Marinus' Ganaxolone Hits the Mark in Phase III Genetic Epilepsy Study
Shares of Marinus Pharmaceuticals soared more than 60% in after-hours trading Monday following the company’s announcement that its experimental epilepsy treatment ganaxolone hit the mark in a Phase III study.
The medication was aimed at treating children and young adults with CDKL5 deficiency disorder (CDD), a rare, genetic epilepsy with refractory seizures. Pediatric patients enrolled in the Phase III study who received ganaxolone demonstrated a 32.2% reduction of seizure burden. Patients who received a placebo only saw a 4% reduction, the company said. On average, patients enrolled had tried seven different AED medications prior to the study.
Ganaxolone is a positive allosteric modulator of GABAA receptors. Ganaxolone exhibits antiseizure, antidepressant and anti-anxiety activity via its effects on synaptic and extrasynaptic GABAA receptors.
The trial’s primary efficacy endpoint was the percentage change in 28-day frequency of major motor seizures during the double-blind phase relative to the six-week prospective baseline period. Ganaxolone was generally well tolerated with a safety profile consistent with previous clinical studies. The most frequent adverse event was somnolence, Marinus said in its announcement.
The trial showed numerical trends favoring ganaxolone across several predefined secondary endpoints, however, ganaxolone did not meet statistical significance. Ganaxolone did meet statistical significance in exploratory secondary endpoints.
Based on the results from the study, Marinus said it will submit a New Drug Application for ganaxolone as a treatment of CDD to the U.S. Food and Drug Administration in mid-2021. The company will also seek regulatory approval by the European Medicines Agency later in 2021.
Scott Braunstein, chief executive officer of Marinus, said the Phase III Marigold Study is the first double-blind and placebo-controlled study that proves efficacy specific to CDD. He said it’s also the first Phase III study to examine dosing pediatric patients three times per day with ganaxolone.
"We believe we are one step closer to providing the first treatment indicated for CDD, and plan to continue our investments in the oral ganaxolone franchise,” Braunstein said in a statement.
CDKL5 deficiency disorder is a rare genetic disorder caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, which is located on the X chromosome. CDD is characterized by early-onset, difficult-to-control seizures and severe neuro-developmental impairment. Most children affected by CDD cannot walk, talk, or feed themselves. Currently, there are no therapies approved specifically for CDD. Marinus received Rare Pediatric Disease Designation from the FDA in July.
The victory for Marinus and ganaxolone has been a long time coming. Last year, the company saw two failures within two weeks for ganaxolone trials. The drug failed to hit endpoints in an epilepsy study and also failed in a Fragile X syndrome trial. The drug also failed to hit the mark in a postpartum depression study in 2019.
“Today’s success with ganaxolone in CDD will pave the way for us to accelerate our clinical studies in tuberous sclerosis complex and possibly other rare pediatric epilepsies as well,” Chief Medical Officer Joe Hulihan said in a statement. “We will continue to explore the potential for ganaxolone’s unique mechanism of action to address other areas of unmet medical need.”