Marinus Pharmaceuticals has reported that the Phase III TrustTSC trial of oral ganaxolone in treating seizures linked to tuberous sclerosis complex (TSC) in children and adults failed to meet its primary endpoint.
ZTALMY (ganaxolone), a prescription medicine, is a neuroactive steroid gamma-aminobutyric acid (GABA)A receptor modulator and acts on a target in the brain with anti-seizure effects.
The global Phase III randomised, double-blind, placebo-controlled TrustTSC study involved 129 participants. Although the topline data indicated a median reduction in seizure frequency of 19.7% with ganaxolone compared to placebo, this difference was not statistically significant.
Ganaxolone’s safety profile remained consistent with prior clinical studies and was found to be generally well-tolerated.
The trial aimed to demonstrate a significant change in the 28-day frequency of TSC-associated seizures but fell short of achieving statistical significance.
Despite the trial’s outcome, reductions in seizure frequency were observed in the ganaxolone arm. However, the results were not sufficient to continue the clinical development of the therapy for this indication.
In response to these findings, Marinus is halting further clinical development of ganaxolone and implementing cost-reduction measures, including workforce downsizing.
Marinus chairman and CEO Scott Braunstein said: “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.
“We are disappointed that the results of the TrustTSC trial are not likely to be sufficient for an sNDA filing. We are deeply grateful for the contributions of the clinical trial investigators, patients, and caregivers whose support and participation made the study possible.”
The company has also initiated a process to explore strategic alternatives, aiming to enhance shareholder value, and has appointed Barclays to aid in this review.
Marinus will maintain its support and invest in ganaxolone oral suspension CV’s commercial growth.
The therapy received the US Food and Drug Administration (FDA)’s approval in March 2022 for seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder in patients aged two years and above.
Earlier this month, Marinus reported results from the pivotal Phase III RAISE trial for intravenous (IV) ganaxolone in treating refractory status epilepticus (RSE).
