Abstracts

Rationale: Rationale: Ganaxolone (GNX), a synthetic analog of the endogenous GABA modulator allopregnanolone, is a first-in-class neurosteroid in development for treatment of epilepsy and other neurological and psychiatric conditions. GNX 1500mg/day has been shown as safe and effective for the treatment of epilepsy in a 10 week, double-blind (DB), placebo (PBO)-controlled study of GNX as adjunctive therapy in adult outpatients with uncontrolled partial onset seizures (POS). Additional responder analyses was performed on this study to evaluate the response rates across the study population.Methods: In Study 1042-0600, 147 subjects aged 18-69 years of age with a diagnosis of epilepsy consisting of uncontrolled partial-onset seizures (POS), with or without secondary generalization despite being treated with up to 3 AEDs, were randomized in a 2:1 ratio to receive placebo or ganaxolone oral suspension (50 mg/mL) as add-on therapy for up to 10 weeks at multiple centers in the United States. A secondary efficacy measure was the proportion of subjects who achieved at least a 50% reduction in seizure frequency compared to baseline, during Maintenance period (8 weeks). Post-hoc, we compared treatments in terms of the proportion of responders who achieved >50%, >40% and > 30% reduction over baseline. There was no adjustment for multiplicity.Results: The percentage of responders who achieved >50% improvement was numerically greater, in the GNX (26.3%) vs the PBO group (13%), and the difference just missed statistical significance (P=0.057.) The percentage of ganaxolone treated patients who achieved at least a 40% (30.5%) improvement was nearly twice that of the placebo group (16.7%,), which was also nearly significant (p=0.07). Significantly more GNX subjects (43.9% achieved >30% improvement over PBO subjects (25.0%; P= 0.0270).Conclusions: The standard-of-care for epilepsy has improved over the past decade with the number of new AEDs approved. This is reflected in the overall decrease in the incremental seizure improvement in the treatment resistant epilepsy population as new drugs are introduced. Despite this shift, this post-hoc analysis showed that adjunct treatment with GNX resulted in nearly twice as many subjects meeting 50% and 40% responder criteria and significantly more subjects meeting 30% responder criteria over placebo-treated subjects.