Marinus Pharmaceuticals is advancing its development program for ZTALMY® (ganaxolone) in tuberous sclerosis complex (TSC), with topline data from the Phase 3 TrustTSC trial expected in the fourth quarter of 2024. The company plans to submit a supplemental New Drug Application (NDA) to the FDA in April 2025, seeking priority review. These milestones could potentially offer a new treatment option for patients with TSC, many of whom experience refractory seizures.
TrustTSC Trial Progress
The global Phase 3 TrustTSC trial, which completed enrollment in May 2024, is designed to detect a 25% difference from placebo in percent seizure reduction with 90% power. Notably, the trial maintained a low discontinuation rate of 6.2%, and approximately 93% of patients continued into the open-label extension, suggesting good tolerability and potential efficacy. This is particularly important, as Scott Braunstein, M.D., Chairman and Chief Executive Officer of Marinus, noted, it increases confidence that ZTALMY has the potential to be a meaningful treatment option for TSC patients with refractory epilepsy.
Long-Term Efficacy Data
Long-term extension data from a Phase 2 TSC trial demonstrated durable and increasing reductions in seizure frequency among patients treated with ganaxolone over two years. Patients experienced a cumulative median reduction in seizure frequency of 56% within two years (n=9). Furthermore, a subset of patients (n=6 with available data) experienced a median reduction in seizure frequency of 87% during months 22-24. These findings suggest the potential for sustained, long-term efficacy of ganaxolone in TSC patients.
Commercial and Financial Outlook
Marinus Pharmaceuticals is on track to achieve full-year 2024 ZTALMY net product revenue guidance of between $33 and $35 million. The company also anticipates a new patent allowance from the USPTO for ganaxolone oral titration regimens, expected to run through September 2042, which could bolster its market position. However, the company's cash and cash equivalents of $64.7 million as of June 30, 2024, are expected to fund operations only into the second quarter of 2025, necessitating potential additional funding before a possible TSC launch.
Unmet Needs in TSC Treatment
Market research indicates a significant unmet need among TSC patients with refractory epilepsy. Real-world claims data show that approximately 26% of TSC patients have tried and failed three or more antiseizure medications. This underscores the potential market opportunity for ZTALMY, if approved for this indication. According to Dr. Mary Kay Koenig, M.D., Director of the Center for Treatment of Pediatric Neurodegenerative Disease (CTPND), there remains a substantial unmet need for therapies that can reduce the frequency of seizures in children and adults with TSC.
Expansion into Other Epilepsies
Marinus is also planning to expand ZTALMY development into other developmental and epileptic encephalopathies, including Lennox-Gastaut syndrome, with clinical trials potentially beginning in the second half of 2025, pending the TSC topline data. Additionally, the company is targeting submission of an Investigational New Drug application for a novel oral ganaxolone prodrug in the fourth quarter of 2025, further broadening its pipeline.
