Marinus Pharmaceuticals Reports Topline Ganaxolone Phase 2 Open-Label Results in Tuberous Sclerosis Complex and Receives FDA Orphan Drug Designation

Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS), a pharmaceutical company dedicated to the development of innovative therapeutics to treat seizure disorders, today announced topline data from its open-label Phase 2 trial evaluating safety and efficacy of adjunctive oral ganaxolone treatment in 23 patients with seizures associated with tuberous sclerosis complex (TSC). The primary endpoint showed a median 16.6 percent reduction in 28-day primary endpoint seizure frequency relative to the four-week baseline period, with 30.4 percent of patients achieving a 50 percent or more seizure reduction. During the trial, patients with focal seizures (n=19) showed a median 25.2 percent reduction in focal seizure frequency.

"We believe the totality of the data is encouraging and supports advancing to Phase 3. There was notable activity in focal seizures, a meaningful 50 percent response rate, and consistent results in this refractory patient population, including patients on both cannabidiol and everolimus," said Joseph Hulihan, M.D., Chief Medical Officer of Marinus. "We look forward to initiating our Phase 3 trial and adding to the body of evidence that supports ganaxolone's potential as an innovative treatment option for rare epilepsies."

Data Highlights

• Primary endpoint showed a median 16.6 percent reduction in 28-day seizure frequency relative to baseline in TSC patients

• Secondary endpoint of 50 percent responder rate at 30.4 percent, consistent with the Marigold Phase 3 CDKL5 deficiency disorder trial of 24.5 percent

• Patients with focal seizures (n=19) showed a median 25.2 percent reduction in focal seizure frequency, the most common seizure type in TSC patients

• Proportion of patients who achieved at least a 50 percent reduction in TSC-associated seizures was 36.4 percent in patients on concomitant everolimus and 25.0 percent on patients on concomitant cannabidiol

• Ganaxolone was generally well-tolerated with somnolence reported as the most common adverse event, consistent with previous trials; in addition, one treatment-related serious adverse event of seizure was reported in the trial

The Phase 2 TSC trial, the CALM trial, was an open-label trial to evaluate the safety and tolerability of adjunctive ganaxolone treatment in patients with seizures associated with TSC. The trial enrolled 23 patients ages 2 to 32 that underwent a four-week baseline period followed by a 12-week treatment period where they received up to 600 mg of ganaxolone (oral liquid suspension) three times a day. Patients who met eligibility criteria were able to continue ganaxolone treatment during a 24-week extension to the trial. The primary endpoint for the trial was percentage change in 28-day TSC-associated seizure frequency during the 12-week treatment period relative to the four-week baseline period. Secondary outcome measures included percentage of patients experiencing a greater than or equal to 50% reduction in 28-day TSC-associated seizure frequency through the end of the 12-week treatment period compared to the 4-week baseline period.

A global Phase 3 randomized, double blind, placebo-controlled trial (TrustTSC) of adjunctive ganaxolone in approximately 160 TSC patients is expected to begin enrollment during Q4 2021. The primary endpoint is percent change in 28-day TSC-associated seizure frequency.

Regulatory Update

The FDA has granted orphan drug designation to ganaxolone for treatment in TSC. The FDA's Office of Orphan Drug Products grants orphan status to support the development of medicines for rare disorders that affect fewer than 200,000 people in the U.S. Orphan drug designation provides certain benefits, including market exclusivity upon regulatory approval, if received, exemption of FDA application fees and tax credits for qualified clinical trials.

About Tuberous Sclerosis Complex (TSC) 

Tuberous sclerosis complex (TSC) is a rare genetic disorder that affects many organs and causes non-malignant tumors in the brain, skin, kidney, heart, eyes, and lungs. The condition is caused by inherited mutations in either the TSC1 gene or the TSC2gene. TSC occurs with a frequency of 1:6,000 and a mutation is found in 85% of patients. While the disease phenotype can be extremely variable, neurologic manifestations such as epilepsy can be seen in up to 90% of TSC patients. TSC is a leading cause of genetic epilepsy, often occurring in the first year of life as either focal seizures or infantile spasms. There are currently limited approved treatments for TSC.

About Ganaxolone 

Ganaxolone, a positive allosteric modulator of GABAA receptors, is an investigational product being developed in intravenous and oral formulations intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Ganaxolone exhibits anti-seizure and anti-anxiety activity via its effects on synaptic and extrasynaptic GABAA receptors. Ganaxolone has been studied in more than 1,800 pediatric and adult subjects across various indications at therapeutically relevant dose levels and treatment regimens for up to more than two years.

About Marinus Pharmaceuticals 

Marinus Pharmaceuticals, Inc. is a pharmaceutical company dedicated to the development of innovative therapeutics to treat seizure disorders. Ganaxolone is a positive allosteric modulator of GABAA receptors that acts on a well-characterized target in the brain known to have anti-seizure, antidepressant and anti-anxiety effects. Ganaxolone is being developed in IV and oral dose formulations intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Marinus completed the first ever Phase 3 pivotal trial in children with CDKL5 deficiency disorder last year, is planning to conduct a Phase 3 trial in tuberous sclerosis complex, and a Phase 3 trial in refractory status epilepticus is ongoing. For more information visit www.marinuspharma.com.