Marinus Pharmaceuticals, Inc. (MRNS), announced positive preliminary data from the initial CDKL5 patients enrolled in its ongoing Phase 2 open-label study evaluating its CNS-selective GABAA modulator, ganaxolone, as a treatment for orphan, genetic disorders. CDKL5 is a severe, rare genetic disorder that results in early-onset, difficult-to-control seizures, and neuro-developmental impairment. Enrollment is continuing in the study with top-line data expected in mid-2017.
Four patients have been enrolled in this cohort of the study and received up to 1800 mg/kg of ganaxolone per day for an average treatment duration of five-months. Three of the four patients experienced a notable reduction in seizure frequency compared to baseline ranging from 52% to 88%. All responders continue to receive treatment, two of whom have completed six-months of treatment and have elected to participate in the study extension. One patient discontinued the study after four-months of treatment due to lack of efficacy. Safety data to date are consistent with earlier studies where ganaxolone has shown to be generally safe and well-tolerated.
“We are encouraged by the results in these difficult-to-treat pediatric patients,” commented Dr. Jaakko Lappalainen, Vice President of Clinical Development of Marinus Pharmaceuticals. “Concurrent with completing this study, we will be evaluating the potential for breakthrough therapy and applying for orphan drug designation with the United States Food and Drug Administration. CDKL5 pediatric epilepsy may prove to be an attractive and efficient path for ganaxolone and we look forward to evaluating results from the final patients enrolled in this cohort of the study.”
Michael G. Chez, MD, Director of Pediatric Neurology Research and Pediatric Epilepsy, Sutter Neuroscience Institute in Sacramento, CA commented, “I am impressed with the responder rate and magnitude of seizure control seen with ganaxolone in the initial CDKL5 patients. The CGIs (clinical global impression scales) are consistent with seizure control, with responders showing ‘much improved’ under this scale. I look forward to further evaluating these children and seeing the final results.”
At the annual meeting of the American Epilepsy Society, Dr. Chez presented EEG data from one CDKL5 and two PCDH19 patients that he treated with ganaxolone in the on-going Phase 2 open-label study. The patients received up to 1800 mg/day of ganaxolone. EEG measurements were taken at baseline and followed-up at 8-12 weeks of treatment.
The CDKL5 patient showed a >67% seizure reduction and EEG changes consistent with clinical improvement (50% reduction in awake slow-spike wave discharges). The two patients with PCDH19 showed an 80% and 75% reduction in seizure frequency, respectively, and EEG improvement in slow-spike and wave frequency of >90% and 80% on awake and asleep EEG.
This Phase 2 open-label trial is currently accepting patients at five sites in the United States and one in Italy. The multi-cohort study is designed to enroll up to 10 patients with each of CDKL5 disorder, Lennox Gastaut Syndrome (LGS) and PCDH19 pediatric epilepsy. The study is actively recruiting CDKL5 and LGS patients. The PCDH19 cohort of the study is currently closed for enrollment, however, there are still children receiving ganaxolone in the study extension
Filed Under: Drug Discovery
