Epilepsy, Temporal Lobe

Interim data presented by the company last July demonstrated a dose-dependent slowing of the progression of Huntington’s Disease in individuals treated with the therapy. Credit: bangoland/Shutterstock. The US Food and Drug Administration (FDA) has awarded breakthrough therapy designation to uniQure’s AMT-130 for treating Huntington’s disease, a rare neurodegenerative condition. This designation for the therapy adds to a list of the agency’s recognitions, including regenerative medicine advanced therapy (RMAT), fast track and orphan drug designations. Clinical data from the ongoing Phase I/II studies of the therapy support this latest designation. Interim data presented by the company last July demonstrated a dose-dependent slowing of progression of the disease in individuals treated with the therapy, against a propensity-weighted natural history. Till now, 45 subjects received the treatment. uniQure chief medical officer Walid Abi-Saab said: “Receiving breakthrough therapy designation underscores both the urgent need for effective treatments for Huntington’s disease and the encouraging interim data demonstrating that AMT-130 has the potential to slow disease progression. “It’s a powerful recognition of the promise of AMT-130 and the important progress we’ve made. We deeply value the FDA’s continued commitment to advancing innovative gene therapies for patients with critical unmet needs, and we look forward to working closely with the agency to bring AMT-130 to the Huntington’s disease patient community as quickly as possible.” The breakthrough therapy status is granted to accelerate investigational therapies development for serious conditions when preliminary clinical evidence suggests a substantial improvement over existing treatments. uniQure noted that Huntington’s disease, which results in chorea, cognitive decline, and behavioural abnormalities, affects approximately 70,000 people in Europe and the US, with many more at risk. The company’s gene therapy for haemophilia B has paved the way for new treatment approaches in genomic medicine. uniQure is currently progressing with its pipeline of gene therapies aimed at treating Huntington’s disease, refractory temporal lobe epilepsy, Fabry disease, amyotrophic lateral sclerosis (ALS), and other severe conditions.

–EFFICACY: 92% median reduction in disabling seizures during 7-12-month efficacy endpoint period, and 80% (4/5) of patients responding with >75% seizure reduction in Cohort 1. –DURABILITY: All responders (4/4) in Cohort 1 continue to have durable seizure control for 18-24 months after a single-dose of NRTX-1001. –COGNITION AND QUALITY OF LIFE: All patients (5/5) in Cohort 1 had significantly improved quality-of-life test scores, with no patient experiencing persistent decline in cognition. – SAFETY: NRTX-1001 continues to be well-tolerated at both high and low doses with no adverse events attributed to the cell therapy. –NEXT STEPS: Phase 3 EPIC trial planned to start enrolling in 2H 2025, as aligned with FDA under RMAT designation, to support submission of a Biologics License Application (BLA). April 08, 2025 -- Neurona Therapeutics, a clinical-stage biotherapeutics company developing regenerative cell therapies for epilepsy and other disorders of the nervous system, today presented updated data from its 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) 2025 Annual Meeting in San Diego, CA. The ongoing multicenter Phase 1/2 trial for unilateral MTLE has enrolled 18 subjects in Cohorts 1 and 2 across 13 comprehensive epilepsy centers in the United States, and 10 subjects have been followed for 9 to 24 months after NRTX-1001 administration. Patients in the low-dose Cohort 1 (N=5) achieved median disabling seizure reduction of 92% from baseline during the primary efficacy evaluation period in months 7-12 post-treatment, and a 97% median reduction of disabling seizures after month 13. In the high dose Cohort 2 (N=5), patients achieved median disabling seizure reduction of 72% from baseline in months 4-9, the most recent 6-month epoch, and have not yet reached month 12. “We are pleased with the results to-date from the ongoing trial of NRTX-1001 cell therapy,” said Dr. Jerry Shih, M.D., Neurologist and Director of the University of California San Diego (UCSD) Comprehensive Epilepsy Center, who has treated 4 subjects in the trial alongside UCSD Neurosurgeon and Surgical Director of Epilepsy, Dr. Sharona Ben-Haim, M.D. “Our first subject in the study is now 19 months post-cell administration and has experienced a 98% reduction in his drug-resistant disabling seizures. He successfully stopped the temporary immunosuppression regimen 6 months ago, and continues to have a durable outcome, free from any study-related adverse effects. If these results continue to be observed in the upcoming Phase 3 EPIC trial, cell therapy has the potential to become a paradigm-shifting treatment option for patients with drug-refractory focal epilepsy.” Said Dr. John Hixson, M.D., VP of Clinical Development at Neurona, “The results of the trial thus far point to the promise of NRTX-1001 being a cell therapy that can address a major unmet need for patients with drug-resistant focal seizures, providing durable seizure control and avoiding the significant risk of permanent neurocognitive impairment from current tissue-destructive surgeries like laser ablation and brain resection. To that end, NRTX-1001 could represent a new treatment option that preserves brain tissue and function.” Dr. Hixson continued, “We are pleased with the continued durability signal from the ongoing NRTX-1001 study, supporting a single ‘one-and-done’ dose. We are also very encouraged by the lack of cell-related adverse effects and absence of neurocognitive impairment thus far. In summary, the data give us confidence to proceed with our planned Phase 3 EPIC trial of NRTX-1001, as we seek to bring this novel therapy to patients as safely and expeditiously as possible.” Results: Low Dose Effect on Disabling Seizures (N=5): Months 7-12: 92% median seizure reduction Months 13+: 97% median seizure reduction Durability: All (4/4) patients who exhibited marked seizure reduction in first year continue to have durable seizure control in second year after completing the 12-month immunosuppression regimen, which is intended to facilitate long-term persistence of the allogeneic cell therapy Quality-of-Life: All patients have significantly improved Quality-Of-Life In Epilepsy (QOLIE) overall test scores from baseline levels High Dose Effect on Disabling Seizures (N=5): Months 4-9 (latest 6-month epoch to date): 72% median seizure reduction 80% (4/5) subjects with >50% seizure reduction from baseline Safety – Low and High Dose Cohorts (N=10): No adverse events determined to be related to NRTX-1001 Neurocognition – Low and High Dose Cohorts (N=10): No persistent decline in cognition based on word retrieval, verbal memory, and visuospatial memory batteries The open-label Phase 1/2 clinical trial was designed to evaluate the safety and preliminary efficacy of a single-dose administration of NRTX-1001 inhibitory neuron cell therapy for drug-resistant unilateral MTLE. This ongoing trial has been expanded to include 8 additional subjects for a total of 18 subjects across both cohorts: low-dose cohort 1 (N=9) and high-dose cohort 2 (N=9). Study subjects are being monitored for safety, tolerability, and effects on their epilepsy disease symptoms. In addition, a second multicenter, open-label Phase 1/2 clinical trial has been initiated to evaluate NRTX-1001 in adults with drug-resistant bilateral MTLE. For more information, please visit www.clinicaltrials.gov (NCT05135091 and NCT06422923). In February, the company announced plans to initiate its Phase 3 EPIC (EPIlepsy Cell therapy) trial, which is expected to be a single pivotal study and primary basis of a future BLA submission for NRTX-1001 in drug-resistant MTLE, based on alignment gained with FDA under the RMAT designation. The EPIC trial is anticipated to begin in the second half of 2025 and is designed as a randomized, sham-controlled, double-blind study of NRTX-1001 in adults with drug-resistant MTLE, the most common type of epilepsy in adults. Earlier this month, Neurona closed an upsized and oversubscribed $102 million private financing with support from new and existing investors. AAN Presentation Details: Title: First-in-Human Trial of NRTX-1001 GABAergic Interneuron Cell Therapy for Focal Epilepsy - Updated Clinical Trial Results Presenting Author: John D. Hixson, M.D., VP of Clinical Development, Neurona Presentation: Tuesday April 8, 2025; Poster Session 8 (8:00 AM-9:00 AM); Number: 9-003 Neurona is developing allogeneic, off-the-shelf, regenerative neural cell therapies with the potential to provide long-term targeted repair of the nervous system following a single administration. The Company’s lead product candidate, NRTX-1001, comprising GABAergic interneurons, is currently being studied for safety and efficacy in two ongoing open label multicenter Phase 1/2 trials: NCT05135091 for drug-resistant unilateral mesial temporal lobe epilepsy (MTLE), and NCT06422923 for drug-resistant bilateral MTLE, with expansion to neocortical focal epilepsy and other indications planned in the future. The Phase 1/2 MTLE clinical trials are supported by grants from the California Institute for Regenerative Medicine (CIRM; CLIN2-13355 and CLIN2-17135). The FDA granted the Regenerative Medicine Advanced Therapy (RMAT) designation to NRTX-1001 in June 2024. The content above comes from the network. if any infringement, please contact us to modify.

Mesial temporal lobe epilepsy is the most common form of epilepsy. Credit: PonyWang via Getty Images. Neurona Therapeutics has gained $102m to support the advancement of its investigational cell therapy, NRTX-1001, into Phase III testing for drug-resistant mesial temporal lobe epilepsy (MTLE). The financing – secured after Neurona’s $120m fundraising round in February 2024 – will also help expand the company’s pipeline of allogeneic cell therapy candidates for chronic neurological disorders. Investors in the latest round include Fidelity Management & Research Company, The Column Group, Soleus Capital, Viking Global Investors, and Cormorant Asset Management. NRTX-1001 is a regenerative stem cell therapy designed to deliver neural cells that secrete the neurotransmitter gamma-aminobutyric acid (GABA), silencing seizure activity in the epileptic region of the brain. NRTX-1001 is derived from human pluripotent stem cells, which are manufactured in-house by Neurona. The company aims to position it as a potential alternative to brain surgery, which remains the standard intervention for drug-resistant MTLE but carries risks of memory impairment and other neurocognitive deficits. Neurona has stated that NRTX-1001, administered as a one-time treatment, could provide a durable reduction in seizure frequency while preserving brain function. The Phase III EPIC trial is expected to begin enrolling patients in H2 2025 following what Neurona described as “productive discussions” with the US Food and Drug Administration (FDA). The agency granted NRTX-1001 a regenerative medicine advanced therapy (RMAT) designation in June 2024. The trial will enrol adults with drug-resistant MTLE in a randomised, double-blind design, assigning patients to either NRTX-1001 or a sham-control group in a 2:1 ratio. Patients in the control arm will have the option to receive the therapy once the primary endpoint is reached. Early-stage clinical data suggest the therapy could offer meaningful benefits. In an ongoing Phase I/II trial (NCT05135091), NRTX-1001 has been well tolerated, and interim results presented at the American Epilepsy Society annual meeting in December 2024 showed that two patients who received a low-dose treatment reported a more than 97% reduction in seizures two years after administration. There is a growing drive for innovative treatments as up to one-third of the estimated 50 million people with epilepsy do not respond to existing therapies. While current therapies include surgery, neurostimulation devices, and dietary interventions, there is increasing interest in regenerative and precision medicine approaches. Neurona is also exploring the potential of NRTX-1001 for other neurological conditions, including Alzheimer’s disease, where it is currently in preclinical evaluation.