Drug delivery devices for BTK treatment · FMRP 2016 | 1 LINC AP 2016, Hong Kong Drug delivery devices for BTK treatment Koen Deloose , MD Marc Bosiers Koen Deloose Joren Callaert

FMRP 2016 | 1

LINC AP 2016, Hong Kong

Drug delivery devices for BTK treatment

Koen Deloose , MD

Marc Bosiers Koen Deloose Joren Callaert

A.Z. Sint-Blasius, Dendermonde

Patrick Peeters Jürgen Verbist

W. Van den Eynde

OLV Hospital, Aalst

Lieven Maene Roel Beelen

R.Z. Heilig Hart, Tienen

Koen Keirse Bart Joos

Imelda Hospital, Bonheiden

FMRP 2016 |

Disclosure slide

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)

I do not have any potential conflict of interest

2

FMRP 2016 |

BTK vessels are @risk for restenotic cascade

3

FMRP 2016 |

Drug elution is the only solution…

4

•Crush plaque •Stretch artery • De-endothelialization

•Platelet/fibrin deposition

Signaling

cascades

•SMC migration & division •ECM

production •Re-endotheliazation

RESTENOSIS

Antiproliferative Agents

FMRP 2016 |

Drug elution is the only solution

5

Taxol Family Limus Family

Paclitaxel Siro-limus

Evero-limus

Zotaro-limus

Tacro-limus

DES DCB

Cook

Medical Boston

Scientific Stentys

Medtronic

Bard

Biotronik

Spectranetics

Ivascular

Cardionovum

EuroCor

Boston

Scientific

Cook Medical

Cordis Abbott Medtronic Sorin

Biomedica

FMRP 2016 |

DES – BTK in literature…

6

0 5 10 15 20 25 30 35 40 45 50 55 60

100

90

80

70

60

50

40

30

20

10

0

Time (months)

DES-registry

Primary Patency

DES-RCT

31mm 27mm 21mm

Rastan A. et al (2011). European Heart Journal, 32, 2274-2281 ; Bosiers M. et al (2012). Journal of Vascular Surgery, 55, 390-398

Scheinert D. et al (2012). Journal of the American College of Cardiology, 60, 2290

FMRP 2016 | 7

• Prospective, non-randomized, multi-center study

(3 Belgian, 2 German centers) : 70 patients

• Study objective:

To evaluate the immediate and long-term (up to 12 months) outcome of the PROMUS ELEMENT (PLUS) Everolimus-Eluting Coronary Stent System (Boston Scientific) in a corelab controlled prospective way for BTK lesions of max 40mm

PREVENT study


FMRP 2016 | 8


FMRP 2016 |

Baseline 1MFU 6MFU

Freedom from TLR (%) 100 100 96.8

Patients at risk 70 68 59

9

96.8 %

Baseline 1MFU 6MFU

Primary Patency (%) 100 100 95.4


95.4 %

Baseline 1MFU 6MFU

Freedom amputation (%) 100 100 100


100.0 %


FMRP 2016 | 10

• Prospective, non-randomized, multi-center study

(4 Belgian, 3 German, 1 Australian center)

• Study objective:

To evaluate the immediate and long-term (up to 12 months) outcome of the XIENCE PRIME BX Everolimus-Eluting Coronary Stent System (Abbott Vascular) in a corelab controlled prospective way for BTK lesions between 30mm and 100mm

DESTINY 2 study


FMRP 2016 | 11


FMRP 2016 |

75.4 %

12

84.9 %

time baseline 1MFU 6MFU 12MFU

at risk 60 58 50 42

% 100 100 94.5 84.9


at risk 60 57 43 37 % 100 98.3 83.4 75.4

96.6 %


at risk 60 57 52 49

% 100 96.6 96.6 96.6


FMRP 2016 |

PES BTK-70 study

Prospective, non-randomized, multi-center study ( 5 belgian centers)

To evaluate the immediate and long-term (up to 12 months) outcome of the dedicated BTK SX Paclitaxel-Eluting Stentys Stent System (Stentys) in a corelab controlled prospective way for BTK lesions of max 50 mm

13


FMRP 2016 | 14


FMRP 2016 |

time baseline 6MFU 12MFU

at risk 70 55 46 % 100 89.2 79.1

15

79.1 %



at risk 70 54 43

% 100 87.6 72.6

72.6%


at risk 70 62 55

% 100 98.5 98.5

98.5 %

FMRP 2016 | 16 Fusaro M, JACC 2013;6:1284-93


FMRP 2016 | 17


Fusaro M, JACC 2013;6:1284-93

FMRP 2016 | 18


Fusaro M, JACC 2013;6:1284-93

FMRP 2016 | 19

FMRP 2016 | 20

• Coronary DES trials showed increased risk for restenosis if full index lesion is not completely covered by DES

Sakurai et al. Am J Cardiol 2005;96:1251–1253.

FMRP 2016 |

DCB-BTK Evidence: The LEIPZIG Registry

Single Center Registry • 104 Patients (CLI 82.6%) • Diabetes 73% • Mean lesion length 17 cm • CTO’s 62%

IN.PACT Amphirion* vs. matched PTA historical cohort**

* Schmidt A et al. J Am Coll Cardiol. 2011 Sep 6;58(11):1105-9 ** Schmidt A et al. Catheter Cardiovasc Interv. 2010 Dec 1;76(7):1047-54

FMRP 2016 |

DCB-BTK Evidence: The LEIPZIG Registry

Single Center Registry • 132 Patients (CLI 100%) • Diabetes 100% • Mean lesion length 13 cm • CTO’s 80%

IN.PACT Amphirion vs. PTA in CLI DM patients

Liistro F et al. Ciculation. 2013 Aug 6;128(6):615-21

FMRP 2016 |

DCB-BTK Evidence: small RCT DCB-DES

Single Center RCT • 50 Patients (CLI + CI) • Mean lesion length : 14,8 cm (DCB) vs 12,7 cm (DES) ; p=0,33) IN.PACT Amphirion vs. DES : 6 m results

•Binary restenosis: 58% vs. 28% (p=0.045) •LLL: 1.35±0.2 vs. 1.15±0.3 (p=0.62) •TLR: 14.3% vs. 7.4 (p=0.21)

>50% Restenosis Length (cm) Group DES: 3.6 ± 1.5 Group PCB: 4.3 ± 1.6

p=0.16

P.M. Kitrou, MD, PhD – LINC 2014

Late Lumen Loss (mm) Group DES: 1.35 ± 0.2 Group PCB: 1.15 ± 0.3

P=0.62

FMRP 2016 |

DCB-BTK Evidence : BIOLUX P-II

• prospective, multi-center 1:1 RCT: DEB vs. POBA

• primary endpoints:

– clinical: 30-day Major Adverse Events (MAE)

– efficacy: 6-month target lesion primary patency

72 subjects enrolled (Rutherford 2-5)

DEB (N=36) Passeo-18 Lux

POBA (N=36) Passeo-18

30-day FU (N=35)

30-day FU (N=35)

6-month FU (N=33)

6-month FU (N=30)

12-month FU

24 M. Brodmann, MD – LINC 2014

FMRP 2016 |

• IN.PACT DEEP : prospective, multi-center 2:1 RCT: DEB vs. POBA

358 subjects enrolled (Rutherford 4-6)

DEB (N=239) POBA (N=119) In.Pact Amphirion standard PTA

Angio eligible = 168 DEB = 113 PTA = 54

Angio excluded = 191 DEB = 126 PTA = 65

Angiographic outcomes Clinical outcomes

25 Zeller et al. JACC 2014, 64 ; 15

DCB vs. PTA in C IN.PACT DEEP

FMRP 2016 |

DCB-BTK Evidence overall…

26

FMRP 2016 |

• DEVICE RELATED?

• STUDY DESIGN RELATED?

• BTK/CLI RELATED?

27

FMRP 2016 |

DEVICE RELATED?

DCB PTA p

12-month LLL (mm) 0.61±0.78 0.62±0.78 0.950

“Old” IN.PACT Amphirion “New” (Next Gen) IN.PACT Pacific Admiral

Coating method

Manually-coated on folded balloon

Automatically-coated on semi-inflated balloon

Lack of drug effect?

Animal studies confirmed balloon material can impact drug delivery: - New design delivered more drug to vessel Folds protect the drug - New design had less residual drug on balloon Better drug release

With the courtesy of T. Zeller, presented @ LINC 2015

FMRP 2016 |

• No standardized wound care protocols?

• No standardized major amputation protocols?

29

STUDY DESIGN RELATED?

Zeller T, JACC 2014;64:1568-76 – Liistro F, Circulation 2013;128(6):615-21

FMRP 2016 |

• Is there an essential fysiological difference between SFA and BTK? (IN.PACT SFA vs IN.PACT DEEP)

• Is there an essential difference between CLI and CI patients in PTX response/risk?

30

BTK/CLI RELATED?

FMRP 2016 |

Lutonix BTK

31

FMRP 2016 |

Lutonix BTK

32 Steiner S., presented @LINC 2016, Leipzig,Germany

FMRP 2016 |

New horizons….

• Direct drug delivery in the vessel wall

Bullfrog® micro-infusion device (Mercator Medsystems)

33

FMRP 2016 |

CONCLUSION • DES are effective for short BTK lesions in terms of primary

patency, fTLR & amputation free survival but randomized trials miss superiority in hard clinical outcome of RB-classification shift & woundhealing.

• There is no proven clinical advantage across all studies between ANY DCB & control groups.

• The lack of wound treatment-/amputation protocols are partially responsable for these issues

• Further research with new technologies is mandatory in the challenging DCB-BTK field

34

FMRP 2016 | 35

LINC AP 2016, Hong Kong

Drug delivery devices for BTK treatment

Koen Deloose , MD

Marc Bosiers Koen Deloose Joren Callaert

A.Z. Sint-Blasius, Dendermonde

Patrick Peeters Jürgen Verbist

W. Van den Eynde

OLV Hospital, Aalst

Lieven Maene Roel Beelen

R.Z. Heilig Hart, Tienen

Koen Keirse Bart Joos

Imelda Hospital, Bonheiden

Documents

Drug delivery devices for BTK treatment · FMRP 2016 | 1 LINC AP 2016, Hong Kong Drug delivery devices for BTK treatment Koen Deloose , MD Marc Bosiers Koen Deloose Joren Callaert