Three-year Results from the IN.PACT Global Study

Koen Deloose, MD

Head Dept Vascular Surgery

AZ Sint Blasius Dendermonde, Belgium

2iD3 Medical – 2019 |

Disclosure slide

I have the following potential conflicts of interest to report:

Consulting: Medtronic, Spectranetics, Biotronik, Abbott, BD/Bard

iVascular, Bentley, Cook, GE Healthcare, Contego medical,

Boston Scientific, Cardionovum, B Braun, Terumo

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s)

I do not have any potential conflict of interest

Speaker name: Koen Deloose, MD

3iD3 Medical – 2019 |

Background

• Numerous prospective randomized trials have reported the superiority of drug-coated balloons (DCB) over percutaneous angioplasty,1-4 however these studies lack representation of a real-world populations in the treatment of femoropopliteal disease.

• While global registries and studies categorize the role of DCBs for femoropopliteal disease treatment in real world populations,5-10 especially today, in the current circumstances, evidence with follow-up longer than 2 years is needed.

1. Tepe G. et al. Circulation. 20152. Laird J. et al. JACC. 20153. Schneider P. et al. Circ-CI. 20184. Rosenfield K. et al. NEJM. 20155. Thieme M. JACC-CI. 2017

6. Schroe H. et al. CCI. 20187. Scheinert D, PCR Paris, France 20158. Tepe G, CX London, UK 20169. Brodmann M, et al. JACC-CI. 201710.Micari A, et al. JACC-CI. 2018

4iD3 Medical – 2019 |

IN.PACT Global StudyOverview

Bilateral disease

Multiple lesions

SFA and Popliteal Artery

TASC A, B, C, D

RCC 2-4

De novo ISR

Long Lesions

CTOs

All-comersReal-world, prospective, multicenter, single

arm independently-adjudicated

femoropopliteal

1.Syntactx Clinical Events Committee, New York, NY, US

2. VasCore DUS Core Lab, Boston, MA, US

3. SynvaCor Angiographic Core Lab, Springfield, IL, US

* Sponsored by Medtronic plc

• 1535 patients enrolled

• 64 sites in EU, Mid-East, Latin America, Asia

• Independent adjudication by

Clinical Events Committee1

• Prospective subset analysis with core lab2,3 reported results (de novo ISR, long lesions ≥15 cm, CTOs ≥5 cm)

• Safety and effectiveness data on 150 mm DCB

Real-world, prospective, multicenter, single arm independently-adjudicated femoropopliteal study*

5iD3 Medical – 2019 |

IN.PACT Global StudyArchitecture

1416 Subjects

de novo ISR

131 Subjects

Long Lesion (≥15 cm)

157 Subjects

CTO

(≥5 cm)

126 Subjects

Clinical Cohort

Pure Imaging Cohorts

150 mm DCB Cohort

119 Subjects

1535 Subjects Enrolled

This presentation includes outcome data on the 1406 ITT

subjects who comprise the IN.PACT Global Clinical Cohort

1416 Subjects

de novo ISR

131 Subjects

Long Lesion (≥15 cm)

157 Subjects

CTO

(≥5 cm)

126 Subjects

Clinical Cohort

Pure Imaging Cohorts

M. Brodmann

JACC CI 2017

D. Scheinert

Circ. CI 2018

Charing Cross 2016

G. Tepe

6iD3 Medical – 2019 |

IN.PACT Global StudyPrimary Endpoints

1. Any re-intervention within the target lesion(s) due to symptoms or drop of ABI of ≥ 20% or > 0.15 when compared to post-index procedure baseline ABI.

Primary Efficacy Endpoint

Freedom from clinically-driven Target Lesion Revascularization1 within 12 months

Primary Safety Endpoint

Freedom from device- and procedure-related death through 30 days, and freedom from target limb major amputation and clinically-driven Target Lesion Revascularization within 12

months

7iD3 Medical – 2019 |

IN.PACT Global StudyKey Eligibility Criteria

Inclusion and exclusion criteria are intended to allow for evaluation of the IN.PACT™ Admiral™ DCB in a complex, real-world patient population

Inclusion Criteria Exclusion Criteria• Rutherford Class 2, 3 and 4• Lesion(s) in SFA and/or Popliteal

artery• Single or multiple stenosis or

occlusions of any lesion length ≥ 2 cm

• De novo or restenotic (including ISR)

• At least one infrapopliteal run-off vessel

• Rutherford Class 5 and 6• Acute or sub-acute thrombus in

the target vessel• Previous bypass surgery to the

target lesion• Failure to successfully cross the

target lesion with a guide wire

8iD3 Medical – 2019 |

IN.PACT Global StudyBaseline Clinical Characteristics

31%

58%

8% 3%

Rutherford Clinical Classification

RCC 2 RCC 3 RCC 4 RCC 5

1. Baseline serum creatinine ≥ 1.5 mg/dl2. ABI for all target limbs treated during the 1st index procedure are included

(can be bilateral)

*Protocol Deviation

*

IPG Baseline Characteristics N=1406 Subjects

Age (Y, Mean ± SD) 68.6 ± 10.1

Male (%) 67.8% (953/1406)

Diabetes (%) 39.9% (560/1402)

Hypertension (%) 83.4% (1169/1401)

Hyperlipidemia (%) 70.5% (960/1362)

Current Smoker (%) 31.8% (447/1406)

Obesity (BMI ≥ 30 kg/m2, %) 20.5% (285/1391)

Coronary Heart Disease (%) 40.5% (540/1332)

Carotid Artery Disease (%) 20.2% (241/1196)

Renal Insufficiency1 (%) 11.2% (136/1217)

Previous Peripheral Revasc (%) 52.4% (737/1406)

Concomitant BTK Disease (%) 45.3% (594/1310)

ABI2 (Mean ± SD) 0.678 ± 0.218

9iD3 Medical – 2019 |

IN.PACT Global Study Lesion Characteristics

1. Severe calcium definition used by study sites and core laboratory is bilateral calcium at the same location (also measured in sections), ≥ half of the total lesion length, ≥180 (both sides of the vessel at the same location). Dattilo, R; J Invasive Cardiol 2014;26(8):355360.

Lesion CharacteristicsN=1406 SubjectsN=1773 Lesions

Lesion Type: % (n)De novoRestenotic (non-stented)In-stent Restenosis

74.4% (1326/1773)7.7% (136/1773)18.0% (320/1773)

Lesion Length (cm ± SD) 12.09 ± 9.54

Total Occlusions % (n) 35.5% (629/1773)

Calcification % (n)Severe1 % (n)

68.7% (1217/1773)10.2% (181/1771)

RVD (mm ± SD) 5.186 ± 0.681

Diameter Stenosis (% ± SD) 88.8% ± 12.3

Dissections:0A-CD-F

56.8% (1006/1772)35.4% (627/1772)7.8% (139/1772)

10iD3 Medical – 2019 |

IN.PACT Global StudyProcedural Characteristics

1. Device success defined as successful delivery, inflation, deflation and retrieval of the intact study balloon device without burst below the RBP.2. Procedure success defined as residual stenosis of ≤ 50% (non-stented subjects) or ≤ 30% (stented subjects).3. Clinical success defined as procedural success without procedural complications (death, major target limb amputation, thrombosis of the target

lesion, or TVR) prior to discharge.

Procedural CharacteristicsN=1406 SubjectsN=1773 Lesions

Device Success1 % (n) 99.4% (2984/3002)

Procedure Success2 % (n) 99.3% (1386/1396)

Clinical Success3 % (n) 98.8% (1379/1396)

Pre-dilatation % (n)Post-dilatation % (n)

78.0% (1097/1406)35.1% (491/1397)

Provisional Stent % (n) 25.3% (353/1397)

11iD3 Medical – 2019 |

IN.PACT Global StudyFreedom from CD-TLR Through 3 Years

1. Clinically-driven TLR adjudicated by an independent Clinical Event Committee, blinded to the assigned treatment based on any re-intervention at the target lesion due to symptoms or drop of ABI of ≥20% or >0.15 when compared to post-procedure baseline ABI.

12iD3 Medical – 2019 |

IN.PACT Global StudyEffectiveness Outcomes

1. Clinically-driven TLR adjudicated by an independent Clinical Event Committee, blinded to the assigned treatment based on any re-intervention at the target lesion due to symptoms or drop of ABI of ≥20% or >0.15 when compared to post-procedure baseline ABI.

2. Any TLR includes clinically-driven and incidental or duplex driven TLR.3. Primary sustained clinical improvement defined as freedom from target limb amputation, freedom from target lesion

revascularization, and upward shift of at least 1 category on Rutherford class.

Additional 3-year Effectiveness OutcomesIN.PACT Global

N= 1406 Subjects

CD-TLR1 (%n) 23.5% (289/1230)

Time to First CD-TLR(Min, Max)

475.5 ± 286.5(1, 1079)

Any TLR2 (%n) 24.0% (295/1230)

Primary Sustained Clinical Improvement3 (%n) 59.3% (601/1013)

13iD3 Medical – 2019 |

IN.PACT Global Study3-Year Safety Outcomes

1. Safety composite endpoint consists of: Freedom from device- and procedure-related death within 30 days, freedom from target limbamputation within 36 months; and freedom from clinically-driven TLR within 36 months.

2. Major Adverse Events (MAE) defined as all-cause death, clinically-driven TVR, major target limb amputation, thrombosis at the target lesion site at 1080 days.

3 Year Safety OutcomesIN.PACT Global

N= 1406 Subjects

Primary Safety Composite1 75.0% (923/1230)

Major Adverse Events2 32.7% (402/1230)

All-cause Death 8.3% (102/1230)

CD-TVR 24.3% (299/1230)

Major Target Limb Amputation 0.8% (10/1230)

Thrombosis 5.8% (71/1230)

14iD3 Medical – 2019 |

Mortality Rates in ContextAll-Cause Death at 3 Years

1. IN.PACT SFA Schneider P, et al. 2017 Circulation - Cardiovasc Interv: 11; e0058912. IN.PACT Global Presented by Tepe G, 2018 CIRSE, Lisbon, Portugal3. MAJESTIC Presented by Muller-Hulsbeck S, 2017 VEITH, New York, USA4. Complete SE SFA MData on file. Medtronic, Inc.5. DURABILITY II Rocha-Singh K, et al. Cather Cardiovasc Interv 2015: 86; 164-170 6. STROLL Bunte, et al. 2018 Catheter Cardiovasc Interv 2018: 00; 1-97. RESILIENT LifeStent IFU. Revised 2/04-16

15iD3 Medical – 2019 |

Summary

• The IN.PACT Global Study remains the largest drug-coated balloon (DCB) study with independent adjudication and an in-clinic follow up requirement for all subjects.

• Results demonstrate durable outcomes of the IN.PACT™ Admiral™

DCB through 3 years (Freedom from CD-TLR = 76.9%).

• All-cause mortality rate at 3 years is in line with rates from other SFA studies. Importantly, all deaths have been adjudicated by an independent CEC and none are device related.

• Three-year real-world data from the IN.PACT Global Study continues to confirm the safety of the IN.PACT™ Admiral™ DCB.

Three-year Results from the IN.PACT Global Study

Koen Deloose, MD

Head Dept Vascular Surgery

AZ Sint Blasius Dendermonde, Belgium