In updated Phase 1/2 data for unilateral mesial temporal lobe epilepsy (MTLE), a single low dose of NRTX-1001 produced a 92% median reduction from baseline in disabling seizures during the 7–12-month efficacy window, with an 80% responder rate for patients achieving more than 75% seizure reduction at 12 months (4 of 5). All responders followed for 18–24 months (4 of 4) maintained durable seizure control. Quality-of-life scores improved in all treated subjects in Cohort 1, and no persistent cognitive decline has been observed to date. The therapy continues to be well-tolerated, with no serious adverse events attributed to the cell therapy reported.
The new development is operational rather than readout-driven: the first adult subject with drug-resistant unilateral MTLE without mesial temporal sclerosis (MTS) has been treated in an expansion cohort of Neurona Therapeutics’ ongoing Phase 1/2 trial. The non-MTS cohort is slated to enroll up to 10 adults using the same image-guided intracerebral administration as prior cohorts. In parallel, Neurona is enrolling a separate Phase 1/2 study in bilateral MTLE, has RMAT status in hand, and is preparing the Phase 3 EPIC program with initiation expected this year. The company plans to present a cross-program update at the American Epilepsy Society meeting in December, including early non-MTS and bilateral data. The combined data from unilateral and bilateral populations, with and without MTS, are intended to underpin a future BLA.
Strategically, expanding into non-MTS is a deliberate move to pressure-test the platform in a less structurally defined subtype and to build a broader label proposition. MTS provides radiographic guidance that can tighten localization and eligibility; non-MTS relies more heavily on semiology and multimodal electrophysiology and imaging, increasing heterogeneity. Demonstrating a clinically meaningful, durable reduction in disabling seizures in that setting would strengthen both the registrational narrative and the health-economic case versus tissue-destructive options. RMAT status signals regulatory openness, but the pivot from a small, open-label unilateral cohort with striking responder rates to a registrational program across phenotypes will hinge on reproducibility, effect size, and durability beyond two years.
For sites, this program concentrates activity at Level 4 epilepsy centers with neurosurgical capability, advanced EEG, MEG, PET, and intracranial monitoring. The non-MTS cohort raises the screening and adjudication burden, heightening the importance of standardized preoperative localization and consistent peri-procedural workflows, including chain-of-custody for allogeneic cell handling and stereotactic delivery. CROs will need to harmonize seizure capture and adjudication across centers, mitigate diary bias, and manage longitudinal follow-up with neurocognitive assessments. Vendors supporting neuro-navigation, imaging core labs, and data capture for seizure frequency stand to see increased demand. Regulators will scrutinize endpoint definitions, durability windows, and safety monitoring for implanted neural cells, particularly as the program moves into bilateral disease, where neurocognitive risk tolerance is lower.
The next inflection points are clarity on EPIC’s design and the breadth of the AES update. Control-arm selection, the role of baseline run-in, and whether Neurona pursues hard clinical endpoints or composite measures will set the regulatory pace. Early non-MTS and bilateral signals will indicate whether the high responder rates in MTS generalize as enrollment scales. Long-term safety, including procedure-related events and functional outcomes, remains a gating issue for a permanent cell-based intervention. Operationally, watch the pace of site activation and the geographic spread needed to meet Phase 3 timelines, alongside evidence that manufacturing can supply consistent product at scale. If the effect seen in early cohorts holds across phenotypes, the program could redefine the interventional playbook in drug-resistant focal epilepsy; if not, the field may revert to incremental advances anchored in ablative surgery and device-based neuromodulation.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
