L Liem , M.D. F Huygen, M.D., Ph.D Marc Russo , M.D. JP Van Buyten , M.D. I Smet, M.D.

1. Effects of Spinal Cord Stimulation of the Dorsal Root Ganglion (DRG) in the Treatment of Chronic, Intractable Pain: Long-Term Results from Two Prospective Clinical Trials L Liem, M.D. FHuygen, M.D., Ph.D Marc Russo, M.D. JP Van Buyten, M.D. I Smet, M.D. Paul Verrills, M.D. Professor Michael Cousins, M.D. RajSundaraj, M.D. CharlesBrooker, M.D. NANS 2012

2. Disclosures • Philips • Boston Scientific • Spinal Modulation • Caution:  The Spinal Modulation Axium™ Spinal Cord Stimulator System is currently an investigational device in the United States and is not approved for use in the United States. 

3. Spinal Cord Stimulation Targeting the Dorsal Root Ganglion • Specialized delivery system for efficient access to the foramen • Small, flexible leads have been designed specifically for stimulation of the DRG • Small, non-rechargeable neurostimulator designed to complement the lead and system Conventional Lead DRG Lead

4. Clinical Study Design Success? no Baseline Trial Screen Fail • 2 prospective clinical trials • Sites in Europe and Australia enrolled subjects • N=32 subjects implanted with Spinal Modulation Axium™ Spinal Cord Stimulator System • Primary and secondary outcome measures captured • Two (2) on-off periods to demonstrate “rebound” pain Stimulation turned off yes 3-30 days 8 weeks* 3 months 6 months 1 year Baseline Implant 1 week 4 weeks 1 week off Stimulation turned off Trial Exit

5. Study Outcomes Primary • Efficacy was determined by Visual Analog Scale (VAS) • Both overall pain and regional (“segmented”) VAS scores were collected over time based upon primary, secondary and/or tertiary areas of pain • Safety was evaluated by collecting adverse events during the course of the trial Secondary • Health Related Quality of Life (HR-QoL) – EQ-5D • Profile of Mood States (POMS) • Brief Pain Inventory (BPI) • Subject Satisfaction • Paresthesia Intensity with Changes in Bodily Position

6. Subject Diagnoses

7. Primary outcomes Visual Analog Scores (VAS)

8. Primary Outcomes – Overall Pain Relief 60% reduction at 12 months VAS (mm) n=32 n=32 n=30 n=24 n=24 n=24 n=17

9. Primary Outcomes – Leg Pain* 66% reduction at 12 months VAS (mm) n=25 n=25 n=24 n=19 n=22 n=19 n=13 * Diagnoses include CRPS, Post-Surgical Pain, FBSS, Radicular Pain

10. Primary Outcomes – Foot Pain* 82% reduction at 12 months VAS (mm) n=13 n=13 n=13 n=9 n=12 n=10 n=6 * Diagnoses include CRPS, Post-Surgical Pain, FBSS

11. Assessing Rebound Pain after Stimulation is Turned Off 1 week No Stim 1 week No Stim

12. Less Lead Migration than traditional SCS • Stimulation leads for SCS of the DRG reported <3% migration rates. • Traditional SCS (PROCESS trial) reports migration rate of 10%.1 1 Kumar, et al, Pain, 2007

13. Secondary outcomes

14. Limited Changes in Paresthesia Intensity N=22

15. Therapeutic targeting: Specific & Painful Regions Painful Regions Paresthesia • Example representations of painful regions and areas of therapeutic coverage. • Paresthesias could be generated in both discrete and broad coverage zones. • Most paresthesias were generated over the painful regions with little extraneous paresthesias in non-painful regions.

16. EQ-5D: Independent Outcomes Baseline 6 months

17. Brief Pain Inventory- Overall Outcomes Significant improvements in both Pain Interference and Pain Severity measures (*p<0.05)

18. Profile of Mood States: POMS Outcomes

19. Conclusions • Clinical data from European and Australia clinical trials show that the Axium™ SCS System can provide significant long-term pain relief in CRPS, Post-Surgical Neuropathies, and FBSS • Body positions (standing versus supine) did not affect the intensity of paresthesia and is stable over 12 months • Stimulation can be isolated to specific anatomical regions such as the foot and leg • Therapy is stable long term with less than 3% lead migration • Secondary measures of quality of life, mood and activity are all improved complimenting the reductions in pain.

20. Thank you