Since its approval for the treatment of medical refractory epilepsy in 2013, the closed-loop neuromodulation device has had its efficacy and safety confirmed in several pivotal studies and will now be assessed in focal epilepsy in the RESPONSE trial.
The RESPONSE clinical trial (NCT04839601), a prospective single-arm study evaluating the safety and efficacy of NeuroPace’s Responsive Neurostimulation (RNS) System in adolescents aged 12 through 17 years with drug-resistant focal epilepsy, has commenced dosing.1
According to clinicaltrials.gov, the study is expected to enroll 200 participants who will be followed for 2 years after placement of the RNS System. The primary outcome measure includes short-term serious adverse device effect (SADE) rate and responder rate at 12 months post-implant. The study design includes an interim analysis which will occur after the 75th implanted patient reaches 12 months post-implant. If the study achieves its primary safety and effectiveness end point goals at the interim analysis, the study will be considered successful and enrollment will be stopped.2
Approved in 2013 for the treatment of medical refractory epilepsy, the RNS System remains the only brain-responsive neuromodulation system approved by the FDA. The closed-loop technology monitors and responds to a patient’s unique brain patterns to deliver therapy in real time prior to symptom onset.
"More than 1 million people are living with drug-resistant epilepsy," Steven Wolf, MD, pediatric neurologist and director, pediatric epilepsy program, Boston Children’s Health Physicians; and Patricia McGoldrick, NP, MPA, MSN, nurse practitioner and director, Pediatric Epilepsy Unit, Boston Children’s Health Physicians, said in a statement.1 “The RNS System has demonstrated unprecedented seizure reduction and improved quality of life in adults with drug-resistant focal epilepsy. Through this clinical study, we are looking forward to evaluating the RNS System in an expanded population of adolescent patients who have uncontrolled focal seizures, despite taking medications."
Since its approval, the modality has been studied in several different settings, including 2 seminal studies published in 2020. The first study, which included 150 patients with refractory epilepsy, showed median seizure reductions of 67% (IQR, 33-99) at 1 year, 75% (IQR, 50-94) at 2 years, 82% (IQR, 50-96) at 3 years or more, and 74% (IQR, 50-96) at last follow-up (mean, 2.3 years). Notably, 35% of patients treated with the device had at least a 90% reduction in seizure frequency, with 18% of patients reportedly seizure-free at last follow-up.3
The second trial was a 9-year, long-term study that included 230 patients across 34 epilepsy centers with nearly 1900 patient-implant years of follow-up. At 9 years, the median percent reduction in seizure frequency was 75% (P <.0001; Wilcoxon signed rank), the responder rate was 73%, and 35% had at least a 90% reduction in seizure frequency. Additionally, 18.4% of the cohort experienced at least 1 year of seizure freedom, with 62% of those seizure-free at the last follow-up.4
"The RESPONSE study is an exciting opportunity to evaluate the safety and effectiveness of the RNS System in a younger population aged 12 through 17 [years], when seizures can profoundly impact school, social development, and self-esteem, as well as expose the teen to all of the risks of seizures themselves," Martha Morrell, MD, chief medical officer, NeuroPace, and primary investigator of RESPONSE, said in a statement.1 "Our recent announcement of nearly 11 yearsof battery life for the RNS System is especially beneficial to younger patients—fewer replacement procedures translates into lower health risk and lower cost for patients."
RESPONSE is one of the many ongoing studies further evaluating the efficacy and safety of the RNS System. In July 2021, the National Institutes of Health granted an investigational device exemption (IDE) to study the modulation device in patients with Lennox-Gastaut syndrome.5 Months later, in November 2021, the company received another IDE to evaluate the RNS System in patients with idiopathic generalized epilepsy. Dubbed NAUTILUS, that prospective, randomized pivotal study is the first to evaluate the effects of brain-responsive neuromodulation in this patient population.6