First in man Studies in a novel, unique and disruptive technology to surgicaly treat Reflux desease (GERD) without anatomical changes by laparoscopic implant of leads on the esophagi-gastric junction (EGJ) followed by stimulation of a pace=maker

1. Leonardo Rodriguez, MD, Chile
Manoel Galvao Neto, MD, Brazil
VK Sharma, MD,USA
Edy Soffer, MD, USA
Shai Policker, USA
Treatment of GERD
ELECTROSTIMULATION OF
LOWER ESOPHAGEAL ESPHINCTER

2. GASTROESOPHAGEAL REFLUX DISEASE (GERD)
What is GERD (acid reflux)?
 Reflux of gastric contents
from the stomach into the
esophagus
Causes
 Hypotensive LES
 Transient LES
Relaxation (tLESR)
Lower Esophageal
Sphincter Open
Allowing for Reflux
Esophagus
Stomach
Pyloru
s
LES
Sphincter
Closed
Diaphragm
Liquid
Castell et al. American Journal of Gastroenterology, 2002; 97-575

3. GASTROESOPHAGEAL REFLUX DISEASE (GERD)
Treatment of GERD
 Life style modification
 Antacids and H-2 Blockers,
PPIs
 Nissen Fundoplication Surgery
 Relatively invasive
 Can require continued
medications1
 Hard to convert
Castell et al. American Journal of Gastroenterology, 2002; 97-575
Lower Esophageal
Sphincter Open
Allowing for Reflux
Esophagus
Stomach
Pyloru
s
LES
Sphincter
Closed
Diaphragm
Liquid

4. GERD Is Common
 GERD is a commonly diagnosed GI disorder1
 Prevalence in Brazil is 12%4
 The prevalence of GERD in the US is estimated at 30 million2
1. Richter JE. Gastroesophageal reflux disease and its complications. In: Feldman M et al, eds.
Gastrointestinal and Liver Disease. 8th ed. Philadelphia, Pa: Saunders; 2006:905-936.
2. Sandler RS et al. Gastroenterology. 2002;122:1500-1511.
3. US Census Bureau. State and County QuickFacts. 2008.
4. GUIDELINES FOR THE DIAGNOSIS AND MANAGEMENT OF GASTROESOPHAGEAL REFLUX
DISEASE: an evidence-based consensus, Arq Gastroenterol, v. 47 – no.1 – jan./mar. 2010
Epidemiology
People With GERD
million2
Population of New York City
million3
People With Refractory GERD

5. Nearly 40% of Patients on Once-Daily PPI Therapy
Have Breakthrough Symptoms
Patient-Reported Symptoms on Once-Daily
PPI Therapy (N=1064)
Proton Pump Inhibitor (PPI) Failure
American Gastroenterological Association. GERD Patient Study: Patients and Their Medications. Harris Interactive Inc;
2008.
No Breakthrough Symptoms
Breakthrough
Symptoms
New Studies highlight negative effects of long-term PPI

6. ElectroStimulation of LES
ANIMAL STUDIES
Laparoscopic (2008) / Endoscopic (2007)

7. LES Electrical Stimulation
Animal Studies
 Effect of electrical stimulation of the LES on LES pressure
 Canine model
Sanmiguel, et al (Cedar) AJPGI 2008

8. LES Electrical Stimulation
Animal Studies
 An endoscopically implantable device stimulates the LES
 on demand by remote control:
 a study using a canine model
Clarke, et al (Hopkins) Endoscopy 2007

9. ENDOSTIM NEUROSTIMULATOR TECHNOLOGY

10. ENDOSTIM NEUROSTIMULATOR TECHNOLOGY

11. ENDOSTIM NEUROSTIMULATOR TECHNOLOGY

12. ENDOSTIM NEUROSTIMULATOR TECHNOLOGY
Source: El Mercurio - Chile

13. ElectroStimulation of LES
FIRST IN MAN ACUTE STUDY
Acute Proof of Concept Study (2010)

15. “Off response”
“On response”
“Off response”
“On response”
How smooth muscle cells
works in esophagus…..

18. ElectroStimulation of LES
FIRST IN MAN CHRONIC STUDY
Open Label Study (2011)

20. Twenty-four patients treated for 6m or longer
Primary Endpoints:
Safety: No device related AE
Functionality: 100% detection of supine and treatment delivery
Secondary Endpoints:
Clinically significant improvement in all parameters:
 LES pressure and esophageal function (evaluated using HRM)
 Esophageal acid exposure
 Esophagitis healing
 GERD HRQL / patient symptoms
 PPI usage
CE-Mark Study Results
Single Arm, Treatment only protocol

21. ENDOSTIM IMPLANT

22. ENDOSTIM IMPLANT

23. ENDOSTIM IMPLANT

24. Clinically Significant Increase in LES Pressure
* p<0.005 compared to baseline
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
0 12
N=24 *
N=24
Baseline Month 3
End Exp.
Pressure
mmHg

25. SUSTAINED INCREASE OF LES PRESSURE
IDEN
TIAL
v. Interim results, not fully monitored
Time Post Implant (weeks)

26. SUSTAINED ENHANCEMENT IN LES
PRESSURE

27. PRESERVED SWALLOW FUNCTION
Baseline On Treatment

28. SUSTAINED DECREASE IN ESOPHAGEAL ACID EXPOSURE
IDEN
TIAL
p<0.001 vs. baseline (n=23)
pH Analysis Results Following Blinded Audit Performed by an Independent Expert Reviewer

29. SUSTAINED DECREASE IN ESOPHAGEAL ACID
EXPOSURE
IDEN
TIAL
p<0.001 vs. baseline (n=23)
pH Analysis Results Following Blinded Audit Performed by an Independent Expert Reviewer

30. 24-h Esophageal Acid Exposure
Baseline
% 24h pH<4.0 =13.8%
12 Weeks
% 24h pH<4.0 =0.7%

31. CONFIDENTIAL
Sustained Improvement in symptoms
* Interim data not fully monitored.
Results at each time point are given as mean ± SE
* p<0.001 vs. baseline; n=24 † p<0.005 vs. week 4, n=23
* †
****
*
On PPI BaselineOff PPI Baseline

32. * Interim data not fully monitored.
Results at each time point are given as mean ± SE
* p<0.001 vs. baseline; n=24 † p<0.005 vs. week 4, n=23

33. REDUCTION of REFLUX EVENTS
IDEN
TIAL
55% reduction in the number of total reflux events
52% drop in the number of long events (>5min), 57% drop in number of short events
All results are highly statistically significant (p<0.001)
* Interim data not fully monitored.

34. Clinically Significant Healing of Esophagitis

36. ElectroStimulation of LES
1 YEAR CHRONIC STUDY
Open Label Study (2012)

42. Lap Fundoplication
Endoscopic
Stim
Lap Stim

43. Leonardo Rodriguez, MD, Chile
VK Sharma, MD,USA
Edy Soffer, MD, USA
Shai Poliker, USA
Manoel Galvao Neto, MD, Brazil
Treatment of GERD
ELECTROSTIMULATION OF
LOWER ESOPHAGEAL ESPHINCTER