Marinus Pharmaceuticals has announced that its Phase III TrustTSC trial of oral ganaxolone for the treatment of seizures associated with tuberous sclerosis complex (TSC) did not meet its primary endpoint. The global, randomized, double-blind, placebo-controlled study involved 129 participants but failed to demonstrate a statistically significant reduction in seizure frequency compared to placebo.
TrustTSC Trial Details
The TrustTSC trial aimed to assess the efficacy and safety of ganaxolone in individuals with TSC experiencing seizures. Participants were administered oral ganaxolone, and the primary endpoint was the change in 28-day seizure frequency. Topline data indicated a median reduction in seizure frequency of 19.7% with ganaxolone compared to placebo. However, this reduction did not reach statistical significance, leading to the trial's failure to meet its primary objective.
Impact on Ganaxolone Development
Following the unsuccessful trial results, Marinus Pharmaceuticals is discontinuing further clinical development of ganaxolone for TSC. The company is also implementing cost-reduction measures, including a reduction in workforce. Despite this setback, Marinus will continue to support the commercial growth of ganaxolone oral suspension CV (ZTALMY), which is already approved by the U.S. Food and Drug Administration (FDA) for seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder in patients aged two years and older.
Management's Perspective
Scott Braunstein, chairman and CEO of Marinus, acknowledged the disappointing outcome but highlighted the study's contribution to understanding ganaxolone's use with other standard-of-care treatments. "As the first controlled trial in TSC that allowed enrollment of patients taking a range of concomitant antiseizure medications, which included mTOR inhibitors and cannabidiol, these data represent a significant advancement in our understanding of the use of ganaxolone with other standard of care treatments," Braunstein stated. He also expressed gratitude to the investigators, patients, and caregivers who participated in the study.
Strategic Alternatives
Marinus Pharmaceuticals has initiated a process to explore strategic alternatives to enhance shareholder value and has appointed Barclays to assist in this review. The company aims to identify opportunities that will maximize the potential of its existing assets and pipeline.
Ganaxolone's Existing Approval
Ganaxolone, a neuroactive steroid gamma-aminobutyric acid (GABA)A receptor modulator, received FDA approval in March 2022 for treating seizures associated with CDKL5 deficiency disorder. This approval marked a significant milestone for patients with this rare and severe form of epilepsy. The drug acts on a target in the brain with anti-seizure effects.
Recent RAISE Trial Results
Earlier this month, Marinus reported results from the pivotal Phase III RAISE trial for intravenous (IV) ganaxolone in treating refractory status epilepticus (RSE).
