Data From Pivotal Study Show Medtronic Deep Brain Stimulation Therapy Reduced Seizure Rate in Patients With Severe Epilepsy

MINNEAPOLIS – Dec. 8, 2008 – In a clinical trial supported by Medtronic, Inc. (NYSE: MDT), deep brain stimulation (DBS) significantly reduced seizure frequency among patients with medically refractory epilepsy with partial-onset seizures, a form of the neurological condition that does not respond well to antiepileptic drugs. The study, known as SANTE® (Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy), is the only prospective, randomized, double-blind pivotal study to evaluate the use of Medtronic DBS for epilepsy. The findings were presented at the American Epilepsy Society (AES) Annual Meeting in Seattle by Robert Fisher, M.D., professor of neurology and director of Stanford Epilepsy Center (Editor-in-Chief of epilepsy.com) and principal investigator for the SANTE study.

The results from the SANTE study showed that stimulating the left and right anterior nucleus of the thalamus – the brain’s central message and relay station – with Medtronic’s DBS therapy for epilepsy in conjunction with epilepsy medications produced a statistically significant median percent reduction in seizures compared to a no stimulation control group at the end of the blinded phase of the study (38 percent in the treatment groups vs. 14.5 percent in the control group with both groups continuing on their epilepsy medications without change during this phase). The results from long-term follow up during the trial show even greater reductions in seizures for the majority of patients. Key data highlights:

• Of the 87 study participants who completed the diaries through month 13, 40 percent experienced a 50 percent or greater reduction in their baseline rate of seizures 13 months after implant.
• Of the 86 study participants who had at least three months of data from long-term follow up, 60 percent experienced a 50 percent or greater reduction in their baseline rate of seizures. These long-term follow up results represent outcomes from the last three months of available data for each patient (ranged from 12 to 49 months after implant with median follow up of 31 months).
• During this same long-term follow-up period (last three months of data for each patient), median seizure frequency was reduced by approximately two-thirds, nine percent of study participants had no seizures and 19 percent experienced a greater than 90 percent reduction in seizure frequency.

“Approximately one-third of patients with epilepsy have uncontrollable seizures with little or no response to medications, surgery or other treatments, which has a significant impact on their quality of life,” said Dr. Fisher. “Based on the seizure frequency results from the SANTE study, DBS may become a promising treatment option for appropriate patients.”

The types of adverse events reported in the study were consistent with known adverse events associated with epilepsy and implanted DBS systems. There were no serious unanticipated device-related adverse events. Twenty-two percent of the total reported events were related to stimulation, hardware or procedure and three percent of all adverse events were serious device-related effects. The infection rate was 10.9 percent and the rate of asymptomatic intracranial hemorrhage was 1.3 percent per lead implant. While there was a significantly higher incidence of spontaneously self-reported depression, memory impairment, and anxiety in the active group compared to the control group during the blinded phase, most events resolved spontaneously or with changes in medication or stimulation parameters. Objective neuropsychological assessment at the end of the Blinded Phase did not confirm any statistical differences between the active and control groups.

Patients in the study have had epilepsy for an average of 22 years and 54 percent of the 110 implanted patients had previously undergone resective surgery and/or vagal nerve stimulation therapy. Benefit also was seen in patients with prior history of vagal nerve stimulation or previous epilepsy surgery. The study is still ongoing with some patients having received DBS therapy for more than four years.

About SANTE

The study collected data from 110 patients from 17 U.S. centers who were implanted with a DBS system and were monitored for a minimum of 13 months following implant. Study participants had partial-onset epilepsy, had failed to see benefit from at least three antiepileptic drugs and had an average of six or more seizures per month. All patients continued to receive epilepsy medications while participating in the study. Patients in the study’s active stimulation group received neurostimulation and were monitored for a reduction in seizure rates compared to the control group, who received a DBS implant but received no neurostimulation during the three-month double-blind phase. After the three-month, double-blind phase, all patients received neurostimulation within pre-defined parameters (physicians could choose to make one adjustment to a specified voltage OR frequency at two specified time points) for nine months, followed by a long-term follow up phase where they continued to receive neurostimulation and physicians were allowed to change stimulation parameters. Long-term results reported at the AES meeting represented the results from the last three months of available data for each patient, some of whom have remained on the study for more than four years (range from 13 to 49 months).

Based on the results of this study, Medtronic plans to submit a premarket approval (PMA) application to the U.S. Food & Drug Administration (FDA) seeking approval for Medtronic DBS Therapy for epilepsy.

“We are very encouraged by the SANTE trial results, which demonstrated a positive response with DBS in patients who have had very severe epilepsy for an average of 22 years,” said Rick Kuntz, M.D., president of the Neuromodulation business and senior vice president at Medtronic. “This study reinforces our commitment to exploring other applications for DBS. In this case, we believe these data show promise for patients who have not been able to achieve adequate control of their seizures with medications.”