Marinus Pharmaceuticals, Inc., a pharmaceutical company dedicated to the development of innovative therapeutics to treat rare seizure disorders, announced it will host a virtual Scientific Exhibit at the American Epilepsy Society (AES) Annual Meeting (AES2020). At the Scientific Exhibit, Marinus will have 10 posters highlighting the company’s clinical development programs in treating CDKL5 deficiency disorder (CDD) and refractory status epilepticus (RSE).
Highlights from new analyses in the Phase 3 Marigold Study of ganaxolone in CDD presented during the Scientific Exhibit include the following:
“Effect of Ganaxolone on Seizure Frequency Across Subpopulations of Patients with CDKL5 Deficiency Disorder: Subgroup Analyses of the Marigold Study,” by E. M. Pestana-Knight, et al.
An analysis of data from the Marigold Study showed patients on ganaxolone consistently demonstrated numerical improvements in the change in major motor seizure frequency relative to placebo across the following subgroups: age, gender, baseline seizure frequency, number of concomitant antiepileptic drugs, geography and baseline allopregnanolone sulfate levels. These findings support ganaxolone’s effect across the broad CDD population studied. Data collected in patients enrolled in the United States (n=41) showed a stronger effect with a 36.7% estimated difference in major motor seizure frequency relative to placebo.
“Pharmacokinetic-Pharmacodynamic Analysis in Ganaxolone-Treated Patients with CDKL5 Deficiency Disorder: Results From the Marigold Study,” by J. Hulihan, et al.
Higher plasma ganaxolone concentrations were correlated with greater reductions in major motor seizure frequency. However, no differences in the rates of relevant adverse events were noted across ganaxolone plasma concentration groups. These findings highlight the importance of achieving adequate plasma ganaxolone concentrations and suggest that three times a day (TID) dosing has the potential to increase trough ganaxolone levels and may provide improved seizure control. In addition, this analysis supports efforts to develop new oral ganaxolone formulations that aim to improve pharmacokinetic properties to better achieve target ganaxolone exposure levels.
“Extended Duration Safety and Efficacy of Ganaxolone for the Treatment of CDKL5 Deficiency Disorder: Preliminary Open-Label Extension Analysis (Marigold Study),” by N. Specchio, et al.
Preliminary data from patients in the open-label extension phase of the Marigold Study as of September 2020 were summarized. Patients on ganaxolone in the double-blind phase continued to experience a maintained improvement in major motor seizure frequency through eight months in the open-label extension, representing approximately 12 months in total on ganaxolone. This group of patients treated with ganaxolone for 12 months (n=17) experienced a median 52.7% reduction in major motor seizure frequency relative to baseline.
Patients on placebo in the double-blind phase showed improvements in major motor seizure frequency when transitioning to open label ganaxolone. These preliminary findings suggest that ganaxolone has the potential to provide clinically meaningful, durable seizure improvements in patients with CDD.
The following posters were presented during the AES Scientific Sessions:
- “Ganaxolone Significantly Reduces Major Motor Seizures Associated with CDKL5 Deficiency Disorder: A Randomized, Double-blind, Placebo-Controlled Phase 3 Study (Marigold Study)”; E. M. Pestana-Knight, et al.
- “IV Ganaxolone in Pediatric Super-Refractory Status Epilepticus: A Single Patient Case Study”; R. Singh, et al.
- “Treatment of Super Refractory Status Epilepticus Using Intravenous Ganaxolone in a Patient with Lennox-Gastaut Syndrome and Angelman Syndrome”; M. G. Chez, J. Hulihan, and M. Gasior
- “Status Epilepticus: Inpatient Burden of Illness and Association with Disease Severity”; E. L. Guterman, et al.