Status Epilepticus (SE)
SE is a medical emergency associated with significant morbidity and mortality. While there are no FDA approved treatments for SE, single or combinations of intravenous (IV) antiepileptic drugs (AEDs) are used to attempt to break the seizures.
We are developing ganaxolone IV for the hospital setting offering a new mechanism of action for SE patients who continue to experience seizures despite treatment with an AED, a clinical situation referred to as established status epilepticus (ESE). There are approximately 45,000 cases of hospitalized ESE treated in the United States annually. ESE patients who do not respond to additional AEDs are generally placed under IV anesthesia as a last resort to attempt to stop the seizures and prevent further damage to the brain and death. Those who do not respond to therapy and are placed in a medically induced coma and referred to as having super refractory status epilepticus (SRSE). Morbidity and mortality rates increase for patients that progress from ESE to SRSE.
Clinical Development for Ganaxolone in Status Epilepticus
Data from a Phase 1 dose-escalation study in 36 subjects showed that ganaxolone IV achieved dose levels targeted for efficacy in patients with SE. The study evaluated the pharmacokinetics, pharmacodynamics, and safety of ganaxolone IV administered as an ascending bolus dose or continuous infusion. Every dose regimen of ganaxolone IV administered was generally safe and well tolerated and reached targeted dose levels in a short period of time. Following treatment, six treatment-emergent adverse events were reported, all of which were mild in severity and resolved without intervention.
Data from preclinical studies, conducted at two separate laboratories using different measurements, yielded positive results testing ganaxolone IV in benzodiazepine-resistant SE. Ganaxolone IV promoted survival and showed better or comparable reversal of seizures than the endogenous neurosteroid allopregnanolone, in clinically translatable rodent models of SE.
Ganaxolone IV has received orphan drug designation from the U.S. Food and Drug Administration for the treatment of SE.