FDA Panel Backs Brain Stimulator to Lower Rate of Seizures

A panel for the FDA has unanimously supported a brain stimulator that lowers the rate of seizures in people with epilepsy.

A U.S. Food and Drug Administration panel has unanimously backed a device that lowers the rate of seizures among people with epilepsy.

Smaller and thinner than an implantable defibrillator, the battery-powered, programmable device, called the RNS System, is placed just under the skull during surgery. Electrodes reach from the device to the one or two places in the patient's brain that create the abnormal electrical activity that causes seizures. The device works by short-circuiting nerve cells in that area to normalize brain activity before a seizure is triggered.

On Friday, the panel voted 11-0, with two members abstaining, to recommend approval of the system, according to MedPage Today. The FDA does not have to follow the recommendations of its expert panels, but it typically does.

"This is the first responsive neuro-stimulation system ever designed," said Frank Fischer, president and CEO of Mountain View Calif.-based NeuroPace Inc., which developed the device. "Our long-term results show that patients have a reduction of 50 percent or more in their seizure frequency, compared to baseline, and a lessening of seizure severity."

The device is designed specifically for people aged 18 and older with partial-onset epilepsy, which occurs when one or more fixed locations in a person's brain start the cascade of nerve firing that creates a seizure.

NeuroPace has done two studies involving a total of 256 patients who were monitored for a period of between two and nine years, without any significant problems, according to Fischer.

Epilepsy is a brain disorder in which a person suffers repeated seizures over time.

It affects more than 2 million Americans, according to the Epilepsy Foundation, making it the third most common neurological disorder in the United States, after Alzheimer's and stroke. Seizures are episodes of disturbed brain activity that cause changes in attention or behavior. Brain cells keep firing instead of acting in an organized way. The malfunctioning electrical system of the brain causes surges of energy that can cause a person to have muscle contractions or to black out.

Physicians can modify the programming of the device even after it has been implanted, to reflect a patient's needs over time, Fischer said. They can also observe the brain activity of a patient from a laptop computer in their office -- to help them manage a patient's treatment, he said.

Representatives of the Epilepsy Foundation said new treatments for epilepsy are sorely needed.

"We're not in a position to evaluate everything that an evaluating committee would be looking at, but we do advocate for access to treatments once they're FDA-approved," explained Angela Ostrom, vice president of public policy and advocacy for the Epilepsy Foundation, based in Landover, Md.

While Fischer said it is too soon to say what the device might cost, comparable systems for heart problems range in price from $30,000 to $35,000, not including the cost of the surgery to implant the device. The battery that powers the device lasts about three years. When it fails, a new device has to be substituted in a 30-to-60-minute outpatient surgical procedure, Fischer said.

Fischer said the company has spent 15 years developing the device.

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More about the Brain Stimulator Approved by FDA Panel

This article discusses more about the brain stimulator device that was unanimously approved by the FDA panel.

A neurological device under review by the FDA helped reduce the incidence of seizures while not greatly increasing side effects, the agency said Thursday.

The NeuroPace RNS System lowered the rate of seizures by 37.9% during a 3-month blinded evaluation period when turned on, compared with 17.3% when not turned on (P=0.012), briefing documents released ahead of an FDA advisory committee meeting showed.

"Following implant of the device and prior to initiation of stimulation, there is a reduction in seizure frequency in terms of mean or median," FDA reviewers said in the document.

The FDA's Neurological Devices Panel of the Medical Devices Advisory Committee will meet Friday to review the application of Mountain View, Calif.-based NeuroPace for approval of its RNS System for use as adjunct therapy to reduce the frequency of seizures in adults.

The RNS System is surgically implanted under the skin on the skull and records electrocorticographic (ECoG) patterns via electrodes. The device delivers short electrical pulses intended to interrupt the triggers in the brain that cause epileptic seizures.

Physicians can review ECoG recordings and assess the relationship between the device's detections and reported clinical seizures, and then adjust the RNS System's electrical pulses accordingly.

The device was studied in a randomized, double-blinded, sham-controlled trial of 191 people. Patients were required to remain on a stable anti-epileptic drug regimen; patients included in the trial had had three or more disabling seizures per month for 3 consecutive months. Roughly half the patients were randomized to have the RNS System turned on, while it remained off in the other half during a 3-month study period.

While most patients appeared to benefit from the device, there were some even in the treatment arm who worsened. "There were four subjects in the treatment group and 10 subjects in the sham group who experienced a greater than 50% increase in seizures during the blinded-evaluation period," the FDA said.

NeuroPace said 53% of patients implanted with its device experienced a 50% drop in the number of seizures 2 years after implantation.

The company also conducted a post-hoc, month-by-month analysis and found that by the end of the third month, patients with the device turned on experienced a 41.5% decrease in seizure frequency, compared with 9.4% of those who had the device off.

The FDA noted that the analysis excludes two outlying patients from the sham arm. When included in that post-hoc analysis, the efficacy difference was 40.1% versus 22.9% for the treatment and sham groups, respectively, the agency found.

The agency found that the number of adverse events -- mild and serious -- didn't differ significantly between the two trial arms. Serious adverse events (SAEs), including brain hemorrhaging and implantation-site infections, occurred in 4.2% of treatment patients and 5.4% of sham patients during the blinded evaluation period.

"Although comparable to the incidence of SAEs with other invasive intracranial procedures ... the majority of these SAEs would not be expected to occur in a comparable medically treated population with intractable epilepsy," the FDA said.

The FDA noted nine deaths in all the trials, including six from epilepsy. There were also 14 intracranial hemorrhages.

NeuroPace initially filed a marketing application with the FDA for the RNS System in July 2010, but the agency requested 12-month follow-up data on all patients in the trial. The FDA also sent a Major Deficiency Letter in June 2011 seeking clarification on statistical and clinical issues.

Although there are many approved medications for epileptic seizures, they cause significant adverse events when used in combination, the FDA said this week.

"These adverse effects can be especially problematic in vulnerable populations such as young patients still in school, those with jobs requiring cognitive skills, those operating dangerous equipment, or the elderly already on multiple drugs," the agency said.

The FDA is not required to follow the opinion of its advisory committees but usually does.

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