NeuroPace (NASDAQ:NPCE) said the U.S. Food and Drug Administration determined that its premarket approval supplement seeking to expand the RNS System indication to patients with medication-resistant idiopathic generalized epilepsy, or IGE, was not approvable in its current form.
The company said the FDA requested additional information regarding the clinical evidence supporting the submission. NeuroPace President and Chief Executive Officer Joel Becker said management believes there is a path to approval and is working with the agency to address remaining questions.
FDA Seeks Additional Clinical Context
NeuroPace plans to submit a Submission Issue Request, or SIR, to discuss its proposed response with the FDA before filing an amendment to the PMA supplement. Becker said the company expects to meet with the agency in the coming weeks and believes the process can help align the parties on the content and structure of the supplemental package.
The proposed amendment is expected to include additional analyses from the NAUTILUS trial, real-world evidence and further context regarding the clinical meaningfulness of seizure reductions. The FDA also requested the complete 24-month dataset from the study, according to Chief Medical Officer Dr. Martha Morrell.
Morrell said the agency is particularly interested in analyses of patients with different baseline frequencies of generalized tonic-clonic, or GTC, seizures, as well as more detailed patient-reported outcomes, stimulation programming information and published literature on the impact of GTC seizures.
“They want to consider the totality of the evidence,” Morrell said, adding that the agency is seeking to better understand whether the observed benefits extend across patient subgroups rather than being driven by a particular subset of participants.
No New Safety Concerns Identified
Becker said the FDA’s determination was not based on a new safety issue. The NAUTILUS trial met its primary safety endpoint, and the FDA communication did not identify new safety signals associated with the RNS System, according to the company.
NAUTILUS was a prospective, multicenter, randomized, single-blind, sham stimulation-controlled study evaluating responsive thalamic stimulation with the RNS System in patients with drug-resistant IGE. While its primary effectiveness endpoint did not achieve statistical significance, NeuroPace said prespecified additional analyses comparing seizure frequency during treatment against baseline showed statistically significant improvements.
At 18 months, patients treated with the RNS System experienced a median 77% reduction in GTC seizures from baseline, while 40% of patients were free of GTC seizures at that time point, Morrell said. More than 90% of patients reported improvement on the Patient Global Impression of Change, while 80% of physicians reported improvement on the Clinical Global Impression of Improvement.
The company also cited an approximately 30% reduction in seizure-related injury events and 44% lower odds of benzodiazepine rescue-medication use for a GTC seizure. NeuroPace said the 18-month results have been peer reviewed and published in Epilepsia.
Among evaluable patients who completed 24-month post-implant follow-up and received stimulation for 23 of 24 months after implantation, the median reduction in GTC seizures was 100% from baseline, according to Morrell. She said 41 patients had data through 23 months of stimulation, while 84 patients had data covering some period of stimulation.
Timing Remains Subject to FDA Review
Following an SIR meeting, NeuroPace expects to file an amendment if it reaches alignment with the FDA on the needed clinical evidence. The FDA will determine the review classification for that amendment and could treat it as a major amendment, extending the review period by as much as 180 days.
Becker said the company currently expects that its amendment could be reviewed without restarting the full 180-day clock, citing the RNS System’s Breakthrough Device Designation, the interactive discussions with the agency and the FDA’s handling of prior amendments during the review. He said NeuroPace would provide more detailed timing after the SIR meeting.
The company said its full-year 2026 financial guidance did not include revenue from a potential expanded IGE indication. NeuroPace plans to report financial results and provide any updates to its outlook during its Aug. 11, 2026, earnings conference call.
About NeuroPace (NASDAQ:NPCE)
NeuroPace, Inc is a medical device company based in Mountain View, California, that develops innovative neuromodulation systems for the treatment of neurological disorders. Founded in the late 1990s out of research at Stanford University, the company’s mission centers on delivering closed-loop, “smart” therapies that monitor and respond to electrical activity in the brain. In 2020, NeuroPace completed its initial public offering and now trades on the NASDAQ under the ticker NPCE.
The company’s flagship product, the RNS® System, is an implantable device designed for adults with medically refractory focal epilepsy.
