Klinikum Rosenheim Department of Diagnostic and Interventional Radiology

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Gunnar Tepe

PTA

Approaches to reduce restenosis

Local Drug Delivery Basic Principles

Stent based

Short time contact

To be modified

Stent design (homogenoius delivery) Delivery kinetic „Coating/Adsorption“ Drug

Mode of delivery (with a balloon, fluid) Adjuncts Drug

Limitations of current techniques in the SFA: High restenosis rate

(better with stents, but still high)

Clinical goal (in Rutherford up to 3) 1. Increase of walking distance

2. Less TLR

Based on long-term patency

SFA

Short time local drug contact:

…the alternative

approach

Failure:

Some DCBs Work, others Do NOT Data from prospective randomized trials

7

TLR at 2 years

Indication Study Formulation DCB POB

A TAXUS Coronary ISR

Paccocath ISR I & II1,2 Paclitaxel + Iopromide

4% 37% PEPCAD II3* 6% 15%

SFA THUNDER4 15% 52% FemPac5 13% 50%

TLR at 9 months

Indication Study Study Flaw DCB TAXUS CYPHER

Small Vessel CAD Piccoleto6* Paclitaxel Alone 32% 10%

DeNovo CAD PEPCAD III7 DCB w/Pre-crimped stent

vs DES 11% 5%

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Success:

Each DEB is different

8

Contresy by Mc Fadden

Device 1

Device 2

Device 3

Same Drug, Different Additives

DCB Companies and Products

DEB Brand

IN.PACT balloons

SeQuent Please Cotavance Pantera Lux

DIOR II

Elutax Lutonix

CE CE CE - CE CE -

Manu-facturer

Medtronic-Invatec B.Braun Bayer-

Medrad Biotronik Eurocor Aachen-Resonance Lutonix

Coating Name FreePac No name No name No name No name No name No name

Drug Paclitaxel Paclitaxel Paclitaxel Paclitaxel Paclitaxel Paclitaxel Paclitaxel

Drug Carrier (Type)

Urea (Molecule

Spacer)

Iopromide (Contrast

Media)

Ultravist 370 (Contrast

Media)

BTHC (Contrast

Media Analog)

Shellac (Resin) None Unknown

Randomized data

DCB companies and products

0.035” System 0.018” 0.014” COOK Advance 18PTX

Medrad Cotavance in development

Eurocor Freeway 35 Freeway 14 (CE)

Aachen Resonance Elutax*

Lutonix Moxy

Cardionovum LegFlow

Caliber Therapeutics TADD

Biotronik Passeo 18 Lux

Medtronic Invatec IN.PACT Admiral IN.PACT Pacific IN.PACT Amphirion

Study types

1.! Proof that the DEB is safe and effective (DEB vs bare balloon)

2.! New indications a) SFA - In stent restenosis b) SFA - With stents c) SFA - with atherectomy d) BTK e) AV-Fistula

Paccocath – Cotavance technology (Thunder, FemPac trial)

Lutonix – Levant 1

3.! For US approval (DEB vs bare balloon)

Proof of concept in PVD

Study Status

COOK Advance 18 100 randomized finished+ 50 additional patients (started)

Medrad Thunder, Fempac 2 positive trials, published (n=90+90)

Eurocor Freeride n=240 patients, starting soon

Aachen Resonance unknown

Lutonix Levant I positive (n=100)

Biotronik Biolux trial n= 60 (34/60)

Medtronic Invatec SFA I n=150 (150/150)

THUNDER: OUTCOMES 6 Month Angio POBA (n=48) DCB (n=41) P

Late Lumen Loss , mm 1.7 ± 1.8 0.4 ± 1.2 < 0.001

RVD, mm 4.9 ± 0.6 5.1 ± 0.6 0.05

MLD, mm 2.8 ± 1.9 4.1 ± 1.4 0.001

Binary Restenosis (%) 44 17 0.01

TLR POBA (n=54) DCB (n=48) P

6 Month (%) 37 4 <0.001

12 Month (%) 48 10 <0.001

24 Month (%) 52 15 <0.001

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Therapy with Paccocath and

uncoated balloon

+

Patient treated with Paccocath

56 years old male patient, occlusion 11cm diabetic, smoker, hypertension, hypercholesterolemia,

Rutherford class 4

Intervention August, 2004 2 paclitaxel-coated balloons; 5 x 100 mm and 4 x 40 mm

March, 2005

March, 2006

Subgroup n, control/ n, DCB

LLL (mm) Control minus

DCB

LLL (%) DCB/

Control

Diabetes 21/14 1.2 33 Restenotic lesion 14/12 1.5 21 Calcification 18/16 1.2 25 > 10 cm 5/8 1.3 50 Pop. involvement 13/11 1.5 29

Group n=129

Control

[mm]

Paclitaxel on balloon

[mm]

Control minus paclitaxel on balloon

[mm] Total 1.7±1.8 0.4±1.2 1.3

Thunder: Subgroups

DCB: Large benefit in all subgroups

Late lumen loss (mm of diameter) 6 month post PTA

FemPac: OUTCOMES

6 Month Angio POBA (n=48) DCB (n=41) P

Late Lumen Loss , mm 0.8 0.3 0.031

RVD, mm 5.1 5.2 0.62

MLD, mm 2.7 3.6 0.037

Binary Restenosis (%) 47 19 0.035

TLR POBA (n=54) DCB (n=48) P

6 Months (%) 33 7 0.002

18-24 Months (%) 50 13 0.001

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Levent I Trial

Levent I Trial

Levent I Trial

Lesions Learnt

DEB:

- Many DEBs available, but different - Paccocath and Lutonix with positive data - Several trials under the way - learn more about indications and limitations - clinical endpoints in bigger studies

Limitations of current techniques in the BTK: 1. Technical success rate

(not addressed by drug eltuing technology) 2. High restenosis rate

(also high with bare stents)

Clinical goal (in Rutherford 5 and 6) 1. Wound heeling, prevention of amputation

2. Less TLR (?)

BTK

BTK DES vs. uncoated stents or

POPA DEBS

Destiny Trial

Presented by Bosiers et al. VEITH November 2010

Destiny Trial

Presented by Bosiers et al. VEITH November 2010

In.Pact Amphirion in BTK

Presented by Schmidt et al. LINC January 2011

In.Pact Amphirion in BTK

Presented by Schmidt et al. LINC January 2011

Lesions Learnt

1.! DES (Cypher, Xience V) reduce restenosis and TLR rates

2.! Endovascular therapy reduces the amputation rate

3.! DES until now failed to show an impact on amputation rates

4.! DEBs seem to reduce the RS rate – prospective studies pending

Further indications

Indication Name

COOK - -

Medrad

In-stent RS SFA BTK BTK

Atherectomy (+EV3)

COPA COBANA (0/70) 6 mo DSA Euro Canal US Canal

Definitve AR (0/100) 12 mo LLL

Eurocor + Stent ?In-stent RS BTK?

Freeway (ca. x/260) in discussion

Aachen Resonance ?In-stent RS? -

Lutonix - -

Biotronik - -

Medtronic Invatec In-stent RS SFA

BTK Shunt

FAIR (23/118) 6 mo DUS In Pact Deep (140/357) 12 Mo DSA + clinical Inpact Shunt (0/136) 6 mo LLL

Possible Limitation of DEBs

+ additive therapies +alternative therapies

Thunder and FemPac A luck shot

The issue of calcification

The issue of calcification

Alternative treatment

+ Turbohawk

The issue of calcification

!

!

!

!

!

!

An Ideal Combination Therapy? Atherectomy + DCB

The future of DEBs

!.is great,

But we have to learn much more +

Further studies are mandatory

Race to the US market

Not easy to be quick: FDA reqirements

Race to the US market

Use the Thunder and FemPac Data Indepented US trial planned (River Trial)

Levant II is planned based on Levant I

SFA II is planned using SFA I