NeuroPace Submits PMA Application for FDA Approval of Novel Investigational Device for Epilepsy
Pivotal Trial Data Demonstrate RNS System Met Primary Endpoints by Significantly Reducing Seizures with Positive Safety Profile
MOUNTAIN VIEW, CA - July 8, 2010 NeuroPace, Inc. today announced that it has submitted its Premarket Approval (PMA) application to the U.S. Food and Drug Administration (FDA) for its RNS® System, a novel investigational device that utilizes responsive neurostimulation to monitor and interrupt abnormal electrical activity in the brain before seizures occur. The PMA application is for an indication to treat people with medically refractory partial onset epilepsy originating from one or two locations in the brain. Partial onset epilepsy is a common form of the disorder that is difficult to treat with medication. Results from the company's pivotal trial were included in the PMA application. The data, some of which were presented at the American Epilepsy Society's (AES) 63rd Annual Meeting in December 2009, were collected from 191 people with medically refractory partial onset epilepsy enrolled at 31 sites located in the United States. The results demonstrate the RNS System significantly reduced the frequency of disabling seizures.
"The clinical data support that this unique technology can provide an effective method to significantly reduce seizure frequency with a positive safety profile for people with partial onset epilepsy," said David Roberts, MD, Chief of Neurosurgery at Dartmouth-Hitchcock Medical Center. "Epilepsy is an extremely challenging disorder to treat and despite our best efforts, there is a large population of people who do not respond well to the currently available treatment options. The RNS System has the potential to meaningfully improve quality of life for many people who are currently living with uncontrollable seizures."
The RNS System continuously monitors brain electrical activity and, after identifying a preprogrammed abnormal pattern, delivers brief and mild electrical stimulation with the intention of suppressing the seizure before symptoms occur.
"The RNS System is the world's first responsive neurostimulation system," said Frank Fischer, CEO of NeuroPace. "We look forward to working with the FDA during the review process, and firmly believe the RNS System has the potential to provide an invaluable additional treatment option for people living with epilepsy."
The pivotal trial is a randomized, double-blind, sham stimulation controlled investigation of patients with partial onset epilepsy that previously had failed to achieve seizure control with two or more antiepileptic drugs. The primary effectiveness endpoint was to demonstrate a significantly greater reduction in seizure frequency in the treatment group (responsive stimulation on) compared to the sham stimulation group (responsive stimulation off) during the three month blinded evaluation period. Based on the statistical method prespecified in the clinical protocol (general estimating equations (GEE)), the reduction in seizure frequency over the blinded evaluation period was 37.9 percent in the treatment group compared to a 17.3 percent reduction in the sham stimulation group. This was statistically significant with a P value of 0.012. Also based on the GEE method, the treatment group experienced a 41.5 percent reduction in seizure frequency compared to only a 9.4 percent reduction in the sham group by the third month of the blinded evaluation period. For those subjects who had already reached two years post-implant, 53 percent experienced a 50 percent or greater reduction in seizures.
Importantly, the reduction in seizures with responsive stimulation was clinically meaningful as demonstrated by significant improvements in quality of life. At one and two years after implant, there were statistically significant improvements not only in overall quality of life but also in a number of subsets of quality of life including language, memory, attention/concentration, work/drive/social function, seizure worry and health discouragement.
The trial also demonstrated a serious adverse event rate less than comparative surgical procedures. There were no serious unanticipated device related adverse events reported in the trial, and there was no difference between the treatment and sham stimulation groups when comparing the rate of adverse events, including depression, memory impairment and anxiety.
About the RNS System
The RNS System is designed with novel technology to detect abnormal electrical activity in the brain and then deliver small amounts of electrical stimulation to suppress the abnormal activity before any seizure symptoms occur. This type of treatment is called responsive stimulation and differs from the continuous or intermittent stimulation provided by commercially available neurostimulation systems. With the RNS System, physicians have the ability to non-invasively program the detection and stimulation parameters of an implanted RNS Neurostimulator to customize therapy for individual patients.
About the RNS System Pivotal Clinical Trial
Trial Patient Population
The RNS System Pivotal Clinical Investigation is a randomized, double-blind, sham stimulation controlled investigation that included 191 people implanted with the RNS System across 31 sites. All subjects in the study were required to be 18 or older and have partial onset epilepsy, with seizures that start from one or two areas of the brain, that has not been effectively treated with two or more antiepileptic medications alone or in combination.
Primary Effectiveness Endpoint
The primary effectiveness objective for this investigation was to demonstrate that the reduction in seizure frequency of patients randomized to receive responsive stimulation (treatment group) was significantly greater than that experienced by patients randomized to receive sham stimulation (sham stimulation group). This was assessed using generalized estimating equations (GEE), the pre-specified method agreed upon with the FDA in the clinical protocol. The GEE method was selected because there is a wide range of seizure frequency in the patient population and the GEE method allows for analysis of longitudinal (repeated measures) data and accounts for variability across the population.
Patients in the study were implanted with the RNS System once eligibility criteria were met. The blinded evaluation period of the trial began eight weeks after the RNS System was implanted and lasted 12 weeks. Half the participants were randomly assigned to have responsive stimulation activated and half had responsive stimulation remain inactive. Participants and one doctor (assessment physician) at each site in the trial did not know whether the stimulation was active or not. A separate doctor (treatment physician) at each site programmed the device for people in the treatment group and performed sham programming for people in the sham stimulation group in order to maintain the blind. Five months after the RNS System was implanted, which is when the double-blinded portion of the trial was completed, stimulation was activated for all participants in the trial. This portion of the trial, which produced long term data, is called the open label period. Each participant will be evaluated in the pivotal trial for two years after being implanted with the RNS System. After completing the pivotal trial, participants have the option to enroll in a subsequent trial designed to gather an additional five years of safety and efficacy data.
NeuroPace was founded to design, develop, manufacture and market implantable devices for the treatment of neurological disorders by responsive brain stimulation. The company's initial focus is the treatment of epilepsy, a debilitating neurological disorder affecting approximately one percent of the population worldwide. An estimated 30-40 percent of the 50 million people worldwide (including more than 3 million Americans) experience uncontrolled seizures. In addition to treating epilepsy, responsive neurostimulation holds the promise of treating several other disabling medical disorders that impact the quality of life for millions of patients around the world.
Located in Mountain View, California, NeuroPace is a privately-held company with approximately 90 employees.
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