An FDA advisory panel last week debated who should be allowed to implant NeuroPace’s anti-epilepsy device, where it should be implanted and which patients should be eligible for it on the way to recommending approval for the implant.
The federal watchdog agency’s Neurological Devices Advisory Panel, in a non-binding vote Feb. 22, recommended that the FDA approve NeuroPace’s RNS deep-brain stimulation therapy for certain categories of epilepsy, but had some reservations about the details
"The majority of the panel said, yes there is likely a sub-population that will benefit more and maybe a sub-population that might benefit less, but we can’t identify it based on data we’ve heard today," acting chairwoman Dr. Lynda Yang, of the University of Michigan’s Dept. of Neurosurgery, told MassDevice.com. "The population that might benefit more, we’ve heard 1 suggestion: High frequency of seizures. There is also concern that this type of device should be limited or offered in epilepsy centers, where things like studying the distance from seizure focus and all that later on can take place."
The panel voted unanimously on Friday that the RNS implantable neurostimulator demonstrated safety in clinical trials. Twelve of 13 panelists voted that the device demonstrated reasonable effectiveness; 11 of 13 voted that the benefits outweigh the risks. There were no negative votes from the panel, with 1 member abstaining on the question of effectiveness and 2 abstaining from the question of the risk-benefit ratio.
NeuroPace hopes to win FDA approval for the 1st-of-its-kind RNS system as an adjunctive therapy to reduce the "frequency of seizures in individuals 18 years of age or older with partial onset seizures from no more than 2 foci that are refractory to 2 or more anti-epileptic medications," according to the company.
The RNS device is surgically implanted in the cranium, where it senses and records electrocorticographic patterns from intra-cranial electrodes. The device delivers short trains of electrical energy to the brain to interrupt dangerous activity indicative of a seizure.
The RNS implant’s detection and stimulation parameters can be tuned to optimize seizure control against stimulation-related side effects. The device can also be programmed using a wide range of different detection algorithms and responsive stimulation outputs, according to the FDA.
The device continuously records brain activity. Data captured immediately before and after a storage trigger event (such as abnormal electrical activity) is retained for review by a physician and periodically uploaded to an online database. Physicians can use the data to look for patterns in detections, reported seizures and the effects of stimulation.
Current epileptic seizure treatments with known benefits and lower risk than the RNS device include drug therapy and vagus nerve stimulation, another neurostimulation implant therapy that sends small pulses of electrical energy to the brain via the vagus nerve in the neck. Mesial temporal resection surgery is another option.
Panel debates specifying who can give & receive the implant
UCLA Seizure Disorder Center’s Dr. Jerome Engle stressed the need to clarify which patients might benefit most from an RNS device in a post-approval study.
"This is a very invasive procedure, and [even] if there are a lot of patients who could benefit from it, it needs to be used carefully," he said. "The VNS experience taught us that a lot of patients went for VNS who really shouldn’t have, and who should have been referred for surgery and weren’t.
But several panelists pointed out that the RNS device is indicated for patients who have failed on 2 or more medications.
"Asking people to continue on best medical therapy when the indication for the device is failure of medical therapy is outrageous," said Dr. Stephen Haines of the University of Minnesota’s Dept. of Neurosurgery. "It will take some thought, but there are creative ways, some of which have been mentioned, to come up with a therapy group."
Most panelists thought that asking NeuroPace to conduct a 10-year follow-up is unreasonable and generally agreed instead on a 2-to-5-year post-approval study.
Engle urged that if approved, the RNS device should only be used at level 4 epilepsy centers that do epilepsy surgery.
"[It] ought to be a criterion that it only be done in places that do epilepsy surgeries, so that this wouldn’t be done in people who might be candidates for surgery and don’t realize it," he said.
Dr. Richard Fessler of the Northwestern Medical Faculty’s Dept. of Neurosurgery disagreed that specific language is needed to restrict who can implant the device.
"The mechanisms for training neurologists and neurosurgeons in how to do this and who to do it to and where to do it are in place," he said. "We don’t have to re-create the wheel.
"Secondly, if I’m lucky enough to catch my flight tonight, I have no intention of telling the pilot how to fly my plane," Fessler added. "By the same logic, I think it unwise for any individual group or organization that doesn’t do this every day to try and tell the most highly skilled and educated physicians in this field how to do their job."
The placement of the RNS device’s electrodes is "critical if this device is approved and is going to be useful," Engle responded. Those best suited to evaluate which patients are most likely to benefit from the surgery should be the same people who do evaluation for epilepsy surgery, he said.
"It would be a disaster if this gets in the hands of people who want to use it in every rural hospital around the country," Engle said. "So I would approve this only if there were some way to regulate its use to people who could use it properly."
The FDA rejected NeuroPace’s original 2010 PMA application on the grounds that the company failed to provide 12-month follow-up on data on all study subjects, which the agency had requested in the RNS device’s investigational device exemption.
The FDA issued a "Not Filing" decision July 26, 2010. NeuroPace filed a PMA for the RNS device the following November, after submitting an amendment with 12-month data on all subjects.
The FDA responded with a "Major Deficiency" letter June 14, 2011, seeking clarification on clinical and statistical issues. NeuroPace provided additional information. The agency asked the advisory panel whether the data provided was enough to approve RNS based on a reasonable assurance of the safety and effectiveness of the RNS system for its intended use.