Neurona Therapeutics Presents Positive Clinical Update From Cell Therapy Trial in Adults With Drug-Resistant Focal Epilepsy

Neurona Therapeutics presented updated preliminary data from its ongoing open-label Phase 1/2 clinical trial of NRTX-1001 in adults with drug-resistant, unilateral mesial temporal lobe epilepsy (MTLE) at the American Academy of Neurology (AAN) 2024 Annual Meeting in Denver, CO.

In the first cohort of five subjects who received the lower dose of NRTX-1001, the data demonstrate a median seizure reduction from baseline of 75%, with four of five subjects reporting >50% seizure reduction from baseline, in the 6 months after treatment. Two subjects have been followed for 16- and 21-months after administration of NRTX-1001 and report durable, >95% seizure reduction from baseline and increased quality-of-life test scores.  NRTX-1001 has been well-tolerated to date in all treated subjects, and neuropsychological testing suggests the absence of detectable neurocognitive impairment.

“The emerging data demonstrate that administration of NRTX-1001 is well-tolerated and has the potential to significantly reduce seizure frequency,” said John Hixson, MD, Senior Medical Director at Neurona. “We are very encouraged by the data from these first subjects, who continue to exhibit durable seizure suppression for up to 21 months post-administration. Unlike lobectomy surgery, which poses serious cognitive risks due to brain tissue destruction, NRTX-1001 potentially represents a regenerative cell therapy approach aimed at restoring balanced neural activity without compromising cognitive function. Notably, the first five subjects have not demonstrated deficits from baseline on neuropsychological or quality-of-life tests, and some test scores have increased from baseline, after NRTX-1001 administration.”

The five subjects in the first cohort of the ongoing clinical trial (NCT05135091) each received a one-time administration of NRTX-1001, which is an allogeneic, off-the-shelf, cell therapy that does not require immunological matching or preconditioning. To promote the long-term persistence of NRTX-1001, temporary oral immunosuppression was administered during the first year. All subjects entered the study with a history of significant seizure activity that was not controlled by at least two anti-seizure medications. Baseline monthly seizure frequency was established by reviewing subjects’ medical history from the six months prior to the administration of NRTX-1001.

The first two subjects have been followed for 21- and 16-months after NRTX-1001 administration, respectively. The first subject, with a seven-year history of drug-resistant seizures averaging 32 per month at baseline, has reported 96% seizure reduction and freedom from focal impaired awareness seizures (their most severe seizure type) since the first month after NRTX-1001 administration. The second subject, with a nine-year history of seizures averaging 14 per month at baseline, reported >97% seizure reduction since treatment and seizure-freedom since the seventh month after NRTX-1001 administration. The reduction in seizure frequency has been maintained in the nine and four months after the tapering and discontinuation of the immunosuppression regimen in Subject 1 and Subject 2, respectively.

The remaining three subjects in the first cohort have been followed for six months post-treatment. Subject 3, with a 16-year history of drug-resistant seizures averaging 26 per month at baseline, reported 74% seizure reduction and freedom from their most disabling focal seizure type since administration of NRTX-1001. Subject 4, with a 6-year history of epilepsy averaging two seizures per month at baseline, reported fluctuation in seizure frequency during the first three months post-treatment and subsequently had 33% seizure reduction from baseline in months 4-6 after NRTX-1001 administration. Subject 5, with a three-year history of epilepsy averaging 40 seizures per month at baseline, experienced a 75% seizure reduction since treatment.

Comprehensive neurocognitive tests that measure verbal and spatial memory demonstrated an absence of detectable neurocognitive impairment from baseline in the first cohort to receive NRTX-1001, with some subjects exhibiting improved verbal and/or spatial memory and quality-of-life test scores.

NRTX-1001 has been well-tolerated in all subjects to date. One subject in the first cohort had two serious adverse events in the third month after NRTX-1001 administration consisting of a cluster of seizures (status epilepticus) and seizure cluster-induced kidney injury deemed to be related to medical history and not related to cell treatment, delivery procedure, or immunosuppression. This subject had a prior history of similar episodes and has not had further episodes to date. All other adverse events have been non-serious, mild to moderate in severity, and attributed to either the delivery procedure or to the immunosuppression regimen. Procedural-related adverse events resolved within the first month post-administration, while immunosuppression-related adverse events resolved in the first subjects who discontinued immunosuppression per protocol in the second year.

The first two subjects in the second cohort of the ongoing trial have received the higher dose of NRTX-1001 and have not reported any serious adverse events to date.

Additionally, the FDA’s recent clearance of a second study to evaluate NRTX-1001 in 10 adult subjects with drug-resistant bilateral MTLE marks an important milestone. Enrollment is currently underway at epilepsy centers across the US.

The multicenter, Phase 1/2 clinical trial is designed to evaluate the safety and efficacy of a single administration of NRTX-1001 for drug-resistant MTLE. The first stage of the trial is an open-label dose-escalation study in up to 10 subjects with MTLE, with five patients to be treated at a starting dose and five at a higher dose. Patients treated with a single infusion of NRTX-1001 will be monitored for safety, tolerability, and effects on their epilepsy disease symptoms. Patient recruitment is underway at epilepsy centers across the United States. For more information, please visit www.clinicaltrials.gov (NCT05135091). The first stage of the clinical trial is supported by an $8.0 million grant from the California Institute for Regenerative Medicine (CIRM; CLIN2-13355).

NRTX-1001 is a regenerative cell therapy candidate derived from human pluripotent stem cells. The fully-differentiated neural cells, called interneurons, secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Delivered as a one-time administration, the human interneurons are intended to integrate, persist, and provide long-term GABAergic inhibition to repair hyper-excitable neural networks.

An estimated three million Americans have epilepsy, and 25% to 35% live with ongoing seizures despite treatment with approved drugs, illustrating a significant unmet medical need in this community. MTLE is a common type of focal epilepsy in adults and primarily affects the internal structures of the temporal lobe, where seizures often begin in a structure called the hippocampus. For people with seizures that are resistant to drugs, epilepsy surgery – where the damaged temporal lobe is surgically removed or ablated by laser – can be an option. However, the current surgical options are not available or effective for all patients, are tissue-destructive, and can have significant adverse effects.

Neurona is developing allogeneic, off-the-shelf, regenerative neural cell therapy products with curative potential that are designed to provide long-term repair of the nervous system after a single administration. For more information, visit www.neuronatherapeutics.com.