current and future perspectives from cordis cardiology ... · current and future perspectives...

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Current and Future Perspectives Current and Future Perspectives from Cordis Cardiologyfrom Cordis Cardiology::

Building Upon the Standard of Care and ComparisonBuilding Upon the Standard of Care and Comparison

David E. Kandzari, MD, FACC, FSCAIDavid E. Kandzari, MD, FACC, FSCAIChief Medical OfficerChief Medical OfficerCordis CorporationCordis Corporation

[email protected]@crdus.jnj.com

Note: Presentation not intended as a promotion of off-label use of products

22

Finding the Path Through DES Trials is Becoming Increasingly Difficult

• Global medical community recognizes RCTs as highest level of evidence– ACC/AHA/ESC ‘Level A Evidence’

• Both RCTs and non-RCTs have purpose– RCT: balanced comparison of ≥2 therapies

• Limit: Restrictive inclusion criteria may apply– Registry: outcomes of therapy in ‘real world’ practice

• Limit: biases preclude accurate comparisons, despite propensity scores, adjustment; follow-up often less precise, especially in subgroups

• Rapid increase in single- and multi-center observational registries outnumbering RCTs– Probability alone enables variable and unexpected

results

33

The CYPHER® Stent Clinical Trials Program: A Higher Level of Evidence

• Most extensive (>45,000 pts) “real-world” clinical trial experience to support the safety, efficacy and durability of its use across a broad spectrum of patient and lesion types

– Unmatched compliance in 4-year follow-up of pivotal RCTs (94% to 98% in CYPHER® Stent vs. BMS RCTs through ≥4 years)

– Longest duration of follow-up (5 years) of any DES program

• Individual randomized, clinical trials (RCTs) and systematic overview of RCTs support the efficacy benefit and comparable safety of CYPHER® Stent vs. BMS, vs. other DES

– Cordis presentations of meta-analyses are limited to the highest level of evidence (i.e., ACC/AHA/ESC Level 1A Evidence)

• Extensive evaluation in broad range of patients further shows consistency in efficacy and safety results

The CYPHERThe CYPHER®® Stent is indicated for Stent is indicated for de novode novo lesions of length lesions of length ≤≤ 30 mm in native coronary arteries with a RVD 30 mm in native coronary arteries with a RVD ≥≥ 2.5 to 2.5 to ≤≤ 3.5 mm3.5 mm

4

TVF (%)

MACE (%)

TVR (%)

TLR (%)

Event

14.112.1

13.312.1

14.712.3

14.912.5

Control-Sirolimus@ 5 yrs

Control-Sirolimus@ 9 mos

SIRIUS – Changes in Clinical Events (Control-Sirolimus) @ 9 mos and 5 yrs

∆∆

∆∆

∆∆

∆∆

∆∆

∆∆

∆∆

∆∆

For all clinical endpoints, there is an increase For all clinical endpoints, there is an increase in the difference between control and sirolimus in the difference between control and sirolimus

event rates from 9 mos to 5 yrs! event rates from 9 mos to 5 yrs! Leon et al. ACC 2007

55 Pooled E-SIRIUS, C-SIRIUS, SIRIUS, RAVEL TrialsCumulative Incidence of Stent Thrombosis to Latest Follow-up (4-5 Years, 4 Trials)

SESSES1.2%1.2%

BMSBMS0.6%0.6%

pp--ValueValue0.2160.216

Data between 4 and 5 years and beyond are from the RAVEL and SIRData between 4 and 5 years and beyond are from the RAVEL and SIRIUS TrialsIUS Trials

ProtocolProtocol

BMSBMSSESSES

SESSES1.7%1.7%

BMSBMS1.9%1.9%


SESSES4.1%4.1%

BMSBMS5.1%5.1%


Definite or Definite or Probable ARCProbable ARC

Any ARCAny ARC

SESSES1.4%1.4%

BMSBMS1.0%1.0%


Definite ARCDefinite ARC

••These studies were not individually or collectively powered to aThese studies were not individually or collectively powered to assess differences in the rates of rare events, such as stent thrssess differences in the rates of rare events, such as stent thrombosisombosis

6

Dedicated Trials with CYPHER® Stent in Specific Patient/Lesion Types

Single, De Novo

LongLesions

SmallVessels

DM

MVD

ISR

CTO

Bifurcations

AMI

LeftMain

DirectStenting

Stairway to Evidence-Based Medicine

RAVEL, SIRIUS, REALITY, ENDEAVOR III

DIRECT

TYPHOONSTRATEGYSESAMIMISSIONPROSIT

Park LLPark LL 2

SVELTE,SIRIUS 2.25SES-SMARTPache, et al.ISAR-SMART 3

PORTO IDECODESCORPIUSDIABETES, CARDIA*ISAR-DIABETES

ACROSS*PRISON II

TROPICALSISRRIBS IIISAR-DESIRE

ARTS-2

PRE-COMBAT*

SIRIUS-BIFNordic PCI

Differing Complexity

* Trials have not been presented/published

Randomized Controlled Trial (RCT) vs. BMS, Brachytherapy, or POBAProspective NON-RCTs RCTs VS. DES

SIRTAX, BASKET, and TAXi (All-Comers), Z

hang, et al.

E-SIRIUS,

C-SIRIUS

SCANDSTENT, CORPAL, Cervinka, et al. (high-ris

k)SVG

RRISC

17 RCTs:SES vs. BMS

N=5,602

13 RCTs SES vs. PES

n = 7,917

7

7

0.0%

0.2%

0.4%

0.6%

0.8%

1.0%

0 180 360 540 720

ARC Definite / ProbableARC Definite / Probable

30 Days 6 Mos. 1 Yr. 1.5 Yrs. 2 Yrs 30 Days 6 Mos. 1 Yr. 1.5 Yrs. 2 Yrs n of pts 0.36% 0.55% 0.62% 0.73% 0.73%n of pts 0.36% 0.55% 0.62% 0.73% 0.73%at risk 6816 6483 6057 5561 1745 1264at risk 6816 6483 6057 5561 1745 1264

FollowFollow--up interval ( Days)up interval ( Days)Slide used with permission from Dr. Takeshi Kimura

Stent Thrombosis in the JStent Thrombosis in the J--CYPHER RegistryCYPHER Registry

Cum

ulat

ive

Inci

denc

e R

ate(

%)

Cum

ulat

ive

Inci

denc

e R

ate(

%)

8

Type of Stent Thrombosis (KType of Stent Thrombosis (K--M)M)

MATRIX Registry

0.1

0.3

0.30.7

0.3 0.3

0.4

0.3

0.0

0.5

1.0

1.5

30 days 6 months 1 year 2 year

Definite Probable

0.4 %0.6 % 0.6 %

1.1 %

%

n=9 n=12

Dangas ACC 2007

9

Risk RatioRisk Ratio(95% CI)(95% CI) % Weight% Weight

TAXiTAXi 2.94 ( 0.31, 27.80)2.94 ( 0.31, 27.80) 1.0 1.0 ISARISAR--DESIREDESIRE 0.42 ( 0.19, 0.92)0.42 ( 0.19, 0.92) 7.3 7.3 ISARISAR--DIABETESDIABETES 0.53 ( 0.23, 1.21)0.53 ( 0.23, 1.21) 6.6 6.6 SIRTAXSIRTAX 0.55 ( 0.36, 0.86)0.55 ( 0.36, 0.86) 18.3 18.3 CORPALCORPAL 0.64 ( 0.36, 1.11)0.64 ( 0.36, 1.11) 12.7 12.7 REALITYREALITY 0.96 ( 0.64, 1.44)0.96 ( 0.64, 1.44) 20.0 20.0 BASKETBASKET 0.50 ( 0.22, 1.14)0.50 ( 0.22, 1.14) 6.6 6.6 ISARISAR--SMART 3SMART 3 0.43 ( 0.23, 0.80)0.43 ( 0.23, 0.80) 10.8 10.8 Zhang et alZhang et al 0.73 ( 0.36, 1.45)0.73 ( 0.36, 1.45) 9.0 9.0 Long DES IILong DES II 0.32 ( 0.12, 0.86)0.32 ( 0.12, 0.86) 4.8 4.8 PROSITPROSIT 0.33 ( 0.09, 1.19)0.33 ( 0.09, 1.19) 2.9 2.9 OverallOverall 0.59 ( 0.47, 0.74)0.59 ( 0.47, 0.74),, II22=16.1%=16.1%

0.040.04 0.10.1 0.50.5 11 22 1010 2525

Risk RatioRisk RatioFavours SESFavours SES Favours PESFavours PES

SIRPACT MetaSIRPACT Meta--analysis of CYPHER vs. Taxus RCTsanalysis of CYPHER vs. Taxus RCTsSignificantly Lower TLR with CYPHERSignificantly Lower TLR with CYPHER

WindeckerWindecker S., et al., TCT 2005; Poster Presentation.S., et al., TCT 2005; Poster Presentation.

1010

Source: A. Kastrati, FDA Panel Presentation, Washington, DC, December 2006

Kastrati, et al., MetaKastrati, et al., Meta--analysis of the CYPHERanalysis of the CYPHER®® Stent vs. the Stent vs. the Taxus Stent RCTsTaxus Stent RCTsSignificantly Lower MACE with the CYPHERSignificantly Lower MACE with the CYPHER®® StentStent

N=5,074. Mean follow-up 25.1 months

FDA has not made any determination as to the safety & efficacy of the CYPHER® Stent in people with diabetes, ISR, small vessels, long lesions

1111

A. Kastrati, FDA Panel Presentation, Washington, DC, December 2006N=5,074. Mean follow-up 25.1 months

Kastrati, et al., MetaKastrati, et al., Meta--analysis of the Cypheranalysis of the Cypher®® Stent vs. the Stent vs. the Taxus Stent RCTsTaxus Stent RCTs

FDA has not made any determination as to the safety & efficacy of the CYPHER® Stent in people with diabetes, ISR, small vessels, long lesions

1414

Rotterdam ExperienceRotterdam ExperienceAdjusted 3Adjusted 3--year Survivalyear Survival

0 1y 2y 3y

90

92

94

96

98

100

Bare metalCypher® StentTaxus

97.4%

95.5%95.8%

Log rank p-valuesSES vs. BMS p=0.033SES vs. PES p=0.010PES vs. BMS p=0.52

2514844222730

2488840221190Group 0

BMS 2428SES 866PES 2835 2514

844222730

2488840221190Group 0

BMS 2428SES 866PES 2835

DaemenDaemen, , SerruysSerruys et al. Personal Communicationet al. Personal Communication

"Registry data alone do not provide a reliable basis for direct comparison among treatments. These registry data should be considered in conjunction with existing data from other registries and randomized controlled trials."

15

Unadjusted Cumulative Incidence of Death and MI (Single Stent)

Adapted from: Lagerqvist B., Wallentin L., FDA Panel Hearing, Dec 7 2006.

1616

SCAAR (Death/MI: One Stent)SCAAR (Death/MI: One Stent)Swedish Coronary Angiography and Angioplasty RegistrySwedish Coronary Angiography and Angioplasty Registry

Source: L. Wallentin, FDA Panel Presentation, Washington, DC, December 2006

* adjustment for baseline differences does not affect the trends: dotted vs. solid lines"Registry data alone do not provide a reliable basis for direct comparison among treatments. These registry data should be considered in conjunction with existing data from other registries and randomized controlled trials."

17

ARTS II - Death/CVA/MIs up to 3 years

Time (Months)

Sur

viva

l (%

)

1009590858075706560

- ARTS II

- ARTS I CABG

- ARTS I PCI

0 6 12 18 24 30 36

92.0%89.1%87.2%

P (log rank) =0.07 between ARTS II and ARTS I-CABG

P (log rank) =0.004 between ARTS II and ARTS I-PCI

Serruys et al. ACC 2007

Cordis and Conor Clinical Trials ProgramInnovate, Inform, Adapt

√√√OUSFIH C-Sirolimus

√√√US/OUSSIRIUS, 10 RCT, MATRIX Trial Extension

√*

√*

√

APT

EfficacySafetyProgram

√√√√OUSSymBio

US/OUS

OUS

US/OUS

US/Japan

OUS

Geography

√√√√√IIE (eg, ACROSS)

√√√√Corio

√√√√CoStar II

√*√√√*ELITE

√√√E-Select

Expanded Indications

LateEarlyLateEarly

*Includes PMS Registries

CYPHER® ELITE™ Stent

•CYPHER® Elite™Stent will feature a new stent design and advanced SDS

SDS

Stent Design

Stent Material

Drug

• Highly Deliverable Sonic SDS

– New design and technologies– Optimized for deliverability and

profile from tip through hub

• Redesigned Platform – New level of flexibility and conformability– Designed for uniform coverage at every

vessel size

• Stainless Steel– High Strength– Long record of Biocompatibility

• Proven Drug and Release Kinetics– Safe, effective Sirolimus – Moderate release profile

ELITE

~1750 Patients≤2 Vessel De novo Coronary Lesions ≥ 2.25mm to ≤ 4.0mm, Length ≤ 55 mm2:1 Randomization, Single Blind~70 Centers in United StatesTwo component, parallel approach

~1750 Patients≤2 Vessel De novo Coronary Lesions ≥ 2.25mm to ≤ 4.0mm, Length ≤ 55 mm2:1 Randomization, Single Blind~70 Centers in United StatesTwo component, parallel approach

Primary Endpoint: 12 month Target Vessel and Lesion Failure (cardiac death, target vessel MI, ischemia driven TLR)

Angio/IVUS: 12 month Angiography (300 pts); IVUS (120 pts)

Primary Endpoint: 12 month Target Vessel and Lesion Failure (cardiac death, target vessel MI, ischemia driven TLR)

Angio/IVUS: 12 month Angiography (300 pts); IVUS (120 pts)

Randomization GroupRandomization Group Annual (thru 5y): Cardiac death, target vessel/all MI, TLR, TVR, APT compliance/risk

Annual (thru 5y): Cardiac death, target vessel/all MI, TLR, TVR, APT compliance/risk

Parallel ELITE/ CYPHER Registries

Parallel ELITE/ CYPHER Registries



Expanded Indications: Diabetes, Direct stenting, Long lesions (≥40 mm), ≤2 Vessel, ACSExpanded Indications: Diabetes, Direct stenting, Long lesions (≥40 mm), ≤2 Vessel, ACS

Advanced DES Programs

A Stent Specifically Designed for Controlled Drug Delivery from a Bioresorbable Polymer

Bioresorbable Polymer

Reservoir Technology

Cobalt Chromium

1,675 Pts Randomized 3:2 CoStar: TaxusSingle De Novo Native Coronary Artery Lesions, ≤2 VesselsReference Vessel Diameter: 2.5 - 3.5 mmLesion Length: ≤30 mm79% (1,330) Single Vessel – 21% (345) Multi-Vessel71 Sites in USA, Europe, and New Zealand

1,675 Pts Randomized 3:2 CoStar: TaxusSingle De Novo Native Coronary Artery Lesions, ≤2 VesselsReference Vessel Diameter: 2.5 - 3.5 mmLesion Length: ≤30 mm79% (1,330) Single Vessel – 21% (345) Multi-Vessel71 Sites in USA, Europe, and New Zealand

Primary Endpoint: 8 month MACESub-Studies: QCA N=(350); IVUS (N=70);

pK (N=45)Dual antiplatelet therapy for 6 mos

Primary Endpoint: 8 month MACESub-Studies: QCA N=(350); IVUS (N=70);

pK (N=45)Dual antiplatelet therapy for 6 mos

989 CoStar686 Taxus989 CoStar686 Taxus



PMS RegistryPMS Registry Annual (thru 5y): Cardiac death, target vessel/all MI, TLR, TVR, APT compliance/risk


COSTAR II TrialProspective, Randomized, Single-Blind, Non-Inferiority


Conor SirolimusBioresorbable PLGA polymer/SirolimusTimeline: 2007/2008

Conor SirolimusBioresorbable PLGA polymer/SirolimusTimeline: 2007/2008

Specifically Designed for Controlled Drug Delivery from a


Specifically Designed for Controlled Drug Delivery from a



Conor AMI, Diabetes, Heart Failure…Bioresorbable PLGA polymerMural sustained release of Sirolimus, Pro-healing therapies or otherLuminal burst release of Adenosine or other Reperfusion Injury drug

Conor AMI, Diabetes, Heart Failure…Bioresorbable PLGA polymerMural sustained release of Sirolimus, Pro-healing therapies or otherLuminal burst release of Adenosine or other Reperfusion Injury drug

25Driving Innovation and Advancing Patient Care:Driving Innovation and Advancing Patient Care:Cordis PipelineCordis Pipeline

201020102009200920082008

REGATTAREGATTA™™GuidewiresGuidewiresWorkhorse, Workhorse,

SB, HSSB, HSEnsureEnsure

Closure Closure Device*Device*

FIRE STARFIRE STAR™™PTCA PTCA

Balloon Balloon Catheter*Catheter*

TransradialTransradialAccessAccess

Kit*Kit*

CoStarCoStar®®**StentStent

CYPHERCYPHER®®ELITEELITE™™**

StentStent

NEXTNEXTGENGEN

STENTSTENT

DURA STARDURA STAR™™PTCAPTCA

BalloonBalloonCatheter*Catheter*

20072007

* Products under development and are not approved or available for sale or use in US.* The CoStar Stent is a product of Conor Medsystems, LLC

The third-party trademarks used herein are trademarks of their respective owners.

Future Iterations(Development Underway)

26

Driving Innovation and Advancing Patient Care

Platform Technologies: treating the patients of tomorrowPlatform Technologies: treating the patients of tomorrow

BiologicsDeveloped as an

incubator, Biologics Delivery System (BDS) is

focused on leveraging NOGA

mapping and catheter injection

technologies

Structural Heart Defects

Focusing on solutions to close PFOs and repair and replace heart

valves

Vulnerable Plaque

Developing a drug/device solution to

stabilize those plaques that

rupture and lead to heart attacks

These products under development and are not approved or available for sale or use in US.

27

Sirolimus Reduces Athero Progression in ApoE-/- Mice

*: P< 0.0001 One-way ANONA analysis.

SIR 0 mg/kg (n=10)SIR 0.5 mg/kg (n=6)SIR 1.0 mg/kg (n=8)SIR 4.0 mg/kg (n=8)

0

5

10

15

***

Ath

ero

lesi

on %

Control 0.5 1.0 4.0 mg/kg

28

New Entities Within CordisNew Entities Within CordisPartnering With and Enabling Interventional Cardiologists

Established as a center for

innovation to develop next generation

technology by partnering with physicians to

challenge today’s technology standards.

Established to provide clinical

resources to improve the training and procedural expertise of

physicians and health care providers

worldwide.

Conor Medsystems is the developer of next generation DES

and platform technologies that will provide new opportunities for cardiovascular

care and beyond.* Conor Medsystems,LLC is a part of the Johnson & Johnson Family of Companies and a separate legal entity within the company's cardiovascular franchise.

29

Cordis Clinical and Advanced Technology ProgramsLeveraging Expertise in Interventional Cardiology

• Clinical decision making regarding DES has become increasingly more reliant on availability of long-term outcomes data

• The CYPHER stent has demonstrated clinically meaningful, sustained benefit in reducing the need for repeat revascularizations in a wide array of clinical settings and lesion complexities

• Emerging evidence of differences in safety and efficacy between DES disprove notion of class effect

• Evolution of new DES technologies should ensure further improvement in patient safety and outcomes with potential for patient and lesion-specific DES (reservoir technology)

• Combination of new growth platforms, best in class product portfolio and developmental programs within Cordis intended to enable IC with most broadly based portfolio of cardiovascular solutions

current and future perspectives from cordis cardiology ... · current and future perspectives...

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