Marinus Pharmaceuticals announced positive results from the phase 3 MARIGOLD study, which evaluated oral ganaxolone in children and young adults with CDKL5 deficiency disorder (CDD), a rare, genetic epilepsy with refractory seizures. The primary endpoint of the trial was reached and ganaxolone was well tolerated. Regulatory submissions are planned for 2021.
The global, double-blind, placebo-controlled MARIGOLD trial enrolled 101 children and young adults ages 2 to 21 with a confirmed, disease-related CDKL5 gene variant. Following a 6-week baseline period, the patients were randomized to receive either oral ganaxolone (up to 1,800 mg/day) or placebo for 17 weeks, in addition to their existing anti-seizure treatment. Following the double-blind phase, patients were eligible to continue receiving ganaxolone in an open-label extension.
The primary efficacy endpoint was the percentage change in 28-day frequency of major motor seizures during the double-blind phase relative to the 6-week baseline period. Patients who received ganaxolone showed a significant 32.2 percent median reduction in 28-day major motor seizure frequency, compared to a 4.0 percent reduction for those receiving the placebo, achieving the primary endpoint. Numerical trends favoring ganaxolone were observed across several predefined secondary endpoints, however, ganaxolone did not meet statistical significance. Ganaxolone did meet statistical significance in exploratory secondary endpoints. Ganaxolone was generally well tolerated with a safety profile consistent with previous clinical studies. The most frequent adverse event was somnolence.
Top-line results from MARIGOLD will be presented at an upcoming scientific meeting.
Marinus plans to submit an NDA for ganaxolone to the U.S. FDA in mid-2021 and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) by the end of Q3 2021 in the treatment of CDD.
The FDA has granted Rare Pediatric Disease Designation to ganaxolone for CDD.
Ganaxolone, a positive allosteric modulator of GABAA receptors, is being developed in intravenous and oral formulations intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Unlike benzodiazepines, ganaxolone exhibits antiseizure, antidepressant and anti-anxiety activity via its effects on synaptic and extrasynaptic GABAA receptors.
About CDKL5 Deficiency Disorder
CDKL5 deficiency disorder (CDD) is a serious and rare genetic disorder that is caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome. CDD is characterized by early-onset, difficult-to-control seizures and severe neuro-developmental impairment. Most children affected by CDD cannot walk, talk, or feed themselves. Currently, there are no therapies approved specifically for CDD.