An independent DSMB has also recommended continued enrollment in the trial’s first cohort.
The FDA has cleared an amendment for the ongoing phase 1/2 clinical trial (NCT05135091) for Neurona Therapeutics’ NRTX-1001, an allogeneic regenerative neural cell therapy intended to treat drug-resistant mesial temporal lobe epilepsy (MTLE), expanding the enrollment criteria to include both patients with dominant-lobe disease and patients with non-dominant lobe disease.1
NRTX-1001 is comprised of interneurons derived from human pluripotent stem cells that provide long-term secretion of gamma-aminobutyric acid (GABA). The cells are intended to replace damaged neurons and repair neural networks through long-term GABAergic inhibition. In addition to the news of the expanded inclusion criteria, Neurona Therapeutics also announced that an independent Data and Safety Monitoring Board (DSMB) recommended continued enrollment in the trial’s first cohort, which has treated 2 patients with drug-resistant seizures so far, based on a prespecified data review.
The company noted that the first patient treated, whose dosing was announced in June of last year, had a history of seizures over 9 years, with an average of 32 seizures per month reported in the 6 months prior to treatment with NRTX-1001.1,2 Meanwhile, the second patient treated had an average of 14 seizures per month in the 6 months preceding NRTX-1001 administration. The first patient achieved over a 90% reduction in seizure counts within 6 months of administration and the second patient achieved over a 90% reduction within 3 months of administration. In terms of safety, NRTX-1001 was well-tolerated, and no serious or severe adverse events (AEs) were reported in the treated patients. The company additionally reported at the annual meeting of the American Epilepsy Society, held in Nashville, Tennessee, December 2-6, 2022, that the first patient had 4 seizures in the first 3 months following treatment, and the second patient had 1 seizure in the first month after treatment.3
“We are delighted with the FDA’s decision, which enables enrollment of patients with focal epilepsy that originates in either the dominant or the non-dominant hemisphere and will effectively double the eligible patient population,” Cory R. Nicholas, PhD, chief executive officer, Neurona Therapeutics, said in a statement regarding the news.1 “In addition, with the DSMB’s clearance to continue the study, we are working with major epilepsy centers across the US to enroll the remaining patients into the first cohort of the NRTX-1001 trial. We remain cautiously optimistic that the early signs of safety and potential efficacy will continue for our existing and future patients. With additional data from the full cohort, we will determine how to most efficiently advance this novel regenerative cell therapy with the potential to transform the lives of patients for whom anti-seizure medication has failed.”
The multicenter trial’s first stage, which is an open-label dose-escalation, is anticipated to recruit up to 10 patients in total, with half to be treated at a lower dose and half to be treated at a higher dose. The second stage will enroll up to 20 participants in an experimental arm and up to 10 participants in a sham comparator arm. The trial's primary end point is the frequency of serious or severe AEs in a 1-year post-administration period and will compare participants from both stages who received NRTX-1001 to those who received the sham treatment. The trial's secondary end points are the change in seizure frequency and the difference in the 75% responder rate between participants who receive NRTX-1001 in stage 2 and those who receive the sham treatment. The California Institute for Regenerative Medicine has provided $8 million in funding which will be used to support the trial’s first stage.
“When MTLE originates in the verbal-memory dominant hemisphere, typically the left hemisphere in right-handed individuals, there are risks with the current standard of care, lobectomy surgery, because it puts them at risk of memory impairment post-surgery,” David Blum, MD, chief medical officer, Neurona Therapeutics, added to the statement.1 “Individuals with dominant lobe disease have an even greater need for less invasive options that have the potential to be disease-modifying, like NRTX-1001, and we are encouraged that our clinical trial is now open to these individuals.”