Focal Epilepsy Cell Therapy NRTX-1001 Gets IND Clearance, Set to Begin Phase 1/2 Trial


NRTX-1001 will be first evaluated in an open-label dose-escalation study, followed by a randomized blinded portion, with both featuring patients with drug-resistant mesial temporal epilepsy.

Cory Nicholas, PhD

Cory Nicholas, PhD

NRTX-1001 (Neurona Therapeutics), an inhibitory nerve cell therapy derived from human pluripotent stem cells, has received an investigational new drug (IND) clearance by the FDA, and may now proceed with its first-in-human phase 1/2 clinical trial in patients with drug-resistant mesial temporal lobe epilepsy (MTLE).

This multicenter trial will evaluate the safety, tolerability, and efficacy of single-administration NRTX-1001 in 2 stages. The first is an open-label dose-escalation study with up to 10 participants with MTLE included, while the second stage is a randomized, blinded investigation comparing the safety and efficacy of the cell therapy to a control group in a cohort of 30 people with MTLE. Delivered as a 1-time dose, NRTX-1001 is designed to secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), providing long-term GABAergic inhibition to repair hyperexcitable neural networks that underlie epilepsy and other central nervous system disorders. For now, Neurona indicated that it is intended on focusing NRTX-1001 as a restorative treatment for MTLE.

"The clearance of our first IND is a key milestone for Neurona and a testament to the talent, experience, and hard work of the entire Neurona team," Cory Nicholas, PhD, president and chief executive officer, Neurona, said in a statement. "This milestone is especially rewarding and timely given that November is Epilepsy Awareness Month. Epilepsy is one of the most common neurological disorders, affecting over 3 million people in the US, of whom approximately one-third have drug-resistant disease. NRTX-1001 is a new type of inhibitory cell therapy that is targeted to the focal seizure onset region in the brain and, in a single treatment, has the potential to significantly improve the lives of people living with focal epilepsy.”1

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The only data on NRTX-1001 has come from preclinical models, in which treatment with the cell therapy resulted in seizure-freedom for more than two-thirds of the population compared to 5% of the control group. Additionally, investigators observed signs of reduced mesiotemporal sclerosis, or tissue damage in the affected seizure-onset area of the brain, with treatment from NRTX-1001.

"To our knowledge, NRTX-1001 is the first human cell therapy candidate to enter clinical trials for epilepsy," David Blum, MD, head, Clinical Development, Neurona Therapeutics, said in a statement. "Unlike many other interventions for drug-resistant focal epilepsy, including surgical removal or ablation of brain tissue, NRTX-1001 has the potential to achieve seizure freedom in a non-tissue destructive manner.”1

Most recently, the company presented preclinical data at Neuroscience 2021, the 50th Annual Meeting of the Society for Neuroscience, November 8-11. In an intrahippocampal kainite epilepsy mode, investigators were able to establish a baseline progression of hippocampal damage that is important to the characterization of NRTX-1001. Furthermore, in the same model, treatment with NRTX-1001 was found to be well-tolerated and maintained efficient interneuron cell engraftment and disease-modifying activity when combined with antiseizure medications levetiracetam (Keppra; UCB Pharma) and diazepam (Libervant; Aquestive Therapeutics).2

The final abstract showed that NRTX-1001 transplantation into the hippocampus stably suppressed focal seizures, and significantly reduced hippocampal pathology in the mouse model of MTLE over a 7-month period. No unwanted behavioral effects were observed as a result of treatment. Additionally, the interneuron cells from NRTX-1001 persisted and distributed in the hippocampus throughout the course of the study and were not proliferative.

1. Neurona Therapeutics receives IND clearance to initiate phase 1/2 clinical trial of neural cell therapy NRTX-1001 in chronic focal epilepsy patients. News release. Neurona Therapeutics. November 4, 2021. Accessed November 8, 2021.
2. Neurona Therapeutics presents preclinical data from lead cell therapy candidate NRTX-1001 at Neuroscience 2021. News release. Neurona Therapeutics. November 8, 2021. Accessed November 8, 2021.
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