Neuromodulation device effective for drug-resistant focal epilepsy, 3-year data show

Key takeaways:

• Neuromodulation offers personalized, responsive treatment option for those with drug-resistant focal epilepsy.
• RNS System led to 62% reduction in median percent seizure frequency within 6 months of treatment.

Up to 40% of all epilepsy diagnoses in the United States are of the drug-resistant variety, affecting 1.2 million people nationwide.

The RNS System provides a personalized and responsive treatment option for patients with this condition, according to a release from the device manufacturer.

Healio spoke to Martha Morrell, MD, chief medical officer at NeuroPace and clinical professor of neurology and epileptologist at Stanford University, to find out more about its RNS System and the clinical trial that demonstrated its efficacy over 3 years.

Healio: What factors led to the decision that a device, rather than other kinds of therapeutics, might be an answer for drug-resistant epilepsy?

Morrell: Despite the introduction of many new antiseizure medications (ASMs) over the past 15 years, patients who do not respond to trials of two ASMs have less than a 5% chance of achieving seizure control, no matter how many trials of different ASMs follow.

For patients with seizures that arise from a discrete region of the brain, such as focal epilepsy, surgery to remove or ablate the seizure focus can achieve excellent results, even seizure freedom.

However, that is an option for only about 15% of patients with ASM-resistant focal epilepsy. Neuromodulation is another option for ASM-resistant focal epilepsy in persons who are not candidates for epilepsy surgery or do not choose to undergo a destructive procedure. The VNS, which stimulates the vagus nerve in the neck, was the first device approved to treat epilepsy. Subsequently, trials were conducted for devices that delivered stimulation directly to the brain. One device is a thalamic duty cycle stimulator (DBS) and the other is the RNS System, the first direct-brain responsive neuromodulation device. After feasibility and randomized controlled clinical trials, in 2013 the FDA approved the RNS System to treat adults with ASM-resistant focal onset epilepsy from one or two seizure foci.

Healio: How and why was the RNS System developed?

Morrell: Discussions about a responsive approach to treat epilepsy began in the late 1990s. This approach was imagined as similar to cardiac defibrillators that intervene only when an arrythmia occurs. Since epilepsy occurs because of an abnormal electrical event in the brain, and these events are infrequent, this approach made sense.

Using two leads that both sense and stimulate, containing four electrodes each, the RNS System provides stimulation at the location of seizure onset only in response to abnormal electrical activity.

The physician identifies the specific abnormal electrographic patterns to be detected, as well as the stimulation parameters. In the clinical trials, the total amount of stimulation delivered was about 3.5 minutes a day. The RNS System neurostimulator stores the location, date and time of detections of epileptiform activity, as well as samples of the intracranial EEG. This data is available for the physician’s review on a secure web-accessed database. The physician can review this data to track their patient’s response to treatment over months and years. This data is also helpful to view changes in response to medication and behavior management.

Healio: Why was the decision made for the post–approval study to last up to 5 years?

Morrell: The post-approval study (PAS) was designed in collaboration with FDA to collect clinically meaningful information about safety and effectiveness in real-world use. Since RNS System is a chronic therapy and since the response to therapy improves with time, the long-term experience is important to both physician and patient.

Healio: Can you discuss the results of the study as presented at AAN and what they portend for those living with the condition?

Morrell: An open-label, prospective PAS was required by FDA as a condition of the RNS System approval. This study was designed to provide real-world data in patients treated according to the approved indication for use.

Results of the 3-year primary effectiveness analysis and interim safety results (the primary safety analysis is at 5 years) were presented at the American Academy of Neurology in April. These data represent the largest multicenter, prospective, real-world study of neuromodulation for drug-resistant focal epilepsy to date.

A total of 324 patients were enrolled across 32 centers in the United States. Patient baseline characteristics were similar to patients participating in the earlier feasibility and randomized controlled trials.

The effectiveness of RNS System treatment in the post-approval study surpassed the experience in the early clinical trials. There was a 62% reduction in the median percent seizure frequency within 6 months of treatment and that response increased to 82% at 3 years, with 42% of patients experiencing at least one period of 6 months or longer without seizures.

This is particularly striking when considering that the average duration of medically intractable epilepsy was 17.8 years, and the median seizure frequency was six seizures per month. Effectiveness was similar across patients with one or two seizure onsets and across onset location (mesial temporal, neocortical, or both mesial temporal and neocortical).

As in the pre-approval studies, treatment was well-tolerated and safe, and the sudden unexplained death in epilepsy (SUDEP) rate was low. No serious stimulation-related adverse events were reported. Combining data from all RNS System trials (n= 645), the SUDEP rate was 2.3/1000 patient years; this is significantly lower than predefined comparators.

Healio: What are the next steps for patients and clinicians who use the device?

Morrell: As the RNS System has already secured FDA approval, it is available at most comprehensive epilepsy centers throughout the U.S.

Patients treated in the PAS met the current FDA approved indication for use and were similar in baseline characteristics to patients in the earlier trials, including characteristics related to the severity of their focal epilepsy.

Improved seizure outcomes may reflect changes in programming practices that come from experience gained in the initial clinical trials, and by learning from the brain data provided by the device.

Reference:

NeuroPace announces data from a long-term post-approval study of the RNS System in focal epilepsy at the 2025 AAN Annual Meeting. https://investors.neuropace.com/news-releases/news-release-details/neuropace-announces-data-long-term-post-approval-study-rns. Published April 8, 2025. Accessed May 4, 2025.

For more information:

Martha Morrell, MD, can be found on LinkedIn here.