Abstracts

Rationale: The RNS™ System (NeuroPace®,Inc.) is an investigational device being tested as an adjunctive therapy for adults with medically intractable partial onset seizures. The RNS™ System includes a cranially implanted programmable responsive neurostimulator connected to depth and/or subdural leads, a physician programmer, a patient data transmitter and a web based interactive data repository. A two-year multi-center feasibility trial collected safety and efficacy data after implantation of the neurostimulator and leads. Subjects were then able to transition into a 5-year long-term treatment trial to gather additional safety and efficacy data. Longer term efficacy and safety data as of April 20, 2008 are presented. Methods: Subjects were 18-65 years of age with intractable partial-onset seizures localized to one or two epileptogenic onset region(s). Subjects with >12 simple partial (SP) sensory or motor seizures, complex partial seizures (CPS) and/or generalized tonic-clonic (GTC) seizures over an 84-day baseline period qualified for implantation of the neurostimulator and leads. Efficacy was assessed over the 84 days beginning one month after implantation of the neurostimulator and leads (primary), over the most recent 84 days of participation, and over the entire period of participation. Adverse events (AEs) were monitored throughout the trial. Results: During the primary evaluation period, the responder rate (RR= % of subjects with a 50% or greater reduction in seizures) in 50 subjects (excluding 1 subject with no disabling seizures at baseline and 14 subjects randomized to off) was 27% (12/44) for CPS, 65% (11/17) for GTC, and 24% (12/50) for total disabling seizures (TDS= SP motor, CPS and GTC). For the secondary evaluation over the most recent 84 days of participation, the RR was 74% (14/19) for subjects with seizure onsets in the hippocampus, 37% (15/41) for seizure onsets in the neocortex and 48% for all 60 subjects combined (excluding 1 subject with no disabling seizures at baseline and 4 subjects with incomplete or inconsistent seizure frequency data). The RR for TDS for all subjects increased from 25% at 3 months of treatment (n=64), to 48% at 18 months (n=61) and to 54% for the 27 subjects for whom there was 36 months of data. In the 65 implanted subjects representing over 180 patient years of stimulation, there were no serious unanticipated device-related AEs, and responsive neurostimulation was well tolerated. Conclusions: A feasibility and long-term treatment investigation of the RNS™ System demonstrated safety and a sustained reduction in disabling seizures. Preliminary results indicated that the RNS™ System might provide a safe and effective adjunctive treatment for adults with intractable partial-onset epilepsy. A multi-center randomized double blinded pivotal trial is currently underway.