Marinus:RAISE didn’t achieve statistical significance on one endpoint

Marinus Pharmaceuticals announced topline results from the Phase 3 double-blind, randomized, placebo-controlled RAISE trial NCT04391569 evaluating the safety and efficacy of intravenous IV ganaxolone for the treatment of refractory status epilepticus RSE . RSE, in which prolonged continuous or rapidly recurring seizures do not respond to first- and second-line therapy, is associated with significant morbidity and mortality. 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: 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 . 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 . “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 3 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.” 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.”