Latest Insights from the LEVANT II study and sub-group analysis

Prof. Dr. med. Dierk Scheinert

Division of Interventional Angiology

University-Hospital Leipzig, Germany

Conflicts of Interest

2

Advisory Board /Consultant:

Abbott, Biotronik, Boston Scientific, Cook Medical, Cordis,

CR Bard, Gardia Medical, Medtronic/Covidien,

TriReme Medical, Trivascular, Upstream Peripheral

Technologies

LEVANT 2 Study Design

Extensive Blinding Steps Taken to Reduce Bias

Randomization 30 days 6 months 12 months

Treating

Physician

Not Blinded

LEVANT 2 was designed to ensure blinding of the

evaluating physician and DUS Tech at every phase including 30 days, 6 months, and 12 months

Blinded

•Patient

•Core Labs

•Patient

•Core Labs

•DUS Tech

•Evaluating

physician

•Patient

•Core Labs

•DUS Tech

•Evaluating

physician

•Patient

•Core Labs

•DUS Tech

•Evaluating

physician

LEVANT 2 RCT (N=476) Primary Patency

Full Wall Apposition Showed Increased Primary Patency at 12 Months*

A post-hoc subgroup analysis suggests the full wall apposition of the Lutonix® 035 Drug Coated Balloon (minimum 1.04:1 balloon-to-artery ratio of the treatment device) showed increased primary patency of 79.9% (at 12 months Kaplan Meier, not pre-specified). Primary patency is defined as absence of binary restenosis defined by DUS PSVR ≥2.5 and freedom from Target Lesion Revascularization (TLR). Primary safety by treatment balloon / artery ratio <1 was 85.8% (DCB) and 82.1% (PTA). Primary safety by treatment balloon / artery ratio >1 was 79.3% (DCB) and 75.5% (PTA). Warning: Do not exceed Rated Burst Pressure.

6

LEVANT 2 Full Wall Apposition

Sub Group

≥1 .04: 1 Balloon to Artery Ratio

LEVANT 2 Clinical Trial

Average 0.9:1

Balloon to Artery Ratio

Procedural Techniques for Optimal Drug Delivery

Balloon Transit Time

Balloon Inflation Pressure

Balloon Inflation Time

Final % Diameter Stenosis

Indicators from Levant 2 Data Analysis

Observations from LEVANT 2 suggest 12 month Primary Patency maybe positively influenced by

LEVANT 2 DCB Procedural Variable Analysis

Subgroup

Test DCB

%(n/N)

[95% CI]

Control PTA

%(n/N)

[95% CI]

Difference

% [95% CI] P-value1

Meet 3 criteria: stenosis, pressure,

inflation

78.6% (22/28)

[63.4, 93.8]

53.3% (8/15)

[28.1, 78.6]

25.2%

[-4.2, 54.7]

0.090

Meet all 4 criteria 91.7% (11/12)

[76.0, 100.0]

53.3% (8/15)

[28.1, 78.6]

38.3%

[8.6, 68.0]

0.023

62%

Pressure >

7 ATM

68%

Final

Residual

Stenosis <

20%

74%

Transit time < 30

sec

65%

Inflation time ≥ 120

sec

65%

75%

69%

77%

84% 82% 92%

79%

85%

Post-hoc, sub-group analysis suggests that DCB 12 M Primary Patency may be: Improved with 3 variables Optimal with all 4 variables

n=27

n=28

n=22 n=19 n=12

LEVANT 2 PTA Procedural Variable Analysis

Pressure >

7 ATM

Final

Residual

Stenosis <

20%

Inflation

time ≥ 120

sec

59% Levant 2 sub-group analysis suggests that a similar effect was not observed with PTA

n=29

n=32 n=45

n=15 63% 44%

53%

German Sub-Group Analysis

Angiographic Characteristics German vs. non-German Cohorts

German Non-German

Two Lesions Treated, % (n/N) 1.6% (2/126) 2.6% (9/350)

DeNovo Target Vessel, % (n/N) 88.9% (112/126) 83.7% (293/350)

Number of Patent Run-Off Vessels 1.7 ± 1.2 (126) 2.1 ± 0.9 (350)

Reference Vessel Diameter (RVD), mm 4.8 ± 0.8 (126) 4.8 ± 0.8 (350)

Lesion Length, mm 57.7 ± 41.0 (126) 64.7 ± 40.9 (349)

Treated Length, mm 100.3 ± 45.5 (126) 110.6 ± 48.3 (350)

Total Occlusions, % (n/N) 23.0% (29/126) 20.3% (71/350)

Calcification, % (n/N) 60.3% (76/126) 58.3% (204/350)

Severe Calcification, % (n/N) 11.1% (14/126) 9.1% (32/350)

Most Distal Lesion Location, % (n/N)

Proximal SFA 7.1% (9/126) 9.4% (33/350)

Mid SFA 51.6% (65/126) 48.6% (170/350)

Distal SFA 33.3% (42/126) 32.6% (114/350)

Proximal Popliteal 2.4% (3/126) 5.4% (19/350)

Mid Popliteal 4.8% (6/126) 3.1% (11/350)

Distal Popliteal 0.8% (1/126) 0.9% (3/350)

German Non-German

Contralateral Access, % (n/N) 57.9% (73/126) 79.1% (277/350)

Predilation Performed (All Lesions), % (n/N) 100.0% (126/126) 100.0% (350/350)

Maximum %DS Post-Predilation, Pre-Treatment 41.8 ± 13.0 (121) 40.9 ± 13.1 (347)

Total Paclitaxel on DCB Balloons Used per Subject (mg) 3.2 ± 1.6 (83) 3.7 ± 1.8 (233)

Transit Time 21.8 ± 11.9 (105) 39.5 ± 29.3 (327)

Inflation Time per Balloon (seconds) 129.8 ± 74.3 (157) 167.4 ± 91.7 (455)

Max Pressure of Treatment Balloons (atm) 9.0 ± 2.2 (157) 7.7 ± 2.1 (455)

Treatment Overstretch (inflated diameter/RVD) 0.9 ± 0.2 (106) 0.9 ± 0.2 (333)

Dissections, % (n/N)

Grade A 36.5% (46/126) 38.3% (133/347)

Grade B 31.7% (40/126) 21.3% (74/347)

Grade C 1.6% (2/126) 5.2% (18/347)

Post-dilatation PTA, % (n/N) 17.5% (22/126) 22.3% (78/350)

Provisional Bailout Stenting, % (n/N) 6.3% (8/126) 3.1% (11/350)

Procedural Embolism, % (n/N) 1.6% (2/126) 0.9% (3/350)

Diameter Stenosis (post-procedure), %DS 19.4 ± 10.4 (126) 21.5 ± 9.7 (349)

Procedural Success (All Lesions), % (n/N) 90.5% (114/126) 87.4% (305/349)

Procedural Characteristics German vs. non-German Cohorts

Primary Patency Kaplan Meier

Efficacy,

Primary Patency Lutonix

DCB (N=83)

Standard

PTA (N=43) Difference P-value

@365 days 79.4% 57.8% 21.6% 0.015

Prim

ary

Pate

ncy (

%)

Test DCB Control PTA

Time

days

Survival

%

Events

n

at Risk

n

Survival

%

Events

n

at Risk

n

log

rank P

30 91.5% 7 74 88.1% 5 37 0.574

183 88.9% 9 68 76.2% 10 30 0.076

365 79.4% 16 50 57.8% 17 19 0.015

Freedom from TLR Kaplan Meier

Efficacy,

Primary Patency Lutonix

DCB (N=83)

Standard

PTA (N=43) P-value

@365 days 96.1% 82.0% 0.012

Test DCB Control PTA

Time

days

Survival

%

Events

n

at Risk

n

Survival

%

Events

n

at Risk

n

log

rank P

30 98.8% 1 80 100.0% 0 41 0.480

183 98.8% 1 76 92.6% 3 36 0.080

365 96.1% 3 63 82.0% 7 28 0.012

Global SFA Real-World Registry 12 Month Outcomes

Global SFA Registry Procedural Analysis

20,9

14,6

LEVANT 2 (N=316) Global SFA (N=680)

Final % DS**

7,8

9,7

LEVANT 2 (N=432) Global SFA (N=674)

Balloon Inflation Pressure* (ATM)

** – Maximum % DS Mean ± sd (n) * – Maximum balloon pressure Mean ± sd (n)

Measure Lutonix DCB

% (n/N)

Freedom from TLR 94.3% (595/631)

30 Day Safety 99.7% (677/678)

Lutonix Global SFA Real-World Registry 12 Month Results

Lutonix Global SFA Real-World Registry Sub-group Analysis Long Lesions

(140 – 500 mm)

All Lesions

(23 – 500 mm)

Long Lesions

(140 – 500 mm)

Total Lesion Length (mm) 101.2 ± 84.2 (685) 212.3 ± 65.3 (140)

Treated Length (mm) 136.6 ± 89.7(685) 235.8 ± 74.0 (140)

Calcification, % (n/N) 50.2% (238/474) 57.5% (46/80)

Total Occlusion, % (n/N) 31.2% (214/686) 42.1% (59/140)

Lesion Locations, % (n/N)

SFA, % (n/N) 70% (483/690) 66.4% (93/140)

Proximal Popliteal, % (n/N) 16.8% (116/690) 15.7% (22/140)

Mid & Distal Popliteal, % (n/N) 13.1% (91/690) 17.9% (25/140)

%DS post-treatment, % 14.6 ± 18.7 (680) 19.0 ± 21.0 (140)

Bail-out Stenting, % (n/N) 25.3% (174/689) 35.7% (50/140)

Dissection, % (n/N) 30.1% (135/448) 34.3% (48/140)

Baseline Lesion Characteristics All Lesions vs Long Lesions

(140 – 500 mm)

Measure All Lesions

% (n/N)

Long Lesions

% (n/N)

Freedom from TLR 94.3% (595/631) 93.7% (119/127)

30 Day Safety 99.7% (677/679) 100.0% (138/138)

12 Month Results All Lesions vs Long Lesions

(140 – 500 mm)

Freedom from TLR

Sub-group All Lesions

% (n/N)

Long Lesions

% (n/N)

Calcification 95.9% (213/222) 97.6% (41/42)

CTO 94.8% (184/194) 100.0% (51/51)

12 Month Sub-group Analysis

All Lesions vs Long Lesions (140 – 500 mm)

22

Freedom from TLR

Sub-Group Long Lesions

% (n/N)

Lesions >25cm 94.0% (47/50)

Lesions >25cm - No Bailout Stent 96.0% (24/25)

Lesions >25cm - With Bailout Stent 92.0% (23/25)

12 Month Sub-group Analysis

Long Lesions >25cm

Summary

23

• LEVANT 2 post-hoc sub-group analysis suggests that DCB 12 M Primary Patency maybe influenced by balloon Transit time, Inflation Pressure, Inflation Time and Final % Diameter Stenosis

• LEVANT 2 German cohort suggest that good DCB procedures result in durable long term clinical benefits

• Global SFA Registry showed favorable Freedom from TLR of at 12 months, including in: • females, calcified lesions and CTOs

• Long Lesions (140 – 500 mm)

• Global SFA Regisry interim data suggest sustained benefits at 24 months

Latest Insights from the LEVANT II study and sub-group analysis

Prof. Dr. med. Dierk Scheinert

Division of Interventional Angiology

University-Hospital Leipzig, Germany