High-Frequency Spinal Cord Stimulation Therapy in Failed Back Surgery Syndrome Patients with Predominant Back Pain Adnan Al-Kaisy1, Jean-Pierre Van Buyten2, Stefano Palmisani1, Thomas Smith1, Iris Smet2 1St Thomas' hospital, London, United Kingdom, 2AZ Nikolaas, St Niklaas, Belgium

Disclosure Study supported by grant from Nevro Corp (Menlo Park, CA) CAUTION – Nevro’s Senza™ system is an investigational device limited by Federal (USA) law to investigational use. The device is approved for use in the European Union.

Most common locations of chronic pain 5% 8% 24% 15% 9% 6% 18% 16% 14% 8%

Introduction FBSS: Each year, more than 1 million spinal surgeries are performed in the US with 400,000 cases being instrumented. 1 Roughly half of these are in the lumbosacral area. 2 Despite surgery, approximately 30% of these patients fail to improve, as shown by persistent back pain. 2 SCS: Traditional SCS is a well-accepted option for Failed Back Surgery Syndrome (FBSS) patients with predominantly neuropathic leg pain. 1, 2 However, providing adequate and sustained back pain relief for patients with predominant back pain remains more challenging. 1, 2 1 Frey, Manchikanti, Benyamin, et al. Spinal Cord Stimulation for Patients with Back Surgery Syndrome: A Systematic Review. Pain Physician. 2009; 12:379-397. 2 Van Buyten JP, Linderoth B. “The Failed Back Surgery Syndrome”: Definition and therapeutic algorithms: An Update. Eur J of Pain Suppl. 2010;4:273-286.

High-Frequency SCS Senza High-Frequency SCS system is a novel SCS system allows pulse rate up to 10 kHz. Surgical technique similar to traditional SCS, however, a useful difference: Traditional SCS requires intraoperative paresthesia mapping Potentially uncomfortable for patient Can lead to wide range in procedure times HF-SCS lead positioning is more efficient: No paresthesia mapping needed Anatomically positioned Overlapping leads along midline  Shorter, more predictable procedure times

High-Frequency SCS & FBSS Senza was evaluated for use in the treatment of chronic pain in a prospective, open label study. 3 The study trialed 83 patients with or without prior surgery The study demonstrated the safety and efficacy of the novel therapy A subset analysis was conducted for the FBSS subset This subset includes 67 patients The patients were followed-up to 12 months 3 Van Buyten et al, High-Frequency Spinal Cord Stimulation for the Treatment of Chronic Back Pain Patients: Results of a Prospective Multicenter European Clinical Study. Neuromodulation. Accepted for publication

Baseline Demographics Mean age in years 49.6 ± 9.5 Gender 54% Female Mean years since back pain diagnosis 10 Predominant back pain 91% Failed traditional SCS 18% VAS Back (SD) 8.4 ( 1.2) VAS Leg (SD) 5.4 ( 3.2) Mean # of prior surgeries (range) 2 (1-5) History of back surgery: spinal fusion discectomy laminectomy disc replacement 52% 42% 40% 13% mean number of back surgeries: 2 (range: 1-5)

Trial Results 57/66 patients (86%) had successful trial (> 50% pain relief) and went to permanent implant. Notable results given significant number of difficult-to-treat patients: 91% of FBSS cohort had predominant back pain, which doesn’t respond well to traditional SCS 18 % of FBSS cohort previously failed traditional SCS Note: 1 patient did not complete the trial

Average Visual Analog Scale (VAS) for Pain Pain Relief at 12 Months Average Visual Analog Scale (VAS) for Pain (mean + SEM) Significant and sustained back pain & leg pain relief despite difficult-to-treat population. 70% of the patients had ≥ 50% back pain relief at 12 months. N=57 N=57 N=54 p < 0.001 p < 0.001 Note: Subjects who have successfully passed the trial and received permanent implant

Improved Function at 12 Months Average Oswestry Disability Index (mean + SEM) Severe disability Sustained reduction in disabilities. 15 point decrease in ODI at 12 months. Low disability N=56 N=56 N=53 p < 0.001 p < 0.001

Excellent Safety Profile Device related Serious Adverse Events were consistent with standard SCS practice: There were no therapy-related neurological findings. No device had to be explanted due to battery life issues. SAE Number of Events Pocket Pain 4 Wound Infection 3 Lead Migration 2 Loss of Pain Relief 1 Suboptimal Lead Placement

Summary & Conclusions Despite advances in traditional SCS (i.e. transverse tripole, triangular stimulation, etc), providing relief to FBSS patients with predominant axial low back pain remains very difficult. This 67 patient analysis of High-Frequency SCS on FBSS patients shows: High trial success rate despite difficult to treat patients (91% of the cohort had predominant back pain) 86% trial phase success rate Significant and sustained relief for both back pain and leg pain 70% responder rate at 12 months Sizeable and durable improvement in function 15 point reduction in ODI at 12 months HF-SCS should be considered as a leading therapeutic option for FBSS patients (even those with predominant back pain) The “Holy Grail” of SCS has been the relief of low back pain Anatomical and technological issues have made consistent paresthesiae difficult. These issues have led to the development of newer techniques and technologies (e.g. peripheral field stimulation, transverse tripole stimulation, etc. CAUTION – Nevro’s Senza™ system is an investigational device limited by Federal (USA) law to investigational use. The device is approved for use in the European Union.