FDA Approves Ganaxolone for Treatment CDKL5 Deficiency Disorder, a Rare Genetic Epilepsy

The Food and Drug Administration (FDA) has approved ganaxolone (Ztalmy; Marinus Pharmaceuticals, Radnor, PA) for treatment of seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency, a rare genetic epilepsy. Ganaxolone is an oral suspension and was approved for individuals, age 2 years or more. 

Children and young adults treated with ganaxolone in the phase 3 Marigold trial (NCT03572933) had a median reduction of 30.7% in seizure frequency compared with a 6.9% reduction with placebo (P=.004). Seizure frequency was measured as the occurrence of major motor seizures within a 28-day period. In the Marigold open-label extension study, patients treated with ganaxolone for at least 12 months (n=48) experienced a median 49.6% reduction in major motor seizure frequency.  

“There has been a great unmet medical need for treatments that address seizures associated with CDKL5 deficiency disorder given their prominent role and profound impact on patients,” said Scott Demarest, MD, neurologist and clinical director, Children’s Hospital Colorado. “To date, antiseizure treatment decisions have been based on very limited clinical evidence in this patient population and the resulting outcomes underscore the need for therapies that further improve seizure control. Thanks to our research and this trial, we now have the first treatment specifically approved for seizures associated with CDKL5 deficiency disorder that was shown to have a positive benefit-risk profile.” 

The most common adverse reactions (incidence of at least 5% and at least twice the rate of placebo) were somnolence, fever, salivary hypersecretion, and seasonal allergy.
Ganaxolone is a neuroactive steroid that acts as a positive allosteric modulator of the GABAA receptor.