Authors :
Presenting Author: Maciej Gasior, MD, PhD – Marinus Pharmaceuticals, Inc.
Alex Aimetti, PhD – Marinus Pharmaceuticals, Inc.; Joseph Hulihan, MD – Marinus Pharmaceuticals, Inc.; Lisa Alvarez, PharmD – Marinus Pharmaceuticals, Inc.
Rationale:
Ganaxolone (GNX), a neuroactive steroid and positive allosteric modulator that targets both synaptic and extrasynaptic GABAA receptors, is FDA-approved for the treatment of seizures associated with CDD in patients ≥2 years old. GNX is administered as an oral suspension, however ~20% of patients with CDD are fed exclusively by gastrostomy (g-tube) or nasogastric tubes (Olson 2019). We conducted a subgroup analysis of GNX safety and efficacy data in patients with feeding tubes during the Phase 3 Marigold study (NCT03572933).Methods:
In the international, randomized, double-blind (DB), placebo-controlled Marigold study of patients with CDD treated with adjunctive GNX, 17/101 patients were administered drug via g-tube. Ten patients received GNX three times per day (TID), and seven patients received placebo. Reduction in major motor seizure frequency (MMSF), occurrence of treatment-emergent adverse events (TEAEs), plasma GNX concentrations, and discontinuations were analyzed.Results:
During the DB phase, the median (95% CI) change in MMSF from baseline in g-tube fed patients was -10.17% (-28.73, 39.66) for the placebo group (n=7) and -21.98% (-40.89, -5.71) for the GNX group (n=10). In patients without a g-tube, the change in MMSF was -4.20% (-18.32, 16.14) for the placebo group (n=44) and -30.66% (-42.10, -3.28) for the GNX group (n=39). Plasma GNX levels for patients who were administered drug via a g-tube were generally comparable to patients who were taking GNX without a g-tube. With or without a g-tube, the type, frequency, and severity of TEAEs were similar. The majority of TEAEs were mild or moderate; there were no severe events. Conclusions:
Based on data from the Phase 3 study, the efficacy, safety, and drug exposure appear similar between patients administered GNX orally and via g-tube.
Olson et al. Pediatr Neurol. 2019;97:18-25.
Funding:
Marinus Pharmaceuticals, Inc.