Ganaxolone

Drug Overview

Marinus Pharmaceuticals is developing ganaxolone, a first-in-class synthetic neurosteroid drug for the adjunctive treatment of status epilepticus and pediatric orphan indications. It is a structural analog of the endogenous steroid allopregnanolone, and as such, is a powerful positive allosteric modulator of the gamma-aminobutyric acid (GABA)-A receptor with comparable potency.

In June 2016, Marinus Pharmaceuticals announced its plans to discontinue the development of ganaxolone for adult partial-onset seizures following its failure to meet the primary endpoint in a Phase III study (ClinicalTrials.gov identifier: NCT01963208). Marinus Pharmaceuticals plans to focus its efforts on advancing ganaxolone in status epilepticus and other pediatric niche indications.

Ganaxolone has orphan drug designation, both as an intravenous formulation for the treatment of status epilepticus and as a potential oral treatment for PCDH19 female epilepsy. Further clinical development in both of these indications is underway, in addition to a separate study in fragile X syndrome.

Analyst Outlook

Marinus Pharmaceuticals intends to continue the clinical development of ganaxolone in status epilepticus and pediatric orphan indications, despite the failure of the Phase III trial evaluating the efficacy of the drug in patients with refractory partial-onset seizures. Pediatric orphan indications, including PCDH19 female epilepsy, represent high unmet needs given the limited therapies available. While ganaxolone’s weak efficacy profile is not encouraging for its other niche indications under investigation, Datamonitor Healthcare believes that Marinus Pharmaceuticals is betting on the scientific rationale supporting use in PCDH19 female epilepsy.