Topline results from phase III RAISE trial of i.v. ganaxolone in refractory status epilepticus

In the RAISE trial, patients with RSE that failed at least two antiseizure medications were randomized to IV ganaxolone or placebo in addition to standard of care treatment. The intent-to-treat population consisted of 96 patients, including 49 in the IV ganaxolone arm and 47 in the placebo arm. Topline data demonstrated that: i. The trial met the first co-primary endpoint: A statistically significant proportion of patients had status epilepticus cessation within 30 minutes of initiating IV ganaxolone compared to placebo: 80% vs. 13%, respectively (p<0.0001). ii. the trial did not meet the second co-primary endpoint: raise failed to achieve statistical significance in the proportion of patients not progressing to iv anesthesia for 36 hours following initiation of iv ganaxolone compared to placebo: 63% vs. 51%, respectively (p="0.162)." iii. 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 seen in the iv ganaxolone arm.

“Although the RAISE trial did not achieve statistical significance on one of its co-primary endpoints, these findings provide valuable insights that will guide our ongoing research and development in our mission to bring innovative and effective treatment options to those in need,” said Scott Braunstein, M.D., Chairman and Chief Executive Officer of Marinus. “We would like to thank the patients, families, investigators and their clinical trial sites for their contributions to this important research.”

Joseph Hulihan, M.D., Chief Medical Officer of Marinus commented, “We are proud to have conducted the first randomized Phase III trial in patients with refractory status epilepticus, a highly variable and complex seizure disorder. We noted that patients were enrolled late in their course of status, with study drug initiated, on average, 38 hours following onset. This appears to be inconsistent with the urgency to initiate therapy emphasized in treatment guidelines.”

Dr. Hulihan added, “Also disappointing to us was the imbalance in baseline characteristics between the two treatment arms, with a higher proportion of patients in the IV ganaxolone arm presenting with stupor or coma, entering the trial on mechanical ventilation, having a higher baseline status epilepticus severity score, and higher incidences of underlying disorders associated with significant morbidity and mortality, such as glioblastoma and encephalitis. We believe this imbalance confounds the assessment of potential differences in patient outcomes for IV ganaxolone compared to placebo.”

Marinus continues to believe in the potential of IV ganaxolone as a treatment for RSE, supported not only by the rapid onset of its antiseizure effect but also the objective evidence of status epilepticus control observed with an additional analyses of continuous electroencephalogram (EEG) monitoring. Preliminary EEG analyses indicate patients receiving IV ganaxolone demonstrated durable reductions in seizure burden through 36 hours with an 88% median reduction compared to 38% for placebo. This suggests that the need for IV anesthesia was driven by factors other than status severity and may not represent an accurate measure of seizure control.

“Stopping status epilepticus as quickly as possible is critical, as each passing minute heightens the risk of permanent neurologic impairment,” said Aatif M. Husain, M.D., Epileptologist, Neurologist, Professor in the Department of Neurology, and Chief of the Division of Epilepsy, Sleep, and Clinical Neurophysiology at Duke University Medical Center. “The findings in the RAISE trial indicate that objective measures such as EEG should be considered in future trials to assess control of status epilepticus rather than endpoints dependent on a proxy measure such as use of IV anesthesia.”

The Company will continue to analyze the full RAISE dataset and plans to engage with the FDA to discuss a potential path forward for IV ganaxolone in RSE. Marinus expects to present the RAISE data at an upcoming medical meeting. Marinus intends to continue to offer IV ganaxolone for patients with super refractory status epilepticus under emergency investigational new drug applications.

The Company expects cash and cash equivalents are sufficient to fund its operating expenses, including capital expenditure and working capital requirements, into the second quarter of 2025. The projection includes the impact of cost reduction plans announced earlier this quarter and recent amendments to Marinus’ existing credit agreement with Oaktree Fund Administration, LLC, and Marinus’ Revenue Interest Financing Agreement with Sagard Healthcare Royalty Partners, LP.

Ganaxolone development in the RAISE trial has been supported in part by the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA) under contract number 75A50120C00159.