PCDH19-Related Epilepsy

At Marinus, we understand there are complex difficulties for children and their families living with PCDH19-related epilepsy.
we embrace the challenges of rare diseases and fight for our patients.

What is PCDH19-Related Epilepsy?

PCDH19-related epilepsy, which is caused by a mutation in the PCDH19 gene, is a serious and rare epileptic syndrome characterized by highly variable early-onset seizures, cognitive and sensory impairment, and psychiatric and behavioral disturbances. Seizures occur in clusters lasting from several hours to days. It is estimated that about 70% of PCDH19-related epilepsy patients have intellectual disabilities of varying degrees, ranging from mild to severe. There is indirect evidence linking progesterone and allopregnanolone to the onset and offset of seizures in girls with PCDH19-related epilepsy.

PCDH19-related epilepsy treatment options

PCDH19-related 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. Genetic testing is available to determine if a patient has a PCDH19 mutation. Currently, there are no drugs approved specifically for the general treatment of various seizures associated with PCDH19-related epilepsy.

The science behind treating PCDH19-related epilepsy

It has been reported that patients with PCDH19-related epilepsy have an endogenous neurosteroid deficiency, particularly allopregnanolone. Ganaxolone is a synthetic analog of allopregnanolone with similar mechanistic action as a positive allosteric modulator of GABAA receptors. Augmenting with ganaxolone may act to restore the effect of increased neurosteroid levels.

It is estimated that PCDH19-related epilepsy affects approximately 10,000-12,000, predominantly female, children in the U.S.

The clinical development of ganaxolone in PCDH19-related epilepsy

Marinus is conducting a Phase 2 proof-of-concept study, the Violet study, which is evaluating allopregnanolone sulfate as a potential predictive biomarker in the patients with a confirmed PCDH19 mutation. The Violet Study will stratify approximately 20 patients into one of two biomarker groups based on baseline allopregnanolone sulfate levels and randomize patients to ganaxolone or placebo within each stratum. The trial consists of a 12-week prospective baseline period to collect seizure data, followed by a 17-week double-blind treatment phase. Patients randomized to ganaxolone will titrate over four weeks to a dose of up to 600 mg of ganaxolone in an oral liquid suspension three times per day and maintain that dose for the following 13-weeks.

Young Girl Teddy Bear

Learn more about PCDH19-related epilepsy

Additional educational and support resources:

The Violet Study

PCDH19 Alliance

Rare Epilepsy Network

Boston Children’s Hospital

Epilepsy Foundation

PCDH19 France

Together for the Research on PCDH19 Non-Profit Organization

Links to third party sites are provided for convenience purposes only. The information contained on these sites is not information provided, controlled or monitored by Marinus Pharmaceuticals in any way. Marinus Pharmaceuticals is not responsible in any way for the accuracy, completeness, or fitness for any particular purpose of any content appearing on such sites.

Walters Family Pcdh19

Patient Story:

PCDH19-Related Epilepsy: Walters Family