 150,000 individuals annually, and is associated with significant morbidity, mortality, and healthcare costs. Patients unresponsive to first- and second-line treatments, such as benzodiazepines and IV antiseizure medications, are categorized as having RSE.

IV ganaxolone, a neuroactive steroid, modulates GABAA receptors to enhance inhibitory signaling. It has received orphan drug designation from the U.S. FDA for potential SE treatment. Marinus Pharmaceuticals, a company focused on innovative seizure disorder therapies, introduced its FDA-approved product ZTALMY® (ganaxolone) oral suspension CV in the U.S. in 2022.