Marinus charts approval course after mixed seizure therapy results

Marinus Pharmaceuticals has announced its intention to engage with the FDA to discuss a potential future direction for the intravenous (IV) formulation of its anti-seizure drug, ganaxolone. This decision follows mixed results from a late-stage study involving patients with refractory status epilepticus (RSE). While the drug achieved one of its primary goals, it fell short on the other. The announcement comes two months after the Phase III RAISE trial's interim analysis failed to meet early stopping criteria, causing Marinus' stock to drop by over 80%. However, the latest data release did not further impact the stock, which remained stable.

Ganaxolone represents a significant part of Marinus' strategy, especially as the biotech firm faced financial constraints earlier this year. In May, Marinus reduced its workforce by approximately 20% and delayed some of its manufacturing investments to extend its financial runway until the second quarter of 2025 while awaiting the RAISE trial outcomes. The company expects full-year sales of the oral version of ganaxolone, branded as Ztalmy, to be between $33 million and $35 million. This version is used to treat seizures in patients with CDKL5 deficiency disorder, generating $7.5 million in revenue in the first quarter.

The RAISE trial included 96 RSE patients who had not responded to at least two previous anti-seizure treatments. Participants were randomly assigned to receive either IV ganaxolone or a placebo. Results showed that 80% of patients treated with ganaxolone achieved cessation of status epilepticus within 30 minutes, compared to 13% in the placebo group. This success marked the achievement of one of the study's co-primary endpoints. However, the drug missed the second co-primary endpoint, which measured the proportion of patients who avoided the need for IV anesthesia for 36 hours post-treatment. In this measure, 63% of the ganaxolone group did not progress to requiring IV anesthesia, compared to 51% in the placebo group, missing the statistical significance threshold.

Marinus' Chief Medical Officer, Joseph Hulihan, suggested that the failure to meet the second endpoint could be due to the treatment group having more severe cases than the placebo group. He pointed out that the ganaxolone group had a higher proportion of patients in stupor or coma, those requiring mechanical ventilation, and those with underlying disorders linked to higher morbidity and mortality rates, such as glioblastoma and encephalitis.

Additionally, the company indicated that the need for IV anesthesia might not be an accurate measure of seizure control. Preliminary electroencephalogram (EEG) analyses suggested other factors could have influenced the need for IV anesthesia apart from the severity of status epilepticus. According to EEG scans, patients treated with ganaxolone experienced an 88% median reduction in seizure burden over 36 hours, in contrast to a 38% reduction in the placebo group.

Marinus' future steps include detailed discussions with the FDA to chart a path forward for ganaxolone’s IV formulation. This move aims to advance the drug's development despite the mixed results, highlighting the company's commitment to addressing severe seizure disorders.