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Ganaxolone reduces frequency of CDKL5 deficiency disorder-associated seizures

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Patients with CDKL5 deficiency disorder (CDD) had less frequent CDD-associated seizures when treated with an investigational neuroactive steroid, Ganaxolone, compared with placebo, according to the results of a phase 3 trial.

In the double-blind phase of this randomized, placebo-controlled, 101 patients between the ages of 2-21 years with a pathogenic or probably pathogenic CDKL5 variant and ≥16 major motor seizures per 28 days in each 4-week period of an 8-week historical period were randomly assigned to receive either ganaxolone (n = 50) or placebo (n = 51) for 17 weeks.

The primary endpoint, which was percentage change in median 28-day major motor seizure frequency from the baseline period to the 17-week double-blind phase was analyzed in a population of 100 patients due to 1 patient in the ganaxolone group not having seizure frequency recorded at baseline.

In the ganaxolone group and the placebo group, the median percentage change in 28-day major motor seizure frequency was 30.7% (IQR -49.5 to -1.9) and -6.9% (-24.1 to 39.7), respectively. The Hodges-Lehmann estimate of median difference in responses to ganaxolone versus placebo was -27.1% (95% CI -47.9 to – 9.6).

Treatment-emergent adverse events were reported in 86% of 50 patients in the ganaxolone group and in 88% of 51 patients in the placebo group. At least 10% of patients in the ganaxolone group experienced somnolence, pyrexia, and upper respiratory tract infections.

Six patients and 5 patients experienced serious adverse events in the ganaxolone group and placebo group, respectively. In the ganaxolone group, 2 (4%) patients discontinued the trial; in the placebo group, 4 (8%) patients discontinued. There were no deaths in the double-blind phase.

Knight EMP, Amin S, Bahi-Buisson N, et al; Marigold Trial Group. Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2022;21(5):417-427. doi: 10.1016/S1474-4422(22)00077-1. PMID: 35429480.