Bioabsorbable Scaffolds: The Next Holy Grail?

New Cardiovascular Horizons

New Orleans, LA

June 06, 2013

Lewis B. Schwartz, M.D., F.A.C.S.

Vascular Surgery and Endovascular Therapy

University of Chicago

2

Rationale for the Development of Bioresorbable Vascular Scaffolds

• Limitations of metallic stents

– restenosis

– stent thrombosis

– chronic inflammation

– imaging artifacts

– jailed side branches

– inhibition of positive remodeling (shear stress adaptation)

– prevention of normal physiologic function such as vasomotion

– need for prolonged anti-platelet therapy

– permanent implant complicating repeat intervention

Adapted from Waksman R. Update on bioabsorbable stents: From bench to bedside. J

Interven Cardiol 2006;19:414-421.

3

Igaki-Tamai PLA Stent

Stone GW. The Promise of ABSORB Bioabsorbable Vascular Scaffolds. Cardiovascular Revascularization Technologies; 2013 February 25; Washington.

Hideo Tamai

Bioresorbable Scaffolds – 9-year follow-up

Onuma Y, Garg S, IOkamura T, Ligthart J, Jan van Geuns R, de Feyter PJ, et al. Ten-year follow-up of the IGAKI-TAMAI stent. A

posthumous tribute to the scientific work of Dr. Hideo Tamai. Euroint. 2009;5 (suppl F):F109-F11.

9-YEARS

PRE-PROCEDURE

POST-DILATION

Igaki-Tamai™ – long-term results

Nishio S, Kosuga K, Igaki K, Okada M, Kyo E, Tsuji T, et al. Long-term (>10 years) clinical outcomes of first-in-man biodegradable

poly-l-lactic acid coronary stents: Igaki-Tamai Stents. Circ.

2012;http://circ.ahajournals.org/content/early/2012/04/09/CIRCULATIONAHA.110.000901.

Device Study Drug Lesions n Outcome

Igaki-Tamai

Igaki-Tamai FIM none coronary 5018% restenosis @ 12-months

28% TLR @ 10-years

AMS (Biotronik)

PROGRESS AMS none coronary 63 48% restenosis @ 12-months

BIOSOLVE-I paclitaxel coronary22 10% restenosis @ 6-months

24 in-scaffold LLL 0.52 mm @ 12-months

REVA

RESORB

none coronary

30 67% TLR @ 6-months

RESTORE I 22 2 MACE @6-months

ABSORB (Abbott)

ABSORB

Cohort A

everolimus coronary

30 12% restenosis @ 6-months

ABSORB

Cohort B

45 2.4% restenosis @ 6-months

56 3.5% restenosis @ 12-months

ABSORB

Extend200 0.5% TLR @ 6-months

DESolve (Elixir)

DESolve I novolimus coronary 15 0% restenosis @6-months

Bioresorbable Coronary Scaffolds – Reported Clinical Studies

Scaffold Coating Drug Delivery system

Bioresorbable Bioresorbable Everolimus XIENCE V

• Poly(L-lactide) (PLLA)

• Naturally resorbed,fully metabolized

• Poly(D,L-lactide)

(PDLLA) coating

• Naturally resorbed,

fully metabolized

• Similar dose density and release rate to XIENCE V

• World-class

deliverability

Abbott Vascular Everolimus Eluting

Bioresorbable Vascular Scaffold Components

Photos taken by and on file at Abbott Vascular.

Representative photomicrographs of porcine coronary arteries, 2x

1 month 6 months 1 year 2 years6 months 1 year 2 years 4 years3 years2 years 4 years1 year 2 years 4 years6 months 1 year 2 years 4 years

Photos taken by and on file at Abbott Vascular. Tests performed by and data on file at Abbott Vascular.

Absorb™

Cypher®

Absorb™ v. Cypher®

Virmani R. Challenges for the development of biodegradable scaffolds: Insight from the preclinical trials. Cardiovascular Research Technologies;

2013 February 25; Washington.

BVS Cohort A Degradation on the Bench

and in Porcine Coronary Arteries

A

B

C

DE

A B C D E

Post-procedure

Pre-procedure

A’

B’C’

D’ E’

A’ B’ C’ D’ E’

26 lesions

Pre-procedure

Lesion length (mm) 8.66

RVD (mm) 2.78

MLD (mm) 1.10

DS (%) 59%

Post-procedure

In-stent MLD (mm) 2.33

In-stent DS (%) 16%

In-stent acute gain (mm) 1.24

6-mos. follow-up

In-stent MLD (mm) 1.88

In-stent DS (%) 27%

In-stent late loss (mm) 0.44 ± 0.35

In-stent ABR (%) 11.5%

The Lancet 2008;371:899

CYPHER ENDEAVOR

TAXUS XIENCE V

4 mos 6 mos 8/9 mos 12 mos

Comparison of DES - Late Lumen Loss

0

0.2

0.4

0.6

0.8

1

1.2

1.4

In-s

ten

t la

te lo

ss (

mm

)

ABSORB Cohort ATemporal Lumen Dimensional Changes,

Per Treatment

ABSORBCohort A

Scaffold

Area

11.8%

Post-PCI 6 Mos.n = 25

Late Loss = 0.43 mm

MLA = 5.09mm2 3.92mm2

n = 25

Serruys PW, Ormiston JA, Onuma Y, Regar E, Gonzalo N, Garcia-Garcia HM, et al. A bioabsorbable everolimus-eluting coronary stent

system (ABSORB): 2-year outcomes and results from multiple imaging methods. The Lancet 2009;373:897-910.

• Lower MCUSA (maximum

unsupported scaffold area)

• More even support of arterial

wall

• More uniform strut distribution

• Lower late stent area loss

• Improved stent retention

• Unchanged material and strut

thickness

Onuma Y, Piazza N, Ormison JA, Serruys PW. Everolimus-eluting bioarbsorbable stent - Abbott Vascular programme. Euroint

2009;5(suppl F):F98-F102. 009;373:897-910.

Gomez-Lara J, Brugaletta S, Diletti R, Garg S, Onuma Y, Gogas BD, et al. A comparative assessment by optical coherence tomography

of the performance of the first and second generation of the everolimus-eluting bioresorbable vascular scaffolds. Eur Heart J 2010.

ABSORB Cohorts A & B

Radial Strength

Oberhauser JP, Hosseiny S, Rapoza RJ. Design principles and performance of bioresorbable polymeric coronary scaffolds. EuroInt.

2009;5 (suppl F):F15-F22.

Gomez-Lara J, Brugaletta S, Diletti R, Garg S, Onuma Y, Gogas BD, et al. A comparative assessment by optical coherence tomography

of the performance of the first and second generation of the everolimus-eluting bioresorbable vascular scaffolds. Eur Heart J 2010.

COHORT A COHORT B

ABSORB Cohorts A & B

Post-procedure

6-mos. Post-procedure

6-mos.

Cumulative Incidence Curve for Late Loss

■ BVS Cohort A (N = 26)

■ BVS Cohort B (N = 42)

▲ Xience EES* (N = 23)

Vision BMS* (N = 27)

*SPIRIT First

0.85 ± 0.36 mm0.10 ± 0.23 mm

Serruys PW, Onuma Y, Ormiston JA, de Bruyne B, Regar E, Dudek D, et al. Evaluation of the second generation of a bioresorbable

everolimus drug-eluting vascular scaffold for treatment of de novo coronary artery stenosis: Six-month clinical and imaging outcomes.

Circ. 2010;122(22):2301-12. ABSORB is neither approved nor available for sale in the U.S.

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

-0.5 0 0.5 1 1.5 2

In-Stent Late-Loss (mm)

% P

ati

en

ts

0.19 ± 0.18 mm

0.43 ± 0.37 mm

ABSORB Cohort B: 6-Month QCA – Intent to Treat

ABSORB Cohort B – two-year results

Pre-

Absorb

Immediately

Post Absorb 6 Months 2 Years

Ormiston J, Serruys PW. ABSORB Cohort B Trial – Two year clinical and angiographic results of the ABSORB everolimus eluting bioresorbable

vascular scaffold (poster). Transcatheter Cardiovascular Therapeutics; 2011 November 8; San Francisco, CA.

Byrne RA, Iijima R, Mehilli J, Pinieck S, Bruskina O, Schömig A, et al. Durability of antirestenotic efficacy in drug-eluting stents with and without permanent polymer. J

Am Coll Cardiol: Cardiovasc Interv. 2009;2:291-9.

Byrne RA, Kufner S, Tiroch K, Massberg S, Laugwitz K-L, Birkmeier A, et al. Randomised trial of three rapamycin-eluting stents with different coating strategies for the

reduction of coronary restenosis (ISAR-TEST-3): 2-year follow-up results. Heart. 2009;95:1489-94.

Park KW, Kim C-H, Lee H-Y, Kang H-J, Koo B-K, Oh B-H, et al. Does “late catch-up” exist in drug-eluting stents: Insights from a serial quantitative coronary

angiography analysis of sirolimus versus paclitaxel-eluting stents. Am Heart J. 2010;159:446-53.

Ormiston J, Serruys PW. ABSORB Cohort B Trial – Two year clinical and angiographic results of the ABSORB everolimus eluting bioresorbable vascular scaffold

(poster). Transcatheter Cardiovascular Therapeutics; 2011 November 8; San Francisco, CA.

Byrne RA, Kastrati A, Tiroch K, Massberg S, Wieczorek A, Laugwitz K-L, et al. Two-year outcomes after everolimus- or sirolimus-eluting stents in patients with coronary

artery disease in the ISAR-TEST 4 Trial. Transcatheter Cardiovascular Therapeutics; 2010; San Francisco, California.

Angiographic late lumen loss – two-year results

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

Taxus

(Park)

Taxus

(ISAR-

TEST 2)

Cypher

(Park)

Cypher

(ISAR-

TEST 2)

Cypher

(ISAR-

TEST 4)

Cypher

(ISAR-

TEST-3)

Xience

(ISAR

TEST 4)

Absorb

(Cohort B)

In-s

ten

t o

r scaff

old

LL

L (

mm

)

7.9%

8.5%

758-day HR0.97 [0.42,2.21]

p=0.9379

MA

CE

(C

- De

ath

, M

I, I

D-T

LR

)

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

22%

Time Post Index Procedure (Months)

7.9%

8.5%

758-day HR0.97 [0.42,2.21]

p=0.9379

ABSORB™ BVS(B1+B2)

XV®(3.0 x 18mm subgroup, SPI+SPII+SPIII RCT)

MA

CE

(C

- De

ath

, M

I, I

D-T

LR

)

Rapoza R. Absorb BVS Program: Long-term experimental data angiography, IVUS, OCT, histology and micro CT. Local Drug Delivery and

Cardiovascular Course on Revascularisation; 2012 February 4; Geneva, Switzerland. ABSORB and XIENCE V are trademarks of the Abbott Group of

Companies

Days 0 37 194 284 393 573 758

Absorb™ 101 99 96 96 93 91 41

XIENCE V® 227 224 219 211 204 202 191

Absorb™ v. XIENCE V® at 2-years

0 6 12 18 24

Minimal LD 1.58 mm

Mean LD 2.12 mm

MLD 2.46 mmMean LD 2.72mm

Mean LD∆-0.60mm(-22%)

Minimal LD 2.32 mm

Mean LD 2.67 mm

Mean LD∆+0.55mm(+26%)

Preprocedure

FUP before vasomotion 5 Min. After Methergine After Nitro

Post procedure

QCA post procedure

MLD 2.45mm

Late Loss: -0.01mm

Recovery of Vasoreactivity after Absorb Implantation

Simonton C. The Abbott Vascular DES Pipeline. Cardiovascular Research Technologies; 2013 February 25; Washington. 1.

Adapted from Serruys, PW. ACC 2011. 2. Adapted from Serruys, PW. ACC 2011. 3. Adapted from Serruys, PW, et al. Lancet

2009; 373: 897-910.

in

Ve

sse

l Dia

met

er

(mm

)

Methergine

Acetylcholine

-1

-0.5

0

0.5

1

(n=15)

6 Months1

(n=6) (n=19)

12 Months2

(n=13) (n=9)

24 Months3

(n=7)

Vas

od

ilati

on

Vas

oco

nst

rict

ion

ABSORB Cohort B1 ABSORB Cohort B2 ABSORB Cohort A

(pre

-dru

g in

fusi

on

to

po

st-d

rug

infu

sio

n)

ABSORB Cohort A: 24-Month Results

Okamura T, Serruys PW,

Regar E. The fate of

bioresorbable struts located

at a side branch ostium:

serial three-dimensional

optical coherence

tomography assessment.

Euroint. 2010;

doi:10.1093/eurheartj/ehq175;

online publish-ahead-of-print

31 May 2010.

ABSORB Cohort B - Late Lumen Enlargement by IVUS

Post-PCI 6 Months 2 Years

Lumen Area

6.53 mm26.36 mm2 6.85 mm2

ABSORBCohort B

Serial Analysis

N = 33 N = 33N = 33

Scaffold

Area

↓ 1.7%

Lumen

Area

↑ 7.2%

Late Loss = 0.19 mm

Ormiston J, Serruys PW. ABSORB Cohort B Trial – Two year clinical and angiographic results of the ABSORB everolimus eluting

bioresorbable vascular scaffold (poster). Transcatheter Cardiovascular Therapeutics; 2011 November 8; San Francisco, CA.

ABSORB EXTEND

Non-Randomized, Single-Arm, Continued Access Trial

Simonton C. The Abbott Vascular DES Pipeline. Cardiovascular Research Technologies; 2013 February 25; Washington.

Study Objective Continued Access trial. FPI: Jan 11, 2010

Endpoints Typical PCI clinical endpoints

TreatmentUp to 2 de novo lesions in different epicardial vesselsPlanned overlapping allowed in lesions >22 and ≤ 28 mm

Device SizesScaffold diameters: 2.5, 3.0, 3.5 mmScaffold lengths: 12*, 18, 28 mm

Follow-up (months)

~1,000 subjectsUp to 100 global sites (non-US)

MSCT follow up (n=100)

OCT, IVUS follow up (n=50)

24126 18 36

Bartorelli, A, An Interim Report on the 12-Month Clinical Outcomes from the First 250 Patients Registered, and An Interim Report on the 6-Month Clinical Outcomes from the First 500 Patients Registered, TCT 2012

Clinical Follow-Up

ABSORB EXTEND

Non-Randomized, Single-Arm, Continued Access Trial

Simonton C. The Abbott Vascular DES Pipeline. Cardiovascular Research Technologies; 2013 February 25; Washington.

Bartorelli, A, An Interim Report on the 12-Month Clinical Outcomes from the First 250 Patients Registered, and An Interim Report on the 6-Month Clinical Outcomes from the First 500 Patients Registered, TCT 2012

Intent to Treat (ITT) Analysis – Interim Snapshot

The ABSORB Clinical Trials

Simonton C. The Abbott Vascular DES Pipeline. Cardiovascular Research Technologies; 2013 February 25; Washington.

2011 2012 2013 2014 2015 2016

Total Absorb Pts Studied n=~599 n~965 n~5,709 n~13,463 n~13,463 n~13,463

ABSORB III n = ~1,502

Enrollment & Follow-Up

ABSORB Japan n = ~265

Enrollment & Follow-Up 2 Y1 Y

ABSORB China n = ~200

Enrollment & Follow-Up 2 Y1 Y

ABSORB IIn = ~330

2 Y 3 Y1 YEnrollment & Follow-Up

ABSORB FIRST n = 10,000

Enrollment & Follow-Up

ABSORB PHYSIOLOGY n = ~35

2 Y1 YEnrollment & Follow-Up

ABSORB Extend n = up to 1,000

2 Y 3 Y1 YEnrollment & Follow-Up

ABSORB Cohort B n = 101; FIM

1 Y 2 Y 3 Y 4 Y 5 Y

ABSORB Cohort A n = 30; FIM

5 Y

2 Y1 Y

2 Y1 Y 3 Y

BVS Implantation Technique

• Use online QCA

• Avoid under sizing, as postdilation is limited to 0.5 mm

• Proper lesion preparation = sufficient large balloon

(min 2.5 mm)

• Use more supportive wires

• Direct stenting possible in ACS

Van Geuns R-J. BVS Expand: First results of wide clinical applications. Cardiovascular Research Technologies; 2013

February 25; Washington.

Device Company Study Drug Lesions n Status

DREAMS AMSBiotronik BIOSOLVE I paclitaxel coronary 56

in-scaffold LLL

0.52 mm @

12-months

ReZOLVE

Reva Medical, Inc.

RESTORE I none

coronary

222 MACE @6-

months

RESTORE II sirolimus 125 enrolling

ABSORB

Abbott

ABSORB

EXTEND

everolimus coronary

1000 enrolling

ABSORB III 2000 enrolling

DESolve

Elixir Medical

DESolve I

novolimus coronary

16

in-scaffold LLL

0.19 mm @6-

months

DESolve Nx 126 enrolled

Bioresorbable Scaffolds - Ongoing Clinical Studies

The Resorbable Holy Grail

• Restoration of normal

vasomotion, with NO

production

• Restoration of normal shear

stress and cyclic strain

• Restoration of normal vessel

curvature

• Reduced risk of very late

polymer reactions

• Avoidance/resolution of

positive remodeling and stent

malapposition

• Avoidance/resolution of late

strut fractures

Stone GW. The Promise of ABSORB Bioabsorbable Vascular Scaffolds. Cardiovascular Revascularization Technologies; 2013 February 25; Washington.

• Less neoatherosclerosis

• Un-jailing of side-branches

• Plaque regression

• MRI/CT imaging follow-up

• The return of normal vessel architecture