Marinus Pharma Reports Phase 3 RAISE Trial Results for IV Ganaxolone in Refractory Status Epilepticus

Marinus Pharmaceuticals, Inc., a company committed to developing innovative treatments for seizure disorders, has reported results from its Phase 3 RAISE trial. This study evaluates the effectiveness and safety of intravenous (IV) ganaxolone in treating refractory status epilepticus (RSE). RSE is characterized by prolonged or rapidly recurring seizures unresponsive to initial treatments and is associated with high morbidity and mortality rates.

In the RAISE trial, patients with RSE who did not respond to at least two antiseizure medications were randomized to receive either IV ganaxolone or a placebo alongside standard care. The study included 96 patients, with 49 receiving IV ganaxolone and 47 on placebo.

Key findings from the trial include:
- The trial successfully met its first co-primary endpoint, with a significant proportion of patients achieving cessation of status epilepticus within 30 minutes of starting IV ganaxolone compared to placebo (80% vs. 13%, p<0.0001).
- The second co-primary endpoint was not met. The trial did not show a statistically significant difference in the proportion of patients avoiding progression to IV anesthesia within 36 hours (63% for ganaxolone vs. 51% for placebo, p=0.162).
- Serious adverse events were similar between the treatment and placebo groups, although hypotension was more common in the IV ganaxolone group.

Dr. Scott Braunstein, CEO of Marinus, acknowledged the mixed results but emphasized the valuable insights gained from the trial. Dr. Joseph Hulihan, Chief Medical Officer, highlighted the complexity of RSE and noted an imbalance in baseline characteristics between the treatment groups, potentially affecting outcome assessments.

Despite not achieving statistical significance in the second co-primary endpoint, Marinus believes IV ganaxolone shows promise in treating RSE. Preliminary EEG analyses suggest that patients receiving IV ganaxolone had a durable reduction in seizure burden, indicating effective control of status epilepticus. This was evident through an 88% median reduction in seizures for the ganaxolone group compared to 38% for the placebo group over 36 hours.

Dr. Aatif M. Husain from Duke University Medical Center stressed the importance of rapid seizure cessation to reduce the risk of permanent neurological damage. He also suggested that future trials incorporate objective measures like EEG to assess seizure control more accurately.

Marinus plans to continue analyzing the full RAISE dataset and will engage with the U.S. Food and Drug Administration (FDA) to discuss future steps for IV ganaxolone in treating RSE. The company intends to present the trial data at an upcoming medical conference and will continue offering IV ganaxolone for super refractory status epilepticus under emergency investigational new drug applications.

Financially, Marinus projects that its cash reserves, bolstered by recent cost reduction initiatives and financing activities, will support operations into the second quarter of 2025. The development of ganaxolone in the RAISE trial was partly funded by the Department of Health and Human Services and the Biomedical Advanced Research and Development Authority (BARDA).

Marinus Pharmaceuticals is dedicated to developing innovative treatments for seizure disorders and introduced its FDA-approved medication ZTALMY® (ganaxolone) oral suspension in 2022. The company continues to explore expansion opportunities in treating highly refractory, chronic epilepsies, with key data from the Phase 3 TrustTSC trial expected in early Q4 2024.