Marinus Pharmaceuticals' Ganaxolone Fails Phase 3 Trial for Tuberous Sclerosis Complex
核心洞察
Marinus Pharmaceuticals' Phase 3 TrustTSC trial of oral ganaxolone for tuberous sclerosis complex (搜索) (TSC)-associated seizures did not meet its primary endpoint.
Ganaxolone showed a 19.7% median reduction in seizure frequency compared to 10.2% for placebo, but the results were not statistically significant (p=0.09).
Marinus will discontinue further ganaxolone development, reduce costs, and explore strategic alternatives, while continuing to support ZTALMY for CDKL5 deficiency disorder (搜索).
Marinus Pharmaceuticals' Phase 3 TrustTSC trial evaluating oral ganaxolone for the treatment of seizures associated with tuberous sclerosis complex (搜索) (TSC) did not meet its primary endpoint. The trial, involving children and adults with TSC-related epilepsy (搜索), aimed to demonstrate a statistically significant reduction in seizure frequency. While ganaxolone showed a numerical improvement over placebo, the results fell short of statistical significance. This outcome has led Marinus to discontinue further development of ganaxolone and explore strategic alternatives.
The TrustTSC trial was a global, randomized, double-blind, placebo-controlled study involving 129 participants. Patients were administered adjunctive oral ganaxolone. The primary endpoint was the percent change in 28-day TSC-associated seizure frequency. While the ganaxolone arm showed a 19.7% median reduction in seizure frequency compared to a 10.2% reduction in the placebo arm, the difference did not reach statistical significance (p=0.09).
Safety and Tolerability
Ganaxolone was generally well-tolerated in the TrustTSC trial, with a safety profile consistent with previous clinical trials. The most frequent adverse event reported was somnolence, occurring in 28.1% of patients on ganaxolone compared to 16.9% on placebo.
Strategic Shift for Marinus
Following the unsuccessful trial results, Marinus Pharmaceuticals is implementing significant changes. The company will discontinue further clinical development of ganaxolone and reduce costs through workforce reductions. Marinus has engaged Barclays as an advisor to explore strategic alternatives, suggesting a potential sale or restructuring of the company.
Scott Braunstein, M.D., Chairman and Chief Executive Officer of Marinus, stated, "We are disappointed that the results of the TrustTSC trial are not likely to be sufficient for an sNDA filing." He also acknowledged the contributions of the clinical trial investigators, patients, and caregivers.
Focus on ZTALMY
Marinus will continue to support ZTALMY (ganaxolone) oral suspension CV, which is FDA-approved for the treatment of seizures associated with CDKL5 deficiency disorder (搜索) in patients two years of age and older. Currently, over 200 patients are receiving treatment with ZTALMY.
Tuberous Sclerosis Complex (TSC)
Tuberous sclerosis complex (搜索) (TSC) is a rare genetic disorder characterized by the growth of non-cancerous tumors in various organs, including the brain, skin, kidneys, heart, and lungs. Neurological manifestations, such as refractory seizures and neurodevelopmental delays, are common. Epilepsy (搜索) is observed in up to 90% of TSC patients.
The TrustTSC trial (NCT05323734) enrolled participants at sites in the U.S., Western Europe, Canada, Israel, Australia, and China. Eligible participants had inadequate seizure control despite treatment with at least two prior antiseizure medications. The trial consisted of a four-week baseline period, followed by a 16-week double-blind treatment phase.