results of the burst trial

Results of the Burst Trial: A Prospective, Randomized, Controlled Trial

Assessing Burst Stimulation for the Treatment of Chronic Pain

Timothy R. Deer, MD

Peter S. Staats, MD

Representing the Burst investigators

1

Disclosures• Timothy Deer is a consultant for Axonics, Bioness, St Jude Medical,

Saluda, Medtronic, Nevro, Nuvectra, Flowonix, Vertos, and Jazz – Minority Stock options: Axonics, Bioness, Nevro, Vertos, Saluda

– Previous stock options: Spinal Modulation

– Funded research by St Jude Medical, Nevro, Jazz, and Saluda

• Peter Staats is a consultant for St Jude, Medtronic Nevro, Boston Scientific – Board of Director and minority ownership: ElectroCore Medical

– Research funded by Medtronic, St Jude Medical, Boston Scientific, Saluda, Grunenthal, Nevro, and Bioness

12/23/2015 2

Caution: The Burst waveform is investigational and not available in the U.S.

Burst Investigators and Steering Committee

Principal Investigators

Kasra Amirdelfan, MD

Allen Burton, MD

Vu Dang, MD

Bart Edmiston, MD

Alain Fabi, MD

Steven Falowski, MD

Timothy Houden, MD

Rafael Justiz, MD

Christopher Kim, MD

Camden Kneeland, MD

Carroll Mcleod, MD

Gregory Phillips, MD

Julie Pilitsis, MD

Phillip Smith, DO

Alexander Taghva, MD

Edward Tavel, MD

Jacob Vella, MD

Derron Wilson, MD

Thomas Yearwood, MD

Steering Committee:

Timothy Deer, MD

Richard North, MD

Konstantin Slavin, MD

Peter Staats, MD

3

Background

12/23/2015 4

Current Neuromodulation Dynamics

• Increasing stigma and negative outcomes from long-term opioid use in chronic pain

– Diversion

– Abuse

– Overdose

• Growing evidence for improved outcomes and healthcare economics with earlier intervention

– Kumar’s last work

– NACC

• Significant opportunities for growth of Patient access:– SCS innovation– Novel stimulation modes and new anatomical targets provide

differentiation from our previous therapies

Burst Stimulation Mimics Natural Neuronal Signaling

• Burst firing is a naturally occurring signaling modality in human physiology and is interpreted differently by the nervous system1,2,3.

• Thalamic cells can fire in tonic and burst modes1.

• Thalamic burst firing considered a more potent activator of the cortex2,3

.

7

1. Jahnsen H, Llinás R. : Voltage-dependent Burst-to-tonic switching of thalamic cell activity: an in vitro study. Arch Ital Biol. 1984 Mar;122(1):73-82.

2. Harvey A. Swadlow1 & Alexander G. Gusev : The impact of 'Bursting' thalamic impulses at a neocortical synapse. Nature Neuroscience 4, 402 - 408 (2001).

3. Sherman SM : A wake-up call from the thalamus. Nature neuroscience, 2001

Current Hypothesis: Burst stimulation may exert its main effect through an ability to modulate both lateral & medial pathways4

8

Burst Stimulation

4. De Ridder D, et al. World Neurosurgery 2013.

Lateral Pathway Medial Pathway

(Ongoing Burst sub-study using PET and EEG to identify pathways during stimulation)

Artistic representation of the neuron/synapse

9

12/23/2015 10

Burst Trial Design

12/23/2015 11

Objectives• Demonstrate the safety and effectiveness of a

neurostimulation system that delivers both Burst and tonic stimulation

• Demonstrate non-inferiority of overall pain with Burst versus tonic stimulation

12

Trial Design

• Multi-center, prospective

• Randomized (1:1)

• Crossover design (each subject was their own control)

• 76 subjects required to perform primary endpoint analysis

• Each patient had a device that could deliver both tonic and Burst stimulation

13

Burst(12 weeks)

Tonic (12 weeks)

Tonic (12 weeks)

Burst(12 weeks)

Randomization

Key Exclusion Criteria:

• More than mild depression symptoms (BDI>24)

• History of substance abuse

Key Inclusion Criteria:

• Successful SCS tonic trial (>50% pain relief) system evaluation

• Chronic, intractable pain of trunk and/or limb

• Average 7-day VAS of 60 mm or higher prior to SCS tonic trial

• Stable pain medications

14

Inclusion/Exclusion

Endpoints

Secondary Endpoint

• Superiority of Overall VAS

• Superiority of Trunk VAS

• Superiority of Limb VAS

• Paresthesia coverage

• Preference15

Primary Endpoint:

• Non-inferiority of Burst: Difference in overall VAS (mm) between Burst and Tonic (within subject controls)

Consented (N=173)

Completed Tonic Evaluation (N = 121)

Randomized (N = 100)

Burst / Tonic (N = 55)

Tonic / Burst (N = 45)

Completed 24 Week Visit

(N = 85)

52 Did not meet Inclusion/Exclusion

9 Failed Tonic Trial12 Exited for Other Reasons

Consort

Subjects• Age 59.1 (± 13.5) years• 12.8 (± 10.9) years of pain• 60% Female• Conditions:

– 42% FBSS– 37% Radiculopathies

• Overall baseline VAS = 75.1 mm • Mental Health:

– Mean BDI 10.1.(±6.0) with 75% having no depression– Not clinically meaningful catastrophizing

Mean PCS 20.2 (±11.8)

17

Results

18

InferiorNon-inferioritySuperiority

Primary Endpoint: Pain Intensity

-10 -8 -6 -4 -2 0 2 4 6 8

Mean Difference of Burst VAS - Tonic VAS (mm)

Overall VAS p = 0.035; Superiority

Trunk VAS p = 0.024; Superiority

Limb VAS p = 0.044; Superiority

Preferred Therapy Type:Percentage of Patients

A significantly higher proportion of patients preferred Burst (p<0.001).

69.4%

21.2%

9.4%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Burst (n=59) Tonic (n=18) No Preference (n=8)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Eliminated or reduced No reduction

SUNBurst™ Secondary Endpoint 100% of subjects reported

paresthesia during tonic stimulation

91% of subjects reported a decrease in paresthesia during Burst relative to

tonic

65% of subjects had no paresthesia while using

Burst9%

91%

65%Eliminated

26%Reduced

Paresthesia Reduction:Burst Compared With Tonic

Reasons for Preference

1.4%

10.3%

1.4%

10.3%

3.8%

1.5%

37.5%

33.7%

0% 5% 10% 15% 20% 25% 30% 35% 40%

Other

Preferred Paresthesia

Lack of Paresthesia

Better Pain Relief

Percentage of Patients

Preferred Burst (n=59) Preferred Tonic (n=18)

Adverse Events

• No unanticipated adverse events were reported

• Similar adverse event profile to other SCS studies

• Rates similar for both stimulation modes

23

Adverse Events

Description Number of events

% Subjects

Unanticipated 0 0%

Serious Events Related to the Device or Procedures

2 1.1%

Procedure-Related 4 2.3%

Device- or Stimulation-Related 27 16.2%

Key Takeaways• Burst Stimulation provided superior pain relief vs. tonic for overall,

trunk, and limb pain

• Burst stimulation was preferred by the majority of patients (69%)

• Burst stimulation eliminated or reduced paresthesia in 91% of subjects

• There are patients who prefer paresthesia

• Each patient experienced both stimulation modes (tonic and Burst) and chose their preferred mode

25

Thank you

12/23/2015 26