Marinus Pharmaceuticals Experimental Epilepsy Treatment Shows Promise in Open-Label Extension Study
BRANFORD, Conn., Dec. 21, 2011
BRANFORD, Conn., Dec. 21, 2011 /PRNewswire/ -- Marinus Pharmaceuticals, Inc., a specialty pharmaceutical company, today announced that its neurosteroid ganaxolone which is currently under study for the treatment of partial onset seizures (POS), reported positive data in the open-label extension follow up to the company's Phase 2 clinical trial. The data reflects the replication of the effects seen in the double-blind study. Patients who enrolled in the study demonstrated an overall decrease of 23.2% in median weekly seizure frequency (MWSF) from baseline of the Phase 2 study. The data were presented at the 65th Annual Meeting of the American Epilepsy Society (AES) in early December.
In the 2 year open-label extension to the double-blind Phase 2 study, 123 subjects (94% of those eligible) took 1200-1500mg/day of ganaxolone for up to 2 years as add-on therapy. Common background epilepsy medications in the trial were lamotrigine, levetiracetam, carbamazepine and topiramate.
Efficacy was measured as the change in MWSF from baseline of the Phase 2 study to endpoint of the open-label study. Overall, there was a decrease of 23.2% in MWSF during the trial, and subjects (n=43) who had been on placebo in the double-blind study had a decrease in MWSF of 34.7%. Seventy percent of subjects had an improvement in their seizures during the study, and 24% had an improvement of 50% or more compared to baseline of the double-blind study.
Ganaxolone modulates GABA-A ion channels by selectively binding to neurosteroid receptor sites located on synaptic and extrasynaptic neurons, and differs mechanistically from currently approved antiepileptics. Marinus previously reported data from a double-blind, placebo-controlled US study of ganaxolone in 147 adults (98 GNX, 49 PBO) with refractory POS that demonstrates ganaxolone is efficacious, safe and well-tolerated compared to placebo when used as add-on therapy for up to 10 weeks in subjects who had epilepsy for an average of 25 years. Subjects in the study were taking up to 3 additional antiepileptic medications, and were experiencing an average of 9.5 seizures per month. At the end of the 10-week double-blind trial, those who received ganaxolone had improved 20% compared to those on placebo.
"The data from Study 601 provides evidence of the tolerability, safety and persisting efficacy of ganaxolone with long-term use as adjunctive therapy for partial seizures," said Gail Farfel, Ph.D., Chief Development Officer at Marinus. "Ganaxolone's mechanism differs from other approved antiepileptic agents, which is important when selecting adjunctive therapy."
Due to lack of resources during 2008-2009, the study was terminated prior to completion. Thirty percent of subjects completed 1 year of treatment and 5% completed two years. Ganaxolone was shown to be safe and well-tolerated during the extension study, and no new safety concerns were identified with extended use of the drug. The most common adverse events reported in the study were headache, seizures, fatigue, falls and bruises, dizziness, sore throat and nasal congestion. Ten subjects had serious adverse events that were not related to their epilepsy, and 11% of subjects in the study discontinued due to adverse events (most common: seizures 2.4%, dizziness 1.6% and fatigue 1.6%). No changes were seen in vital signs, blood chemistry or electrocardiogram to indicate any significant medical changes, and the median weight change from baseline to endpoint was less than one pound.
About Marinus Pharmaceuticals:
Founded in 2003, Marinus Pharmaceuticals is a privately held specialty pharmaceutical company located in Branford, Connecticut. Marinus is dedicated to the reformulation, development, and commercialization of ganaxolone to treat serious neurological and psychiatric disorders. Its lead candidate, Ganaxolone, is the most advanced neurosteroid in development for Epilepsy, Posttraumatic Stress Disorder and Fragile-X Syndrome.