LINX® Reflux Management System: Best Practices Meeting

Friday, May18, 2012

C. Daniel Smith, MDChair, Department of Surgery

Surgeon-in-Chief

Mayo Clinic in Florida

Establishing the LINX® System as a Surgical Offering

Disclosure

- Co-PI for one of the sites who participated in the Pivotal Trial

- Advisor/consultant to Torax for preparation of the presentation to FDA

- Joined company for presentation to FDA

- Paid consultant to company helping with safe and successful introduction of Linx to care of GERD patients

Goals for This Portion of Discussion

- I’m not going to tell anyone in audience anything that they don’t already know

- Offer perspective on current surgical treatment for GERD (Nissen fundoplication)

- Where would Linx fit in surgical practice

- What is the Linx patient

- Propose principles for use in our practices

Fundoplication

- Great operation

- Select patients do very well

- Superior to PPIs

- Significant positive impact on natural history of GERD

- Multiple studies have confirmed its effectiveness and role in treatment of GERD

Current Treatment Options for GERD N

o. G

ERD

Pati

ents

Severity of Symptoms and Dissatisfaction Mild Severe

PPI TherapyPPI Therapy

FundoplicationSurgery

FundoplicationSurgery

Fundoplication

- Use of fundoplication for GERD has peaked, use has been slowly declining

- GIs have largely stopped referring patients except for desperate or complicated cases

- Most cases are done for complicated conditions (redo, large hiatal hernia, Barretts, severe refractory GERD

- PPIs remain treatment of choice for all but the most severe cases of GERD

Fundoplication – Why Not

- Multifactorial

- Technical failures – inconsistent and questionable outcomes

- Lack of standardized approach/technique

- Inconsistent use – patients still have fundoplication performed without objective confirmation fo GERD

- Patients are afraid of the operation – troubling side-effects of gas bloat and excess flatus or perception that failure rate is 50%

- GIs refuse to refer – all of the above and/or strong belief that it is a bad operation

- Competing treatments – primarily PPIs, some endolumenal approaches

Two Predictors of Surgical Outcome

Patient Selection Operative Technique

• Patients without objective confirmation of GERD

• Patients who fail to respond to PPIs

• Patients with BMI >35

• Atypical symptoms?

• Occasional antireflux surgeon

• Patient selection can be tricky

• Defining the typical GERD patient has been difficult

• 2 stitch, three stitch, four stitch• Esophageal stitch, how many and

location• Pledgets for wrap or crural repair• Divide short gastrics or not• Anchor wrap to diaphragm/crura• Extensive esophageal mobilization• Calibrate wrap and to what size• Occasional antireflux surgeon• Tricky operation• Not everyone can get good

outcomes

Fundoplication

Current Treatment Options for GERD N

o. G

ERD

Pati

ents

Severity of Symptoms and Dissatisfaction Mild Severe

PPI Therapy

FundoplicationSurgery

Therapy Gap

No standard treatment for Gap patients

Targeted Linx population

Pivotal Trial

Key Outcomes

Summary of Efficacy Endpoints

Percent Successful (95% Binomial Exact Confidence Limits)

0 10 20 30 40 50 60 70 80 90 100

Secondary: PPI ≥ 50% reduction in daily PPI use

Secondary: GERD ≥ 50% reduction in GERD-HRQL

Primary: pH Normalization or ≥ 50% reduction

64% (:54, 73%)

92% (85, 97%)

93% (86, 97%)

Efficacy Endpoints by Baseline Hernia Assessment (≤3 cm)

Primary Efficacy Endpoint Component No Hernia All Patients

Normalization (pH<4.5%) 67% (29/43) 58.3% (56/96)> 50% reduction from baseline 77% (33/43) 63.5% (61/96)Either normalization or > 50% reduction 79% (34/43) 66.7% (64/96)

PPI Free DaysAs of Last Follow-Up

0

100

200

300

400

500

600

700

800

900

PPI F

ree

Day

s

Minimal Side Effects

Ability to Belch• 99% of patients throughout study

period

Inability to Vomit• 0% at 12 months• 1% at 24 months

Note: As actively queried by Foregut Questionnaire

Reduced Gas Bloat

Baseline 12 Month Post LINX 24 Month Post LINX0

20

40

60

80

100

Severity of Gas BloatFREQUENTLY CONTINOUSLY

Pe

rce

nt

of

Pa

tien

ts R

ep

ort

ing

Note: As actively queried by Foregut Questionnaire

Overall Acceptable Safety Risk

144 patients implanted between 2-4 years No deaths No intra-operative complications No device failures No device erosions or migrations

Serious Adverse Events

6% (8/144) No late onset (>1 year)

The Successful LINX Patient

Post-LINX% of Pts 2 Years

8%

2%

2%

1%

1%

12%

11%

Baseline% of Pts Characteristic

100% Daily PPI dependence

70% Reflux affecting their sleep on a daily basis

76% Reflux affecting their food tolerances on a daily basis

57% Moderate or severe regurgitation including aspirations

55% Severe heartburn affecting their daily life

51% Experiencing extra esophageal symptoms in addition to heartburn and/or regurgitation

40% Esophagitis

How Were Good Results Achieved

• Rigorous adherence to patient selection and standardized surgical technique (arguably, even tighter adherence to standardized surgical technique would have improved outcomes even further)

Hernia at Baseline NpH

Endpoint Success

GERD-HRQLEndpoint Success

PPI UseEndpoint Success

None 44 77% 89% 91%Yes – repaired 30 67% 100% 97%

Yes – not repaired 26 39% 89% 92%

pH Endpoint Success 95% CINo hernia or hernia repaired 73.0% (54 / 74) 61.4, 82.7%

Two Predictors of Surgical Outcome

Patient Selection Operative Technique

• Tight control on patient selection

• Don’t go after extended inclusion criteria patients

• Work closely with GI to assure full diagnostic work-up and consistent patient selection

• Consistent patient instructions to establish expectations (dysphagia is common, diet progression

• Device that results in predictable response/performance

• Standard technique for placement

• If any question of hiatal defect, approximate crura with stitch(es)

LINX

Defining the LINX® Patient

Key Pivotal IDE Eligibility Criteria

Inclusion

Age 18-75 years Typical GERD symptoms >6 months Pathologic GERD – (esophageal pH<4 for >4.5% of time) Daily PPI use Symptomatic improvement on PPIs

Exclusion

Hiatal hernia (>3cm) Esophagitis Grade C or D (LA classification) Barrett’s esophagus Esophageal motility disorder

Patient Selection Per Labeling

INDICATION

The LINX Reflux Management System is indicated for patients

diagnosed with GERD as defined by abnormal pH testing, who

continue to have chronic GERD symptoms despite

maximum medical therapy for the treatment of reflux.

Patient Selection Per Labeling

PRECAUTIONS 1. Hiatal hernia >3 cm

2. Barrett’s esophagus

3. Esophagitis grade C or D

4. Electrical implants or metallic abdominal implants

5. Major motility disorders

6. Scleroderma

7. Esophageal or gastric cancer

8. Dysphagia greater than once per week within the last 3 months

9. Esophageal or gastric surgery or endoscopic intervention

10. Distal amplitude <35 mmHg or <70% peristaltic sequences

11. Esophageal stricture or gross anatomic abnormalities

12. Esophageal or gastric varices

13. Lactating, pregnant or plan to become pregnant

14. Morbid obesity (BMI >35)

15. Age <21 years

These PRECAUTIONS are

based on the inclusion/exclusion

criteria of the pivotal study.

Patients outside of these

PRECAUTIONS have not been studied.

Extended Criteria Use

• Linx in hiatal hernia > 3 cm

• Linx in Barretts

• Linx in morbid obesity (BMI > 35)

• Linx with sleeve gastrectomy

Defining the LINX® PatientExamples

Examples

• 45 year old male• Heartburn is primary symptom• Double dose PPI for last 3 years• pH < 4.5 10%• Normal esophageal motility• Normal EGD• 2 cm sliding hiatal hernia• Completely satisfied on current PPI regimen

• LINX Patient?

Examples

• 24 year old female• Chest pain is primary symptom• Single dose PPI for last 6 months• pH < 4.5 - 6%• Normal esophageal motility• Normal EGD• Carries diagnosis of fibromyalgia• Absolutely no improvement in GERD symptoms on

PPIs

• LINX Patient?

Examples

• 51 year old male• Heartburn is primary symptom• Single dose PPI for last 10 years• pH < 4.5 - 11%• Normal esophageal motility• Normal EGD• PPI controls heartburn symptom• Recent onset of night time regurgitation• 3 cm hiatal hernia

• LINX Patient?

Examples

• 58 year old female• Heartburn is primary symptom• Double dose PPI for last 10 years• pH – Bravo has failed twice and can’t tolerate

catheter-based pH• Normal esophageal motility• Normal EGD• PPI controls most of symptoms, some breakthrough,

concerned about osteoporosis and reports of hip fracture when on PPIs

• No hiatal hernia

• LINX Patient?

Examples

• 72 year old male• Chest pain and regurgitation are primary symptoms• Double dose PPI for last 15 years• pH < 4.5 – 8%• Normal esophageal motility• EGD with irregular SCJ – biopsy with non-dysplastic

Barretts• History of short segment Barretts with – Halo

ablation 6 months earlier• PPI does not control symptoms • 3 hiatal hernia

• LINX Patient?

Examples

• 18 year old male• Chest pain and heartburn• Single dose PPI for last 2 years• pH < 4.5 – 8%• Normal esophageal motility• EGD with eosinophilic esophagitis• PPI does not control symptoms • No hiatal hernia

• LINX Patient?

Examples

• 23 year old female• Hoarseness and chronic cough are primary

symptoms• Double dose PPI for last 5 years• pH < 4.5 – 2% on PPIs, Impedence pH with non-acid

reflux episodes without correlation to symptoms• Esophageal motility with disordered peristalsis, but

70% peristaltic and body pressure of 35 mm Hg• EGD normal• PPI helps some• No hiatal hernia

• LINX Patient?

Summary / Principles

• Linx is a safe and effective tool for the management of GERD

• In carefully selected patients outcomes are excellent and reproducible across a variety of settings

• The maintenance of these good outcomes will be critical to gaining acceptance and reimbursement for this treatment option

• Tight adherence to strict work-up, selection criteria and operative technique is critical to achieving the consistent and good outcomes achieved in the Pivotal Trial and needed for the ongoing success of this offering

Summary / Principles

• We should agree as thought leaders in the field to adhere to these principles in offering Linx to our patients

• Extended inclusion criteria use should be done through agreed upon study so as to segregate data and outcomes

• if we do this we can help assure the advancement of our field through responsible introduction of new techniques to clinical practice

Discussion