FDA granted a Breakthrough Device Designation to the NeuroPace® RNS® System to evaluate whether responsive CM stimulation could provide safe and effective long-term treatment for the approximately 30% of persons with drug-resistant IGE and GTCs.

Patients were implanted with the RNS neurostimulator and bilateral CM depth leads, then randomized 1:1 to active or sham responsive stimulation. Sham patients transitioned to active stimulation after their second GTC.  Primary endpoints were serious device-related adverse events over 12 weeks post-implant (safety) and time-to-second GTC (efficacy). Prespecified secondary endpoints were frequency of GTCs, days with GTCs and days with any generalized seizure at 12 and 18 months.

Eighty-seven patients were implanted with the device (23 U.S. sites); 84 completed 12 and 80 completed 18 months.  Median implant age was 28 years (range 14-66), median epilepsy duration was 17.7 years (1-54), median GTCs/month was 1.67 (0.33-24) and median concurrent antiseizure medications was 3 (1-8).

The primary safety endpoint was met (p <0.0001). The primary efficacy endpoint (time to second GTC) was not met. However, a modified analysis using 1 year data according to randomization group showed a 62% reduction in GTC frequency in the active group, which was 27% greater than sham (p=0.0111). There were clinically and statistically significant reductions in frequency of GTCs, days with GTCs and days with any generalized seizure at 12 and 18 months (both p < 0.001).

In this first-ever multicenter device RCT of drug-resistant IGE, responsive CM stimulation was safe and achieved significant, rapid, and sustained reductions in numbers and in days with GTCs and in days with any generalized seizure over 12 and 18 months.