Eletro Stimulation of Lower Esophageal Sphincter on GERD treatment

Leonardo Rodriguez, MD, Chile

Manoel Galvao Neto, MD, Brazil

VK Sharma, MD,USA

Edy Soffer, MD, USA

Shai Policker, USA

Treatment of GERD

ELECTROSTIMULATION OFLOWER ESOPHAGEAL ESPHINCTER

GASTROESOPHAGEAL REFLUX DISEASE (GERD)

What is GERD (acid reflux)?

Reflux of gastric contents from the stomach into the esophagus

CausesHypotensive LESTransient LES

Relaxation (tLESR)

Lower Esophageal Sphincter Open Allowing for Reflux

Esophagus

Stomach

Pylorus

LES Sphincter Closed

Diaphragm

Liquid

Castell et al. American Journal of Gastroenterology, 2002; 97-575

GASTROESOPHAGEAL REFLUX DISEASE (GERD)

Treatment of GERDLife style modificationAntacids and H-2

Blockers, PPIsNissen Fundoplication

SurgeryRelatively invasiveCan 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

Pylorus

LES Sphincter Closed

Diaphragm

Liquid

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

30

Population of New York City million3

8.2

People With Refractory GERD 10million2

Nearly 40% of Patients on Once-Daily PPI Therapy Have Breakthrough Symptoms

Patient-Reported Symptoms on Once-DailyPPI 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

62% Breakthrough Symptoms

38%

New Studies highlight negative effects of long-term PPI

ElectroStimulation of LES

ANIMAL STUDIESLaparoscopic (2008) / Endoscopic

(2007)

LES Electrical StimulationAnimal Studies

Effect of electrical stimulation of the LES on LES pressure

Canine model

Sanmiguel, et al (Cedar) AJPGI 2008

LES Electrical StimulationAnimal 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

ENDOSTIM NEUROSTIMULATOR TECHNOLOGY

ENDOSTIM NEUROSTIMULATOR TECHNOLOGY

ENDOSTIM NEUROSTIMULATOR TECHNOLOGY

ENDOSTIM NEUROSTIMULATOR TECHNOLOGY

Source: El Mercurio - Chile

ElectroStimulation of LES

FIRST IN MAN ACUTE STUDYAcute Proof of Concept Study (2010)

“Off response”

“On response”

“Off response”

“On response”

How smooth muscle cells works in esophagus…..

ElectroStimulation of LES

FIRST IN MAN CHRONIC STUDYOpen Label Study (2011)

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 ResultsSingle Arm, Treatment only protocol

ENDOSTIM IMPLANT

ENDOSTIM IMPLANT

ENDOSTIM IMPLANT

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

SUSTAINED INCREASE OF LES PRESSURE

CONFIDENTIAL

v. Interim results, not fully monitored

Time Post Implant (weeks)

SUSTAINED ENHANCEMENT IN LES PRESSURE

PRESERVED SWALLOW FUNCTION

Baseline On Treatment

SUSTAINED DECREASE IN ESOPHAGEAL ACID EXPOSURE

CONFIDENTIAL

p<0.001 vs. baseline (n=23)pH Analysis Results Following Blinded Audit Performed by an Independent Expert Reviewer

SUSTAINED DECREASE IN ESOPHAGEAL ACID EXPOSURE

CONFIDENTIAL

p<0.001 vs. baseline (n=23)pH Analysis Results Following Blinded Audit Performed by an Independent Expert Reviewer

24-h Esophageal Acid Exposure

Baseline % 24h pH<4.0 =13.8%

12 Weeks % 24h pH<4.0 =0.7%

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

* 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

REDUCTION of REFLUX EVENTS

CONFIDENTIAL

55% reduction in the number of total reflux events52% 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.

Clinically Significant Healing of Esophagitis

ElectroStimulation of LES

1 YEAR CHRONIC STUDYOpen Label Study (2012)

Lap Fundoplication

Endoscopic Stim

Lap Stim

Invasiveness

Leonardo Rodriguez, MD, Chile

VK Sharma, MD,USA

Edy Soffer, MD, USA

Shai Poliker, USA

Manoel Galvao Neto, MD, Brazil

Treatment of GERD

ELECTROSTIMULATION OFLOWER ESOPHAGEAL ESPHINCTER