Pediatric Orphan Indications
PCDH19 pediatric epilepsy is a serious and rare epileptic syndrome characterized by highly variable early-onset cluster seizures with comorbid cognitive and behavioral disturbances with or without intellectual disability. PCDH19 pediatric epilepsy is caused by a mutation in the PCDH19 gene. There is indirect evidence linking progesterone and allopregnanolone to the onset and offset of seizures in girls with PCDH19 pediatric epilepsy. Currently, there are no FDA approved therapies for this condition.
PCDH19 Pediatric Epilepsy
Clinical Development of Ganaxolone in PCDH19 Pediatric Epilepsy
We recently enrolled 11 females with PCDH19 epilepsy in a Phase 2 exploratory study to evaluate the safety and efficacy of ganaxolone in reducing seizure frequency from baseline. In this severe patient population, ganaxolone reduced seizure frequency from baseline in the majority of patients and was generally safe and well tolerated. The study has been expanded and is currently enrolling patients with CDKL5 disorder (CDKL5) and Lennox-Gastaut Syndrome (LGS), two additional pediatric orphan genetic epilepsies with difficult-to-treat seizures. More information about the trial can be found on www.clinicaltrials.gov, using Identifier NCT02358538.
Fragile X Syndrome
Photo Credit: Peter Saxon (CC BY-SA)
Fragile X Syndrome (FXS) is a genetic condition, caused by a mutation in the fmr1 gene, and is characterized by the development of a range of developmental problems, including cognitive impairment, learning disabilities and behavioral challenges. Ganaxolone and other agents that have been shown to improve GABA function have also been shown to improve FXS symptoms in a mouse model. Ganaxolone may increase signaling at existing receptors to normalize GABA function, thereby reducing anxiety, hyperactivity and other disabilities associated with this inherited disorder.
Clinical Development of Ganaxolone in FXS
Ganaxolone was evaluated for the treatment of anxiety and attention in children with FXS in a Phase 2 exploratory clinical trial. Consistent with our expectations and ganaxolone’s mechanism of action, treatment with ganaxolone improved anxiety and hyperactivity across multiple measures in FXS patients with high baseline anxiety. In addition ganaxolone was generally safe and well tolerated. The results from this study support the anxiolytic effect of ganaxolone and provide a strong rationale to advance the clinical development of ganaxolone in anxious FXS patients. Additional information about the trial is available on www.clinicaltrials.gov, using Identifier NCT01725152.