On January 13, 2021, pharmaceutical company Marinus Pharmaceuticals, Inc. (“Marinus”) shared via press release that the FDA gave the company a positive response following efficacy and safety data from the Phase 3 Marigold Study. During the study, researchers evaluated orally administered ganaxolone for patients with CDKL5 deficiency disorder (“CDKL5”). Following the positive response, Marinus is now looking at filing a New Drug Application (NDA) for ganaxolone.
According to Marinus:
Ganaxolone is a GABAA receptor modulator that acts by regulating brain activity. This process can include inhibiting the abnormal electrical discharges that cause seizures and status epilepticus or restoring balance in disrupted neuronal activity in other neurologic and psychiatric disorders.
The drug can be administered intravenously and orally. So far, over 1,600 individuals have received ganaxolone. Outside of CDKL5, Marinus is also exploring the drug as a potential treatment for tuberous sclerosis complex and status epilepticus.
In September 2020, positive data was reported from the Phase 3 Marigold Study, which sought to understand the safety, efficacy, and tolerability of ganaxolone for CDKL5 in both adult and pediatric patients. Additionally, the study looked to see the possibility of dosing pediatric patients 3x each day. During the trial, ganaxolone significantly reduced the frequency of major seizures, especially in comparison to a placebo. Generally, the drug was both safe and well-tolerated, although some reported excessive sleepiness.
Marinus hopes to submit a NDA for ganaxolone before the end of 2021.
Named for the gene which causes it, CDKL5 deficiency disorder is characterized by seizures and developmental delays. Normally, CDKL5 plays a role in creating proteins that help prompt normal brain development. However, CDKL5 mutations cause protein deficiencies. Although this is a genetic disorder, it is possible to develop CDKL5 without any family history. An estimated 90% of all individuals with CDKL5 are female. Males with this disorder typically have more severe symptoms and developmental delays. Symptoms and characteristics include:
- Severe developmental delays
- Intellectual disabilities
- Treatment-Resistant seizures which begin within 3 months of birth
- Difficulties with feeding
- Teeth grinding
- Repetitive hand movements
- Constipation and other gastrointestinal issues
- Delayed standing, sitting, and walking ability
- Note: Only 1/3 of all patients with CDKL5 can walk independently.
- Limited speaking ability
- Sleep interruptions
- A high, broad forehead with large, deep-set eyes
- Widely spaced teeth
Learn more about CDKL5.