Ganaxolone

Ganaxolone is the 3β-methylated synthetic analog of allopregnanolone, a metabolite of progesterone. Ganaxolone belongs to a class of compounds referred to as neurosteroids. Endogenous neurosteroids, which comprise certain metabolites of progesterone and deoxycorticosterone, bind potently and specifically to GABA receptors to enhance their inhibitory effects, and are thus known to have anxiolytic, analgesic, anticonvulsant, sedative, hypnotic, and anesthetic properties.

Ganaxolone, similar to its endogenous counterparts, is a positive allosteric modulator of GABA receptors. It was approved under the brand name ZTALMY by the US FDA in March 2022 for the treatment of seizures associated with CDKL5 deficiency disorder (CDD), becoming the first FDA-approved treatment indicated specifically for CDD. In July 2023, ganaxolone was also approved under the same brand name and for the same indication by the EMA.

Ganaxolone is indicated for the treatment of seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients ≥2 years old by the FDA. It is also approved as an adjuvant treatment for the same condition in patients aged 2 to 17, although it may be continued in patients 18 years old or older, by the EMA.