Rationale:
GABAergic cortical interneurons from the medial ganglionic eminence (MGE) represent an important target in the development of novel therapeutics for drug-resistant epilepsy. We have developed a cortical MGE-type GABAergic interneuron allogeneic cell therapy candidate, NRTX-1001, derived from human pluripotent stem cells for single-dose administration into seizure-onset foci.
An open-label Phase 1/2 clinical trial (NCT05135091) evaluating 18 adults with unilateral MTLE with hippocampal sclerosis and refractory seizures demonstrated that NRTX-1001 is well-tolerated, with no treatment-related SAEs. Preliminary efficacy data show a significant reduction in seizure frequency and no decline in neurocognitive performance (Hixson J et al., 2025, AAN P8.003) supporting advancement into a Phase 3 registration-directed study.
Methods:
The Phase 3 EPIC (EPIlepsy Cell Therapy) trial is a multicenter, double-blind, randomized, parallel-group study, utilizing an adaptive design, enrolling adults with unilateral MTLE with hippocampal sclerosis and refractory seizures. Following a 10-week baseline seizure diary, subjects will be randomized 2:1 to receive either NRTX-1001 or a sham procedure. Subjects in the treatment arm will initiate immunosuppression prior to stereotactic, imaging-guided NRTX-1001 administration into the affected hippocampus. Immunosuppression will be tapered and discontinued after one year. Subjects randomized to sham will undergo a corresponding control procedure. Study procedures for both groups include adverse event and immune system monitoring, seizure diary collection, EEG, brain imaging, and neuropsychological tests. Each subject will be unblinded upon reaching their individual primary endpoint, and following unblinding, subjects in the sham arm will be offered NRTX-1001.
Results:
The primary efficacy endpoint will be the difference between NRTX-1001 and sham arms in the percent change from baseline in mean disabling seizure frequency, calculated as a 28-day average during months 4 to 6 after surgery. Secondary and exploratory endpoints include responder rates, median percent change from baseline in total seizure frequency, changes in anti-seizure medication use/dosage, adverse events, neurocognitive measures, mood assessments, quality of Life (QoL), and Clinical Global Impression (CGI) scales.
Conclusions:
The Phase 3 EPIC study will evaluate the safety and efficacy of NRTX-1001 GABAergic interneuron cell therapy for the treatment of drug-resistant unilateral MTLE with hippocampal sclerosis. Enrollment is expected to begin in the second half of 2025. One-time administration of NRTX-1001 regenerative cell therapy may offer the potential for substantial seizure control while preserving neurocognitive function by avoiding removal or ablation of brain tissue.
Funding:
Study sponsored by Neurona Therapeutics