[PPT] - Introduction Winx TM (OPT) Device OPT has been shown to effectively PowerPoint Presentation

SLIDE 1

2/15/2014 1

Oral Pressure Therapy for OSA

Richard J. Schwab, M.D. Professor of Medicine Division of Sleep Medicine Pulmonary, Allergy and Critical Care Division University of Pennsylvania Medical Center Philadelphia, Pennsylvania

Oral Pressure Therapy for OSA - Disclosures

NIH grants - RO1/PPG (Obesity and OSA)
Consultant:
Apnicure - WinxTM device
Foramis Medical Group

WinxTM (OPT) Device

Console Mouth Piece

A novel oral pressure therapy (OPT) system (WinxTM,

ApniCure, Inc.) provides negative pressure to the oral cavity

Introduction

OPT has been shown to effectively treat sleep

apnea in about 40% of patients (Colrain IM et al. Sleep Medicine 14; 830–837, 2013)

SLIDE 2

2/15/2014 2

AHI and ODI: Responder Cohort (n=26) AHI by Severity: Analysis Cohort (n=63)

Examining the Mechanism of Action of a New Device Using Oral Pressure Therapy for the Treatment of Obstructive Sleep Apnea

Schwab et al, submitted to sleep (conditionally accepted)

WinxTM Device

Study Objectives and Design

Objective of the study was to explore the

mechanism of action of the OPT (oral pressure therapy) device

Case series study of 15 responders (13 men, 2

women) and 4 nonresponders (3 men) with sleep

apnea. In the responders the mean AHI was 38.5 ±

23.3 events/hour before the OPT device was applied and was reduced to 6.7 ± 5.0 events/hour with the OPT device

All subjects underwent a MRI to examine the

biomechanical changes associated with the OPT device

SLIDE 3

2/15/2014 3

Hypotheses

With the application of oral pressure therapy (OPT):

Mean, minimum and maximum airway area in

the retropalatal region would increase

Retropalatal anterior-posterior and lateral

airway dimensions would increase

Retroglossal airway dimensions would not

change

3-dimensional centroid of the soft palate and

anterior segment of the tongue would move anteriorly and superiorly

Demographic Information for OPT Subjects

Characteristic Responders (n=15) Non-Responders (n=4) p* Age, mean ± SD 58.1 ± 7.7 48.0 ± 8.2 0.1133 BMI, mean ± SD 30.9 ± 4.0 32.9 ± 3.6 0.2621 Male, N (%) 13 (87%) 3 (75%) 0.5304 AHI at Baseline, mean ± SD 38.5 ± 23.3 24.3 ± 19.4 0.2208 AHI on Device, mean ± SD 6.7 ± 5.0 27.9 ± 24.0 0.0093 AHI Change, mean ± SD

31.9 ± 20.2

3.6 ± 14.9 0.0059

*p-value from Fisher’s exact test (for categorical variable) or Wilcoxon two-sample exact test (for continuous variables) comparing responders and non-responders

Methods: OPT Application

Magnetic Resonance Imaging (1.5T) During wakefulness and supine

Baseline Device, No Suction Device @ 20 inches H2O

3D Image Analysis

BASELINE WITH OPT

SLIDE 4

2/15/2014 4

Results - Retropalatal Airway Change with OPT

BASELINE WITH OPT

% Change Between Baseline and Device with 20 inches H2O

Minimum Airway Area: 116% Improvement (69 mm2 Baseline | 149.3 mm2 Device) Maximum Airway Area: 20% Improvement (290.8 mm2 Baseline | 347.9 mm2 Device) Yellow lines indicate minimum retropalatal airway (lateral dimension) at baseline

Airway Percent Changes the Retropalatal Region for OPT Device Responders

Percent Change Measure Baseline vs. OPT0* OPT0 vs. OPT20† Baseline vs. OPT20* Mean ± SD p‡ Mean ± SD p‡ Mean ± SD p‡ Average Retropalatal Airway Area Per Slice (mm2) 23.46 ± 51.81 0.1040 31.7 ± 37.98 0.0067 56.48 ± 65.63 0.0023 Retropalatal Maximum A/P Distance (mm)

2.20 ± 15.13

0.5417 7.69 ± 8.34 0.0081 7.4 ± 17.23 0.0419 Retropalatal Maximum Cross- Sectional Area (mm2) 8.30 ± 29.34 0.2958 66.84 ± 71.02 0.0001 78.31 ± 94.31 0.0002 Retropalatal Maximum Lateral Distance (mm) 3.28 ± 16.58 0.5879 7.59 ± 12.22 0.0574 10.81 ± 16.39 0.0295 Retropalatal Minimum A/P Distance (mm) 2.16 ± 41.47 0.4143 16.11 ± 29.64 0.0681 17.48 ± 63.51 0.3910 Retropalatal Minimum Cross- Sectional Area (mm2) 5.87 ± 38.60 0.9515 51.96 ± 74.78 0.0085 60.93 ± 88.64 0.0419 Retropalatal Minimum Lateral Distance (mm)

2.00 ± 15.08

0.6848 11.65 ± 16.53 0.0215 6.64 ± 10.89 0.0419

*Change calculated with respect to baseline; †Change calculated with respect to OPT0; ‡p- value from non-parametric signed rank test

Airway Percent Changes the Retropalatal Region for OPT Device Responders and Non-Responders

Percent Change Baseline vs. OPT0* OPT0 vs. OPT20† Baseline vs. OPT20* Measure Mean ± SD p‡ Mean ± SD p‡ Mean ± SD p‡ Responder Non- Responder Responder Non- Responder Responder Non- Responder Average Airway Area Per Slice (mm2) 23.46 ± 51.81 0.05 ± 0.83 0.2327 31.70 ± 37.98

1.28 ±

0.87 0.0614 56.48 ± 65.63

1.24 ±

0.22 0.0078 Maximum A/P Distance (mm)

2.20 ± 15.13

2.15 ± 2.42 0.4118 7.69 ± 8.34

6.17 ±

5.62 0.0059 7.40 ± 17.23

4.12 ±

6.88 0.1013 Maximum Cross- Sectional Area (mm2) 8.30 ± 29.34

0.86 ±

1.91 0.3275 66.84 ± 71.02

1.07 ±

2.14 0.0007 78.31 ± 94.31

1.91 ±

3.06 0.0078 Maximum Lateral Distance (mm) 3.28 ± 16.58 2.21 ± 5.29 0.8706 7.59 ± 12.22

1.12 ±

5.00 0.2454 10.81 ± 16.39 0.88 ± 1.93 0.0464 Minimum A/P Distance (mm) 2.16 ± 41.47 1.38 ± 5.77 0.4773 16.11 ± 29.64

2.86 ±

3.04 0.0597 17.48 ± 63.51

1.64 ±

2.96 0.3275 Minimum Cross- Sectional Area (mm2) 5.87 ± 38.60

1.05 ±

2.16 0.7980 51.96 ± 74.78

3.53 ±

5.00 0.0346 60.93 ± 88.64

4.61 ±

3.61 0.1575 Minimum Lateral Distance (mm)

2.00 ± 15.08
1.1 ±

10.15 0.9563 11.65 ± 16.53 4.42 ± 6.80 0.3504 6.64 ± 10.89 2.93 ± 7.85 0.3817

*Change calculated with respect to baseline; †Change calculated with respect to OPT0; ‡p-value from non-parametric Wilcoxon two-sample exact test, comparing changes in responders vs. non- responders

Airway Percent Changes the Retroglossal Region for OPT Device Responders

Percent Change Measure Baseline vs. OPT0* OPT0 vs. OPT20† Baseline vs. OPT20* Mean ± SD p‡ Mean ± SD p‡ Mean ± SD p‡ Average Retroglossal Airway Area Per Slice (mm2)

20.08 ± 28.71

0.0203

17.68 ± 23.91

0.0203

36.53 ± 19.15

0.0001 Retroglossal Maximum A/P Distance (mm)

19.66 ± 13.85

0.0006 2.65 ± 14.95 0.4973

18.23 ± 14.27

0.0009 Retroglossal Maximum Cross- Sectional Area (mm2)

9.48 ± 27.78

0.1937

14.03 ± 29.70

0.1189

25.83 ± 20.54

0.0004 Retroglossal Maximum Lateral Distance (mm)

0.35 ± 18.59

>0.999

13.92 ± 21.07

0.0419

13.36 ± 25.03

0.0353 Retroglossal Minimum A/P Distance (mm)

30.46 ± 16.17

0.0002 5.76 ± 24.07 0.6257

26.76 ± 22.50

0.0031 Retroglossal Minimum Cross- Sectional Area (mm2)

30.93 ± 32.95

0.0052

9.23 ± 32.70

0.3575

44.85 ± 21.17

0.0001 Retroglossal Minimum Lateral Distance (MM)

18.8 ± 30.77

0.0295

6.19 ± 55.73

0.1189

33.86 ± 24.46

0.0002

*Change calculated with respect to baseline; †Change calculated with respect to OPT0; ‡p-value from non-parametric signed rank test

SLIDE 5

2/15/2014 5 Airway Percent Changes the Retroglossal Region for OPT Device Responders and Non-Responders

Percent Change Baseline vs. OPT0* OPT0 vs. OPT20† Baseline vs. OPT20* Measure Mean±SD p‡ Mean±SD p‡ Mean±SD p‡ Responder Non- Responder Responder Non- Responder Responder Non- Responder Average Airway Area Per Slice (mm2)

20.08 ±

28.71

35.63 ±

6.57 0.5739

17.68 ±

23.91 19.24 ± 71.44 0.5052

36.53 ±

19.15

26.68 ± 33.91

0.5965 Maximum A/P Distance (mm)

19.66 ±

13.85

5.81 ± 0.84

0.1013 2.65 ± 14.95 7.63 ± 1.12 0.7849

18.23 ±

14.27 1.38 ± 1.39 0.0118 Maximum Cross- Sectional Area (mm2)

9.48 ±

27.78

4.42 ±

10.28 0.7209

14.03 ±

29.70 3.54 ± 11.94 0.1575

25.83 ±

20.54

1.95 ± 2.32

0.0196 Maximum Lateral Distance (mm)

0.35 ±

18.59

0.32 ± 3.89

0.9588

13.92 ±

21.07

2.98 ± 2.29

0.1922

13.35 ±

25.03

3.31 ± 4.07

0.3571 Minimum A/P Distance (mm)

30.46 ±

16.17

6.58 ± 3.99

0.0078 5.76 ± 24.07 9.73 ± 8.78 0.7980

26.76 ±

22.50 2.33 ± 6.29 0.0093 Minimum Cross- Sectional Area (mm2)

30.93 ±

32.95

6.09 ± 9.08

0.0464

9.23 ±

32.70

5.21 ± 11.7

0.7980

44.85 ±

21.17

11.61 ± 7.08

0.0062 Minimum Lateral Distance (mm)

18.80 ±

30.77

1.71 ± 6.95

0.2327

6.19 ±

55.73

1.58 ± 4.42

0.0791

33.86 ±

24.46

3.43 ± 4.92

0.0485

*Change calculated with respect to baseline; †Change calculated with respect to OPT0; ‡p-value from non- parametric Wilcoxon two-sample exact test, comparing changes in responders vs. non-responders

Baseline Treatment

Soft Palate Anterior Tongue Soft Palate Anterior Tongue

Results - Soft Tissue Effect with OPT

Oral pressure therapy (OPT) treatment moved the 3-dimensional centroid of the soft palate anteriorly 12.9 ± 4.1 mm and superiorly 10.0 ± 3.6 mm Oral pressure therapy (OPT) treatment moved the centroid of the anterior segment

f

the tongue forward, towards the teeth, 7.8 ± 3.3 mm

Changes in the 3 Dimensional Centroid of the Anterior Quadrant of the Tongue and 3 Dimensional Centroid of the Soft Palate for OPT Device Responders

Difference Measure Baseline vs. OPT0* OPT0 vs. OPT20† Baseline vs. OPT20* Mean ± SD p‡ Mean ± SD p‡ Mean ± SD p‡ Anterior Tongue Section: Anterior Displacement (mm)

2.42 ± 3.27

0.0134

4.87 ± 3.74

0.0007

6.52 ± 3.90

0.0002 Anterior Tongue Section: Superior Displacement (mm)

4.03 ± 3.25

0.0012 4.62 ± 2.42 0.0002 0.58 ± 2.18 0.4631 Soft Palate: Anterior Displacement (mm)

3.55 ± 2.54

0.0002

8.54 ± 3.38

0.0002

10.96 ± 5.42

0.0002 Soft Palate: Superior Displacement (mm) 8.95 ± 1.59 0.0002 7.23 ± 7.04 0.0017 15.31 ± 7.37 0.0001

*Change calculated with respect to baseline; †Change calculated with respect to OPT0; ‡p-value from non-parametric signed rank test

Changes in the 3 Dimensional Centroid of the Anterior Quadrant of the Tongue and 3 Dimensional Centroid of the Soft Palate for OPT Device Responders and Non-Responders

*Change calculated with respect to baseline; †Change calculated with respect to OPT0; ‡p-value from non-parametric Wilcoxon two-sample exact test, comparing changes in responders vs. non-responders

Difference Baseline vs. OPT0* OPT0 vs. OPT20† Baseline vs. OPT20* Measure Mean ± SD p‡ Mean ± SD p‡ Mean ± SD p‡ Responder Non- Responder Responder Non- Responder Responder Non- Responder Anterior Tongue Section: Anterior Displacement (mm)

2.42 ± 3.27
0.10 ± 3.18

0.7034

4.87 ±

3.74

0.89 ±

3.24 0.1017

6.52 ±

3.90

0.99 ±

1.98 0.0078 Anterior Tongue Section: Superior Displacement (mm)

4.03 ± 3.25
0.19 ± 1.46

0.0227 4.62 ± 2.42 1.15 ± 1.48 0.0445 0.58 ± 2.18 0.96 ± 1.55 0.6451 Soft Palate: Anterior Displacement (mm)

3.55 ± 2.54

0.30 ± 5.08 0.1017

8.54 ±

3.38

7.35 ±

7.31 0.2958

10.96 ±

5.42

7.04 ±

2.98 0.0614 Soft Palate: Superior Displacement (mm) 8.95 ± 1.59 2.17 ± 4.98 0.0319 7.23 ± 7.04 2.61 ± 2.23 0.2958 15.31 ± 7.37 4.79 ± 6.45 0.0248

SLIDE 6

2/15/2014 6

Measurement and Results

Oral pressure therapy significantly increased the

size of the retropalatal airway in both the lateral and anterior-posterior dimensions by moving the soft palate anteriorly and superiorly and the anterior-superior segment of the tongue forward, towards the teeth

In the retropalatal region there were significant

increases in the mean, maximum and minimum cross-sectional areas with the OPT device

However, in the retroglossal region airway caliber

decreased with the OPT device

Conclusions

Oral pressure therapy (OPT), a novel treatment for sleep

apnea, increases the size of the retropalatal airway by moving the soft palate anteriorly and superiorly and the anterior segment of the tongue forward, towards the teeth

OPT increases airway caliber in both the anterior-

posterior and lateral dimensions

This treatment did not increase the size of the

retroglossal airway

Our data suggest that patients manifesting an enlarged

soft palate or exhibiting retropalatal airway collapse would be ideal candidates for OPT therapy

Winx+ (adds a tongue retaining device WINX

Next Generation

Winx+

SLIDE 7

2/15/2014 7

Feasibility Study of Winx+ Mouthpiece

Subjects: 25 OSA patients naïve to Winx with AHI > 15 events/hour Protocol:

Baseline full night PSG off therapy
Full night PSG on Winx+ device followed

by 4 nights use at home

.

Results of Feasibility Study #2: 25 Subjects to Date

AHI Baseline Winx+ 37.8 19.3

16/25 (64%) had a > 50 reduction in AHI and final AHI < 20
16/25 (64%) had a > 50 reduction in AHI and final AHI < 15
13/25 (52%) had a > 50 reduction in AHI and final AHI < 10

Baseline, Winx, and Winx+ from the Sagittal View

Baseline Winx Winx+

In this subject, the Winx device creates little to no change in the retropalatal region of the airway, while Winx+ creates more space behind the the soft palate increasing airway volume in the retropalatal region. The yellow arrows represent the Winx suction mechanism; the red arrow represents the tongue protrusion allowed for with Winx+.

Baseline, Winx, and Winx+ from the Axial View (Retropalatal Airway)

In this subject, the Winx device creates little to no change in the retropalatal region of the airway, while Winx+ creates more space behind the the soft palate increasing airway caliber in the retropalatal region. CSA = cross-sectional area

Baseline airway CSA = 95.2 mm2 Winx airway CSA = 105.3 mm2 Winx+ airway CSA = 231.9 mm2

SLIDE 8

2/15/2014 8

Baseline Winx Winx+

Anterior Tongue Anterior Tongue Anterior Tongue Soft Palate Soft Palate Soft Palate Device Device

Thank you for your attention! Any Questions?

rschwab@mail.med.upenn.edu