The most common side effects of treatment with ganaxolone include somnolence (sleepiness), fever, excessive saliva or drooling, and seasonal allergy.[4]
The exact mechanism of action for ganaxolone is unknown; however, results from animal studies suggest that it acts by blocking seizure propagation and elevating seizure thresholds.[7][8]
Ganaxolone is thought to modulate both synaptic and extrasynaptic GABAA receptors to normalize over-excited neurons.[3] Ganaxolone's activation of the extrasynaptic receptor is an additional mechanism that provides stabilizing effects that potentially differentiates it from other drugs that increase GABA signaling.[3]
It is unknown whether ganaxolone possesses significant hormonal activity in vivo, with a 2020 study finding evidence of in vitro binding to the membrane progesterone receptor.[9]
The FDA approved ganaxolone based on evidence from a single, double-blind, randomized, placebo-controlled study (Study 1, NCT03572933) of 101 participants with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder who were two years of age and older.[4] The trial was conducted at 36 sites in 8 countries including Australia, France, Israel, Italy, Poland, Russian Federation, the United Kingdom, and the United States.[4] Forty-four (40.7%) of the participants were from US sites.[4] Safety was assessed from a pool of two clinical studies.[4] These include the study of participants with cyclin-dependent kinase-like 5 deficiency disorder and a clinical study that included seven additional participants from a trial of ganaxolone in children and young adults.[4]
^ abc"Ztalmy EPAR". European Medicines Agency. 31 July 2023. Archived from the original on 25 August 2023. Retrieved 25 August 2023.
^ abcdeCarter RB, Wood PL, Wieland S, Hawkinson JE, Belelli D, Lambert JJ, et al. (March 1997). "Characterization of the anticonvulsant properties of ganaxolone (CCD 1042; 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one), a selective, high-affinity, steroid modulator of the gamma-aminobutyric acid(A) receptor". The Journal of Pharmacology and Experimental Therapeutics. 280 (3): 1284–1295. PMID9067315.
^"PubChem compound summary for ganaxolone". PubChem databade. National Library of Medicine (National Center for Biotechnology Information). Archived from the original on 10 December 2022. Retrieved 6 August 2022.
^US20190160078A1, Masuoka, Lorianne K. & Lappalainen, Jaakko, "Ganaxolone for use in treating genetic epileptic disorders", issued 2019-05-30
Clinical trial number NCT03572933 for "Study of Adjunctive Ganaxolone Treatment in Children and Young Adults With CDKL5 Deficiency Disorder (Marigold)" at ClinicalTrials.gov