Six Month Results of the Global BIOLUX P-III All-Comers Registry using Drug Coated Balloon in Infra-Inguinal Artery Disease

Dr. Shaiful Azmi Yahaya, FNHAM, FAPSIC Institut Jantung Negara, Kuala Lumpur, Malaysia

CCI on behalf of the BIOLUX P-III Investigators

Disclosure

• Speaker name: Dr. Shaiful Azmi Yahaya

I have the following potential conflicts of interest to report:

Consulting

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s)

X I do not have any potential conflict of interest

Passeo-18 Balloon

Catheter

Balloon Platform

Improves ease of handling

Protects the user and balloon from contact and damage

SafeGuard Insertion Aid

Drug: Paclitaxel

Excipient: Butyryl-Trihexyl Citrate (BTHC)

Coating

Passeo-18 Lux combines proven technologies for treating lower limb arteries

Paclitaxel blocks the cell cycle directly

Paclitaxel inhibits the cell cycle directly vs. Limus drugs which act indirectly DCB‘s aim for a high-dose effect of Paclitaxel, causing cell‘s mitotic arrest A low-dose effect is expected to sustain antiproliferation long term

Mode of action for Paclitaxel and Limus drugs

BTHC in the “Lux” formulation allows to balance good coating adhesion to the balloon surface

and rapid drug delivery upon vessel contact

BTHC assures micro-crystalline Paclitaxel structure in “Lux” formulation for optimal tissue

absorption and retention

“Lux” formulation with BTHC is safe and biocompatible

BTHC fulfills the requirements of an ideal excipient for DCB

applications

6

GAP 2015

Passeo-18 Lux Clinical Trial Program

Study Device(s) Indication Design Primary

Endpoint PI(s)

Passeo-18 Lux

vs. Passeo-18 SFA

EU Multicenter FIM RCT

(60 pts/5 sites) LLL @6m D. Scheinert

Passeo-18 Lux

vs. Passeo-18 BTK

EU Multicenter FIM RCT

(72 pts/6 sites)

MAE@1m

PP@6m T. Zeller

Passeo-18 Lux

Infrainguinal

Arteries

Global Multicenter All-

comers

Registry

(min. 700 pts/55 sites)

MAE@6m

FTLR@12m G. Tepe

Passeo-18 Lux

+ Pulsar-18 SFA

EU Multicenter Single-arm

trial (120 pts/5 sites) PP@12m M. Bosiers

Passeo-18 Lux

vs. PTA

AV Fistula

Access

Canadian Multicenter RCT

(120 pts/4 sites) LLL@6m E. Terasse

Passeo-18 Lux

+ Pulsar-18 SFA

Australian Single-arm trial

(100 pts)

PP@12m

PP@24m P. Mwipatayi

Passeo-18 Lux In-stent

restenosis

Australian Retrospective

registries

(35* pts / 29° pts)

PP, FTLR, MAE

@6m

P. Myers*

D. Robertson°

*Investigator-Initiated Trials

*

*

*

*

7

GAP 2015

BIOLUX P-I 6 month Late Lumen Loss Comparison of Peripheral DEB RCTs

References: BIOLUX P-I. Scheinert et al. Presented at EuroPCR 2012 THUNDER Tepe et al: N Engl J Med. 2008 Feb 14;358(7):689-99. FEMPAC Werk et al: Circulation. 2008;118:1358-1365. PACIFIER Werk et al: Circ Cardiovasc Interv. 2012 Dec;5(6):831-40 LEVANT-I: Scheinert et al.: JACC: Cardiovasc Interv. 2014; 7(1): 10-19.

8

GAP 2015

Death Major

Amputation TLR TVR

TL

Thrombosis

DCB (%) 0.0% 0.0% 0.0% 0.0% 0.0%

POBA (%)

[CI] 0.0%

2.8%

[0.4-18.1]

5.6%

[1.4-20.7]

5.6%

[1.4-20.7] 0.0%

p-value - 1.000 0.493 0.493 -

p* < 0.05 significant

BIOLUX P-II: Brodmann M Presented at LINC 2014

Major Adverse Events at 30 days Adjudicated by an Independent Clinical Events Committee

Time to Event (days)

POBA 8.3% [2.8 – 23.7]

DCB 0.0% [0.0 – 0.0] 0%

10%

20%

30%

40%

50%

0 30

MAE (%)

p-value : 0.239 (Fisher‘s exact)

p-value : 0.239 (Fisher‘s Exact)

9

GAP 2015

BIOLUX P-II: Brodmann M Presented at LINC 2014

0.0%

20%

40%

60%

80%

100%

Time to Event (days)

0 30 60 90 120 150 180

POBA 75.9% [61.4 – 85.6]

DEB 82.4% [66.5 – 91.2]

p-value : 0.452 (Log Rank)

TL Primary Patency at 6 months Evaluated by an Independent Core Laboratory

p* < 0.05 significant

Six Month Results of the Global BIOLUX P-III All-Comers Registry using Drug Coated Balloon in Infra-Inguinal Artery Disease

Participating Sites 204 Subjects Reached 6 Month FUP

# Subject enrolled #Subjects enrolled up to

25th Jan 2016

Pr G. Tepe (CCI) RoMed Klinikum Rosenheim Germany 3 36

Pr M. Brodmann Medical University Graz Austria 72 120

Pr T. Zeller Universitäts-Herzzentrum Freiburg - Bad Krozingen Germany 28 84

Dr J. K. Christensen Kolding Hospital Denmark 15 28

Dr L. Spak VUSCH East Slovak Cardiology Institute Slovakia 12 42

Pr C. Binkert Kantonspital Winterthur Switzerland 12 19

Dr H. Schröder Jüdischen Krankenhaus Berlin Germany 11 20

Pr G. Nano, Policlinico San Donato Italy 8 15

Dr M. Araujo Hospital Universitaro Severo Ochoa Spain 7 16

Dr L. Yo Catharina Ziekenhuis Eindhoven Hospital Netherlands 6 13

Dr J. Dahm Herz-und Gefässzentrum Göttingen Germany 5 18

Pr F. Hammer Cliniques Universitaires Saint-Luc Belgium 5 6

Dr S. Houthoofd UZ Leuven Belgium 5 10

Dr M. Lichtenberg Klinikum Arnsberg Germany 3 10

Dr S. Kum Changi General Hospital Singapore 2 4

Pr J.L. Magne Centre Hospitalier Universitaire de Grenoble France 2 7

Dr J.M. Romero Hospital Universitari Santa Creu i Sant Pau Spain 3 8

Dr D. Kretzschmar Universitätsklinikum Jena Germany 2 6

Dr E. Alejandre-Lafont Universitätsklinikum Giessen und Marburg Germany 2 14

Dr D. Henroteaux CHR de la Citadelle de Liège Belgium 1 13

Later initiated sites 0 171

204 660

DESIGN:

Prospective, international, multi-centre, All-Comers registry, with pre-defined subgroups

700+ subjects

PRIMARY ENDPOINTS:

Clinical:

Freedom from MAE1 at 6 months

Performance:

Freedom from CD-TLR2 at 12 months

First 204 subjects enrolled with de novo or restenotic lesions in the

infra-inguinal arteries

24 month Follow-up

12 month Follow-up

6 month Follow-up N= 204

6 month clinical assessments N = 193 Death N= 10 Withdrawals N= 1

All-Comers Design

(1) Major Adverse Event : Composite of freedom from device and procedure related mortality through 30 days, major target limb amputation and clinically driven target lesion revascularization (TLR). MAE are adjudicated by an independent Clinical Events Committee

(2) Clinically driven TLR/TVR is any re-intervention performed for ≥50% diameter stenosis (visual estimate) at the target lesion/vessel after documentation of recurrent clinical symptoms of the patient

Baseline Characteristics

Age, yrs (mean ± SD), [Min; Max] 70.2 ± 10.4 [44.0 ; 94.0]

Male (n, %) 123 (60.3%)

Medical History N= 204 %

Hypertension 176 86.3%

Hyperlipidemia 144 70.6%

Smoking Current Smokers

139 53

68.1% 38.1%

History of PAOD 121 59.3%

Previous PVI /Surgeries 113 55.4%

Diabetes 97 47.5%

Coronary Artery Disease 78 38.2%

Cerebrovascular Disease 50 24.5%

Lesion Characteristics Lesion Characteristics N= 259

Lesion Length, mm (mean ± SD) 74.3 ± 69.9

Reference Vessel Diameter, mm (mean ± SD)

4.7 ± 1.0

Diameter Stenosis (%) 85.8 ± 13.8

De Novo Lesion (n, %) 136 52.5%

Re-Stenosis (n, %) 39 15.1%

In Stent Restenosis (n, %) 32 12.4%

Occlusion (n, %) 52 20.1%

Lesion Locations N = 259 %

Common Femoral 2 0.8

Superficial Femoral Artery 148 57.1

Femoro-Popliteal 8 3.1

Popliteal Artery 59 22.8

Anterior Tibial Artery 14 5.4

Posterior Tibial Artery 3 1.2

Tibioperoneal Trunc 11 4.2

Peroneal Artery 4 1.5

Combination of Infrapopliteal Arteries 3 1.2

Other (Bypass, Illiac) 7 2.7

23.6%

32.4%

32.8%

10.4% 0.8%

Calcification

None

Mild

Moderate

Heavy

Unknown 44.0% 33.2% 12.4% 7.3% 3.1%

TASC Classification TASC A

TASC B

TASC C

TASC D

Unknown

Procedure Details

N= 259 %

Lesion treated with DCB only 213 82.2

(1) Only planned stenting - not bailout stenting

Combination therapy %

DCB + Stent1 30 11.6

DCB + Scoring / Cutting /Rotational Devices 13 5.0

DCB + Scoring / Cutting /Rotational Devices + Stent 3 1.2

Freedom From MAE (adjudicated by an independent CEC)

Free

do

m f

rom

MA

E

Time to events (days)

94.4% SE 0.0163 CI95% [ 90.2, 96.9]

MAE (composite of procedure or device related death within 30 days post index procedure, CD-TLR, Target Limb Major amputation)

11 94.4%

Death 1 99.5%

Clinically Driven Target Lesion Revascularization 8 96.8%

Target Limb Major Amputation 2 99.0%

N= 143

Surv

ival

Estim

ate:

MAE

0.0%

20%

40%

60%

80%

100%

Time to Event (days)

0 30 180

Surv

ival

Estim

ate:

Clin

ical

ly d

riven

TLR

0.0%

20%

40%

60%

80%

100%

Time to Event (days)

0 30 180

Freedom From Clinically Driven Target Lesion Revascularization1

Time to events (days)

Free

do

m f

rom

Clin

ical

ly D

rive

n T

LR

96.8% SE 0.0112 CI95%[ 93.7, 98.4]

N= 186

(1) Any re-intervention performed for ≥ 50% diameter stenosis (visual estimate) at the target lesion after documentation of recurrent clinical symptoms of the patient

Change in Rutherford Classification Baseline vs 6 Month - Paired Data

0

10

20

30

40

50

60

70

80

90

0 1 2 3 4 5 6

Rutherford Class

Baseline

6 Month Follow-Up

p*<0.0001

p*<0.001

p*=0.1172

p*<0.0001

p*<0.0001

p*=0.0209 p*=0.0126

80.0% of all subjects improved significantly in Rutherford Class at 6 months compared to baseline

* P<0.05 significant

No. of Subjects

0

10

20

30

40

50

60

70

80

90

100

No hurt Hurts little bit Hurts little more Hurts even more Hurts whole lot Hurts worst

Baseline

6 Month Follow-Up

P*=0.1282 P*=0.6015

P* <0.0001

P*<0.0001

P*=0.0325

P*<0.05 significant

P*<0.0001

Change in Pain Scale1

Baseline vs 6 Month - Paired Data

80.4% of all subjects improved significantly in Pain Scale at 6 months compared to baseline

No. of Subjects

(1) Wong-Baker FACES Pain Rating Scale

Conclusion

BIOLUX P-III is a real All-Comers Registry evaluating the performance of DCB in daily practice in respect to patient and lesion characteristics and combination therapy

6 Months results of the first 200 subjects present comparable safety and performance results:

96.8 % Freedom from Clinically Driven Target Lesion Revascularization

80.0 % of subjects improved significantly in Rutherford classification (p<0.001)

80.4% subjects experienced significantly less pain at 6 months compared to baseline (p<0.001)

Further subgroup analysis will reveal even more insight in daily routine practice – specifically DCB in combination therapy

Thank You

Six Month Results of the Global BIOLUX P-III All-Comers Registry using Drug Coated Balloon in Infra-Inguinal Artery Disease

Dr. Shaiful Azmi Yahaya, FNHAM, FAPSIC Institut Jantung Negara, Kuala Lumpur, Malaysia

CCI on behalf of the BIOLUX P-III Investigators