Results reported for clinical trial for the treatment of depression using external trigeminal nerve stimulation

Earlier today, at the American Psychiatric Association Annual Meeting in Philadelphia, Dr. Ian Cook, Principal Investigator and Professor of Psychiatry at UCLA, and a Senior Medical Advisor to NeuroSigma, Inc., presented the results of a Phase Ib open-label clinical trial that studied the effects of eTNS™ on depressive symptoms in Major Depressive Disorder (MDD) as an adjunct to pharmacotherapy. Results from the 17-question Hamilton Depression Rating Scale (HDRS-17), a clinician-rated scale, showed a 50.0% reduction in depression and the Beck Depression Inventory (BDI), a self-reported scale, showed a 58.0% reduction in scores. Both scales achieved statistical significance. In the trial, subjects placed stimulating eTNS™ electrodes on their foreheads for 8 hours each night and their depression was measured every two weeks using recognized standard tests. eTNS was well tolerated and no serious adverse events occurred during the 8-week treatment period.

The 11-subject study was conducted at the University of California, Los Angeles (UCLA). A previous initial report of the first five subjects also found positive results. "These findings confirm our preliminary observations that eTNS can impact symptoms in pharmacoresistant major depression. The participants in the study told us that it was easy to use at home, and most noticed that they were feeling substantially better within the first two weeks, with even more improvement in the subsequent weeks. As a result of these findings, a Phase II clinical trial, to test this potential adjunctive therapy under double-blind conditions, is being conducted at UCLA with funding provided by NeuroSigma. I'm confident that the transfer of the technology from academia to industry will continue to proceed smoothly and hope this treatment will be made available to many patients in the near future," Dr. Cook said.

This Phase Ib study was an open-label clinical trial of eTNS™ therapy in adults with non-psychotic unipolar MDD that had lasted more than 4 months and had not responded to at least one antidepressant, with a median of 4 medication failures. Clinical improvements were consistently found across several different ways to measure symptom burden.

The TNS technology, including eTNS™ for the treatment of depression, was invented and originally developed at UCLA. NeuroSigma, Inc., a Los Angeles-based medical technology company established to in-license and develop early stage technologies with the potential to transform medical practice, is the exclusive worldwide licensee of UCLA's TNS intellectual property. "We are extremely pleased to be working closely with Dr. Cook and his talented and dedicated team at UCLA,” said Dr. Leon Ekchian, President and CEO of NeuroSigma. “We look forward to helping make his vision of a safe, non-invasive, non-pharmacological therapy for depression available to patients worldwide."

NeuroSigma has completed development of its external TNS (eTNS™) system and is developing its implantable subcutaneous TNS (sTNS™) system. Once approved by regulatory agencies, patients who respond well to eTNS™ can opt to switch to the implantable sTNS™ system. Near term milestones include filing a CE Mark application in mid-2012 for approval to commence marketing the eTNS system for the treatment of epilepsy and depression in Europe, and in the second-half of 2012, NeuroSigma is planning to file an IDE with the FDA for a multi-center epilepsy Phase III pivotal trial in the United States.

Background – TNS

NeuroSigma’s eTNS™ system is a non-invasive therapy, which utilizes a self-adhesive conductive pad applied to the forehead to stimulate branches of the trigeminal nerve, which are located very close to the surface of the skin of the forehead. The trigeminal nerve is the largest cranial nerve, offering a high-bandwidth pathway for signals to enter the brain. In clinical studies, eTNS™ is well tolerated and the low-energy stimulus is confined to the soft tissues of the face without penetration into the brain. The trigeminal nerve projects to specific areas of the brain, such as the locus coeruleus, nucleus tractus solitarius, thalamus and the cerebral cortex, which are involved in epilepsy, depression, PTSD and other disorders. PET imaging studies in humans confirm that eTNS™ modulates activity in key regions implicated in these disorders and the changes were observed within minutes of therapy.

CAUTION: Both eTNS™ and sTNS™ systems are investigational devices and at this time are limited by Federal (or United States) law to investigational use.

About NeuroSigma, Inc.
NeuroSigma is a Los Angeles-based medical technology company established to develop early stage technologies with the potential to transform medical practice. Currently, NeuroSigma is focused on a number of neuromodulation therapies and, through its majority-owned subsidiary, NSVascular, Inc., on Thin-Film Nitinol covered stents for endovascular applications. NeuroSigma employs two neuromodulation therapy platforms: Trigeminal Nerve Stimulation (TNS) and Deep Brain Stimulation (DBS). NeuroSigma has amassed significant intellectual property licensed on an exclusive basis from the University of California, Los Angeles (UCLA), including potential therapies for epilepsy, depression, post-traumatic stress disorder (PTSD) and attention-deficit hyperactivity disorder (ADHD) via TNS and for PTSD, obesity and cachexia via DBS.