Current TAVR technologies - SOLACI · 14/10/2015 · Ted Feldman MD, MSCAI FACC FESC . Edwards Lifesciences SAPIEN XT Medtronic CoreValve . ACC 2015 No. at Risk Transcatheter 391

Current TAVR technologies Update on recent clinical trials

SCAI at SOLACI SOLACI-SOCIME August 7th 2015 Mexico City, DF

Ted Feldman, M.D., MSCAI FACC FESC

Evanston Hospital

Disclosure Information

The following relationships exist:

Grant support: Abbott, BSC, Edwards, WL Gore Consultant: Abbott, BSC, Coherex, Edwards, JenaValve,

Diiachi Sankyo-Lilly, WL Gore

Off label use of products and investigational devices will be discussed in this presentation

Ted Feldman MD, MSCAI FACC FESC

Edwards Lifesciences

SAPIEN XT

Medtronic CoreValve

ACC 2015

No. at Risk

Transcatheter 391 378 354 334 219

Surgical 359 343 304 282 191

18.9%

14.1%

Δ = 4.8

All-Cause Mortality

Months Post-Procedure

4

Δ = 6.5

22.2%

28.6%

Log-rank P=0.04

ACC 2015 All Stroke

5

Edwards Lifesciences

S3

Medtronic CoreValve

Evolut R

Newly Approved in the US

CoreValve Evolut R EnVeo R Delivery System

• 14 F inline sheath

• Outflow shortened and redesigned

• More consistent radial force across annulus range

• Extended skirt at inflow, less traumatic

inflow edge

• Repositionable

18FR

18FR Cook Sheath

18FR

EnVeo R

w/ InLine Sheath

~22 FR (OD) 14FR Equivalent

~4 FR Reduction

Large top-row cells

facilitate coronary

access

Edwards SAPIEN 3

Transcatheter Heart Valve

Sealing Skirt

Balloon-expandable Cobalt Chromium

Frame

20, 23, 26 and 29 mm sizes e14- 16F Sheath

6.3%

5.2%

3.7% 4.5%

3.5%

2.2% 1.6%

1.1% 1.1%

0%

5%

10%

15%

20%

P1B (TF) P1A (All) P1A (TF) P2B (TF) P2B XT (TF) S3HR (All) S3HR (TF) S3i (All) S3i (TF)

All-Cause Mortality at 30 Days Edwards SAPIEN Valves (As Treated Patients)

175 344 240 271 282 583 491 1072 947

SAPIEN SXT SAPIEN 3

PARTNER I and II Trials

Overall and TF Patients

All Strokes at 30 Days Edwards SAPIEN Valves

6.7%

5.6%

4.1% 4.3%

1.5%

2.6%

0%

5%

10%

15%

20%

P1B (TF) P1A (Overall) P2B (TF) P2B XT (TF) S3HR (Overall) S3i (Overall)

179 344 276 284 583 1076

SAPIEN SAPIEN XT SAPIEN 3

PARTNER I and II Trials

Neurologist evaluations (pre- and post)

Next Generation Valves

• Centera • Sapien 3 • CoreValve Evolut R • Jena Valve • Lotus • Venus Aortic Valve • Engager TA • Direct Flow • Trinity • Portico

• Symetis • Colibri • Inovare • Thubikar • Valve Medical • Hydra • TRISKELE • NVT Allegra Valve • MyVal • HLT • TRINITY TA

TAVR Systems with CE-Approval (2007-15)

In Trials…

Edwards Self Expanding CENTERA

• Compatible with14F eSheath

• Deployment achieved via user-controlled motorized handle

• Quick preparation system

• Flex mechanism for optimal coaxial alignment

Distal flex

Touch

deployment

The Edwards CENTERA System is an investigational device only and not for commercial sale

• Double-ring design

• Minimizes risk of PVL

• Repositionable

• Fully retrievable

• 18Fr delivery

• Fully competent during positioning

• No rapid pacing or post-dilatation

• 912 patient trial planned in US

• Randomized 2:1 vs CoreValve

leaflets

DIRECT FLOW Valve Bovine pericardial

SALUS Trial: TranScatheter Aortic Valve RepLacement System Pivotal Trial The Safety and Effectiveness of the Direct Flow Medical

Tanscatheter Aortic Valve System NCT02163850

Bovine Pericardium

Locking Mechanism

Adaptive Seal

Braided Nitinol Frame

Central Radiopaque Positioning Marker

Lotus Valve System

Feasibility Study; Acute Safety & Performance (Extreme/High Risk) N=11; single arm; 23mm valve size

Primary Endpoint: Device success (VARC-1) without MACCE Meredith et al, EuroIntervention 2014; 9(11): 1264-70

Safety & Performance Study (Extreme/High Risk) N=130; single arm; 23 & 27mm valve sizes

Primary Safety Endpoint: All-cause mortality at 30d Enrollment Complete

FDA Approval Study; Safety & Efficacy (Extreme/High Risk) N=1032; Global RCT vs. CoreValve; 23, 25 & 27mm valve sizes

Enrolling

REPRISE I

REPRISE II

REPRISE II Extension

RESPOND

CE Mark Study; Safety & Performance (Extreme/High Risk) N=120; single arm; 23 & 27mm valve sizes

Primary Device Performance Endpoint: Mean pressure gradient at 30d Meredith et al, JACC 2014

REPRISE III

Post Market Safety & Performance Study (Real World) N=1000; single arm; 23, 25 & 27mm valve sizes

Primary Endpoint: All-cause mortality at 30d & 1y Enrolling

Lotus Clinical Program

Comorbidities & Baseline Scores

Age (Years) 84.0 ± 5.2 (250) NYHA Class III or IV 77.2% (193)

Gender (Female) 52.4% (131) euroSCORE 2011 (%) 6.4 ± 6.2 (250)

Diabetes, treated 24.0% (60) STS Score (v 2.73; %) 6.5 ± 4.2 (250)

Atrial fibrillation 37.2% (93) STS Plus Score (%) 10.6 ± 7.7 (250)

Echocardiographic Measurements*

AVA (cm2) 0.7 ± 0.2 (197) LVEF (%) 53.1 ± 10.5 (126)

MR (mod/severe) 10.6% (24) Mean gradient (mmHg) 45.2 ± 13.6 (212)

AR (mod/severe) 13.3% (29) Peak gradient (mmHg) 74.7 ± 21.1 (212)

Frailty Indices Threshold 5 Meter gait speed (sec) 8.6 ± 5.2 (236) > 6

Max grip strength average (kg) 21.1 ± 11.5 (246) ≤ 18

Katz Index 5.7 ± 0.8 (247) < 6

Mini-Cognitive Assessment for Dementia 3.5 ± 1.4 (244) < 4 * Independent Core Lab assessment

Baseline Characteristics REPRISE II with Extended Cohort (N=250)

I Meredith, London Valves 2014

Lotus is an investigational device and not for sale in the US. CE mark received 2013. Information for the Lotus Valve System is for use in countries with applicable product registrations. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device.

SH-148709-AI FEB2015 Page 20

3.5 5.1 3.3

8.4

4.5 4.2

19 18.6

10.9

15.9

13.4

6.7

0

5

10

15

20

25

301-year Mortality 30-day Mortality

30-Day and 12-Month Mortality in Perspective

SAPIEN XT PARTNER II1

SAPIEN PARTNER II1

CoreValve High Risk2

CoreValve Ext Risk3

CoreValve ADVANCE4

LOTUS REPRISE II5

STS Score: 10.3 11 7.3 10.3 5.3 7.1

N: 284 276 390 489 1015 120

% o

f Pa

tien

ts

1Leon M, ACC 2013., 2Adams D, N Engl J Med 2014., 3Popma J, JACC 2014., 4Linke A, PCR 2014., 5Meredith I et al, J Am Coll Cardiol 2014;64:1339–48 (30 day), Ian Meredith, TCT 2014 (1 year). Results from different studies not directly comparable. Information provided for educational purpose only.


SH-148709-AI FEB2015 Page 21

Major/Disabling Stroke at 30 Days REPRISE II & Other TAVR Studies

3.2 3.0

3.8

5.0

1.2

2.3

3.9

1.7

0

2

4

6

8

Even

t R

ate

(%)

1PARTNER II Inop: Martin Leon, MD at ACC 2013; 2PARTNER A: Smith, et al. N Engl J Med 2011;364:2187; 3PARTNER B: Leon, et al. N Engl J Med 2014; 370: 1790-98; 4CoreValve ADVANCE: Linke A, EuroPCR 2014., 5CoreValve Extreme Risk: Popma J, JACC 2014; 63(19): 1972-81., 6Adams D, N Engl J Med 2014.,7REPRISE II: Meredith I et al, J Am Coll Cardiol 2014;64:1339–48. Results from different studies not directly comparable. Information provided for educational purpose only.

SAPIEN XT PARTNER II Inoperable1

SAPIEN PARTNER II Inoperable1

SAPIEN PARTNER

A2

SAPIEN PARTNER

B3

CoreValve ADVANCE4

CoreValve Ext Risk5


LOTUS REPRISE II7


SH-148709-AI FEB2015 Page 22

Valve in Valve Deployments TAVR Clinical Trials and Registries

1.1 0.8

3.7

2.5

1.1 1.4

2.9

4.0

2.9

5.8

3.5 3.9

0.0 0

5

% V

alve

in V

alve

Dep

loym

ent

PAR

TNER

II 4

CH

OIC

E1

PAR

TNER

II 4

PAR

TNER

I (A

and

B) 8

SOU

RC

E9

FRA

NC

E 25

TVT R

egistry6

AD

VA

NC

E2

Co

reValve

Extreme R

isk7

CH

OIC

E1

FRA

NC

E 25

Portico

CE

Trial 3

REP

RISE

II & EX

T1

0

284 121 276 2554 2307 2107 7710 996 489 120 1043 103 250

Results from different studies not directly comparable. Information provided for educational purpose only. 1 Abdel-Wahab, JAMA 2014. , 2Linke, et al. EuroPCR 2014., 3Manoharan, Presented at TCT 2014. 4Leon, et al., ACC 2013. 5Gilard, et al. NEJM 2012. 6Mack, et al. JAMA 2013. 7Reardon, et al. J Thor and Cardiovasc Surgery 2014. 8Makkar, et al. JACC 2013., 9Thomas, et al. TCT 2012. 10Ian Meredith, London Valves 2014.

N:

CoreValve SAPIEN XT SAPIEN LOTUS Portico

Moderate PVL 30 days

11.5

16.9

24.2

9

4.1

18.3

3.4

0

5

10

15

20

25

30

CoreValveExt Risk

PARTNER 2BSAPIEN

PARTNER 2BXT

CoreValve HiRisk

CHOICE XT CHOICECoreValve

SAPIEN 3

Pe

rce

nt

24.2

16.9

14.2

11.5 9.0

4.0 3.4 1.7

0.6 0

5

10

15

20

25

30

% P

atie

nts

wit

h M

od

/Sev

ere

PV

L

SAPIEN XT

PARTNER II, Inop1

SAPIEN PARTNER II Inop1

CoreValve ADVANCE2

CoreValve Extreme

Risk3


Portico

CE Study5

SAPIEN 36

Direct Flow

DISCOVER7

LOTUS REPRISE II & EXT8

N=236 N=225 N=639 N=418 N=390 N=75 N=150 N=100 N=250

1Leon M, ACC 2013, 2Linke A, PCR 2014. 3Popma J, JACC 2014; 63(19): 1972-81, 4Adams D, N Engl J Med 2014; 370: 1790-98 5Manoharan, et al. TCT 2014. 6Webb J, EuroPCR 2014. 7Schofer, JACC 2013. 8Meredith I, London Valves 2014

1 Month Moderate & Severe PVL Echo Core Lab Adjudicated Clinical Trials


SH-148709-AI FEB2015 Page 25

Aortic Regurgitation REPRISE I at 2 Years

None

Trivial

Moderate

Discharge 2 Years

No Moderate / Severe AR by Independent Adjudication

Mild

Severe

20

40

60

80

100

0

% o

f Pa

tien

ts

Paravalvular Central Paravalvular Central

n=8 n=9

n=8

n=10

n=1

n=1

n=2 n=1

n=1 n=3

Ian Meredith, TCT 2014.

26

Paravalvular Aortic Regurgitation 250-Patient Interim Analysis

Perc

ent

of

Eval

uab

le

Ech

oca

rdio

gram

s

Paravalvular AR at Baseline

Baseline (N=243)

Discharge (N=244)

None

Trace

Mild

Moderate

Severe

22.2

84.4 35.8

11.1

34.6

4.5

0

20

40

60

80

100

Core-lab Adjudicated Data

3.7 0.8

Repositioning to Resolve PVL

1st Position Reposition

Pacemaker Implantation REPRISE II with Extended Cohort (N=250)

Variable Patients

Newly implanted pacemaker 28.9% (72/249)

Baseline RBBB 27.8% (20/72)

New conduction disturbance post valvuloplasty 34.7% (25/72)

LVOT overstretch ≥10% 61.1% (44/72)

Annulus overstretch ≥10% 34.7% (25/72)

Indication Indication

3rd deg. AV block 59 LBBB & 1st deg. AV block 3

Atrial fibrillation & bradycardia 4 LBBB & 2nd deg. AV block (Type 1) 1

Trifascicular block 1 LBBB, EP study showing severe infranodal disease

3 New LBBB, symptomatic bradycardia 1

Patients Patients

I Meredith, London Valves 2014

Feasibility Study; Acute Safety & Performance (Extreme/High Risk) N=11; single arm; 23mm valve size

Primary Endpoint: Device success (VARC-1) without MACCE Meredith et al, EuroIntervention 2014; 9(11): 1264-70

Safety & Performance Study (Extreme/High Risk) N=130; single arm; 23 & 27mm valve sizes

Primary Safety Endpoint: All-cause mortality at 30d Enrollment Complete

FDA Approval Study; Safety & Efficacy (Extreme/High Risk) N=1032; Global RCT vs. CoreValve; 23, 25 & 27mm valve sizes

Enrolling

REPRISE I

REPRISE II


RESPOND

CE Mark Study; Safety & Performance (Extreme/High Risk) N=120; single arm; 23 & 27mm valve sizes

Primary Device Performance Endpoint: Mean pressure gradient at 30d Meredith et al, JACC 2014

REPRISE III

Post Market Safety & Performance Study (Real World) N=1000; single arm; 23, 25 & 27mm valve sizes

Primary Endpoint: All-cause mortality at 30d & 1y Enrolling


To evaluate the safety and effectiveness of the Lotus™ Valve System

for TAVR in symptomatic subjects with calcific, severe native aortic

valve stenosis who are considered at extreme or high risk for

surgical valve replacement

Lotus Valve CoreValve 23, 25, 27 mm sizes 26, 29, 31 mm sizes

Objective

Study Design

Study Devices

N=1032; Global, prospective, multicenter, controlled trial. 2:1 randomized vs. CoreValve.

Follow up at discharge or 7d, 30d, 6m, 1y annually through 5Y 20 mm < Aortic Annulus Size < 27 mm

REpositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus™ Valve System – Randomized Clinical Evaluation

REPRISE III Trial

Up to 60 Centers United States, Canada, Western Europe and Australia

Study Sites

1st REPRISE III Patient September 22, 2014

Feasibility (Acute Safety, High Risk) N=11; single arm; 23mm valve size

1⁰ Endpoint: Device success (VARC) without MACCE REPRISE I 2-yr f/u

TCT 2014

Post Market Study (Safety & Performance, All Comers) N=1000; single arm; 23, 25 & 27mm valve sizes

1⁰ Safety Endpoint: Mortality at 30 days & 1 year RESPOND

Enrolling: >500 pts

FDA Trial Approval (Safety & Effectiveness, High Risk & Inoperable) N=1032; Lotus (23, 25, 27mm) vs. CoreValve (26, 29, 31mm)

1⁰ Safety Endpoint – 30 days Mortality, stroke, LT/major bleed, AKIN stage 2/3 or major vasc comp

1⁰ Effectiveness Endpoint – 1 year Mortality, stroke, LT bleed, disabling stroke or mod/severe PVL

REPRISE III

Enrolling: 508 pts

(421 RCT, 87 roll in)

REPRISE II 1-yr f/u TCT 2014

CE Mark Study (Safety & Performance, High Risk) N=120; single arm; 23 & 27mm valve sizes

1⁰ Endpts: 30-day mean pressure gradient & 30-day mortality

1⁰ endpt PCR London Valves 2014

Safety/Performance (High Risk) N=130; single arm

23 & 27mm valve sizes


REPRISE II Extended Cohort N=250

1⁰ Safety Endpt: 30-day mortality

REPRISE Japan Enrolling

PMDA Trial Approval Confirm Safety & Effectiveness in Japan, High Risk & Inoperable

N=50; single arm; 23, 25 & 27mm valve sizes 1⁰ Endpoints similar to REPRISE III: safety at 30 days, effectiveness at 6 mos


31 Jul 2015

Estimated Global TAVR Growth

SOURCE: Credit Suisse TAVI Comment –January 8, 2015. ASP assumption for 2024 and 2025 based on analyst model. Revenue split assumption in 2025 is 45% U.S., 35% EU, 10% Japan, 10% ROW

An All-comers Randomized Clinical Trial Comparing Transcatheter with Surgical AVR

NOTION Randomized Trial

Mean age 79 years Mean STS 3%

NOTION 1 Year in As-Treated Population

Pulmonic Valvuloplasty Catheter

Rubio-Alvarex V, Limon R, Soni J: Intracardiac valvulotomy by means of a catheter Arch Inst Cardiol Mex 23(2):183-92, 1953

Documents

Current TAVR technologies - SOLACI · 14/10/2015 · Ted Feldman MD, MSCAI FACC FESC . Edwards Lifesciences SAPIEN XT Medtronic CoreValve . ACC 2015 No. at Risk Transcatheter 391