ZTALMY (ganaxolone) - Epilepsy

The Committee deems that the clinical benefit of ZTALMY (ganaxolone) is moderate in the adjunctive treatment of epileptic seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients 2 to 17 years of age, only in the event of drug-resistant epilepsy.

Considering:

• demonstration of the superiority of ganaxolone compared to placebo, as adjunctive therapy, in a randomised, double-blind study, on a primary endpoint of variation in the frequency of major motor seizures in the short term (17 weeks), with a modest size effect (median difference of -27.08% in patients with a median number of 49 to 54 seizures per month at baseline), in a context of a high level of drug resistance,
• the substantial medical need to have access to alternatives, due to the limited alternatives in this rare disease,

but in view of:

• the absence of a demonstrated statistically significant difference compared to placebo for the percentage of patients presenting an at least 50% reduction in the number of seizures, a relevant ranked secondary endpoint,
• the absence of robust data on quality of life, which is particularly impacted in this disease,
• the absence of long-term efficacy and safety data for ganaxolone, in the context of a chronic disease,

the Committee considers that ZTALMY (ganaxolone) as adjunctive therapy provides no clinical added value (CAV V) in the treatment of drug-resistant seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients 2 to 17 years of age.