Phase 3 EPIC Trial to Evaluate NRTX-1001 Cell Therapy in Drug-Resistant Mesial Temporal Lobe Epilepsy

Details of the phase 3 EPIC trial evaluating NRTX-1001 (Neurona), an investigational GABAergic interneuron cell therapy, highlight a potential tissue-sparing approach to reducing seizure frequency in adults with drug-resistant mesial temporal lobe epilepsy (MTLE), according to an abstract from the 2026 American Academy of Neurology (AAN) Annual Meeting.¹

The study, attributed to Manher Joshi, MD, chief medical officer at Neurona, and colleagues, outlines a multicenter, randomized, double-blind, sham-controlled trial designed to serve as a pivotal evaluation of the therapy. Adults with drug-resistant MTLE will undergo a 10-week baseline period before randomization (2:1) to receive a single intrahippocampal administration of NRTX-1001 or a sham procedure, with both groups receiving protocol-defined immunosuppression.

The primary end point will assess the difference between treatment arms in median percent change in seizure frequency, measured as a 28-day average, from baseline to 4 to 6 months post-treatment. Secondary and exploratory outcomes include responder rates, safety, EEG findings, neurocognitive outcomes, mood, and quality of life measures. Following the blinded portion, patients in the sham arm will be eligible to receive NRTX-1001, while treated patients will taper immunosuppression at 1 year.¹

NRTX-1001 is a first-in-class regenerative cell therapy derived from human pluripotent stem cells, designed to restore inhibitory signaling by delivering medial ganglionic eminence–like GABAergic interneurons directly into seizure foci. Unlike resective or ablative procedures, the approach aims to rebalance neural circuitry without removing brain tissue, an important consideration for patients at risk of cognitive decline with conventional surgery.²

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The phase 3 program builds on a growing body of early-phase and translational data. In an ongoing phase 1/2 study of adults with unilateral MTLE, NRTX-1001 has been well tolerated, with no treatment-related serious adverse events reported and signals of durable seizure reduction.¹ Company-reported data presented in 2025 demonstrated a median 92% reduction in disabling seizures in the low-dose cohort, with 80% of treated patients achieving greater than 80% seizure reduction during the primary evaluation period.³ Notably, among patients followed for up to 24 months, some maintained greater than 97% seizure reduction after a single administration, suggesting the potential for long-lasting benefit.³

Preclinical findings further supported the biologic rationale for this approach. In chronic MTLE mouse models, a single intrahippocampal dose of NRTX-1001 led to sustained suppression of focal seizures, with transplanted interneurons demonstrating long-term survival, functional integration, and synaptic activity within host circuits. These effects were accompanied by reduced hippocampal pathology and improved survival, without evidence of adverse behavioral effects.

Drug-resistant MTLE remains one of the most challenging epilepsy subtypes, with many patients continuing to experience frequent seizures despite antiseizure medications and facing limited options beyond invasive surgical interventions. If successful, the EPIC trial may help define whether a single-administration, cell-based therapy can provide durable seizure control while preserving cognitive function, representing a potential shift in the treatment paradigm for focal epilepsy.¹

During the 2024 American Epilepsy Society (AES) Annual Meeting, NeurologyLive^® sat down with Jonathan Parker, MD, PhD, an epilepsy expert who ran one of the phase 1/2 study sites, to discuss more about NRTX-1001. In the clip below, Parker outlined the rigorous preclinical work that has gone into ensuring these cells remain stable, do not revert to pluripotency, and avoid unintended effects like excitatory neuronal behavior. Parker, an assistant professor of neurosurgery and neuroscience at Mayo Clinic Arizona, provided an overview of how the study is conducted and expressed optimism about advances in cell therapies, particularly autologous approaches that could eliminate the need for immunosuppression.

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REFERENCES
1. Joshi MA, Banik G, Bershteyn M, et al. Phase 3 EPIC (EPIlepsy Cell Therapy) clinical trial design: NRTX-1001 GABAergic interneuron cell therapy for the treatment of drug-resistant mesial temporal lobe epilepsy. Presented at: 2026 American Academy of Neurology Annual Meeting; April 18–22, 2026; Chicago, IL.
2. Bershteyn M, Bröer S, Parekh M, et al. Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy. Cell Stem Cell. 2023;30(10):1331-1350.e11.
3. Neurona Therapeutics. Updated phase 1/2 clinical data of NRTX-1001 in drug-resistant mesial temporal lobe epilepsy. Presented at: American Epilepsy Society Annual Meeting; 2025.