OrbusNeich Medical Group Holdings Limited · HKEX:6929
OrbusNeich Medical — Singapore Live 2006
50 slides from OrbusNeich Medical's conference presentation, Feb 27, 2006
Slide 1: Genous Bio-engineered R stent: Results of the HEALING II Study
Genous Bio-engineered R stent Endothelial Progenitor Cell Capture Technology Results of the HEALING II Study Robbert de Winter, MD, PhD Academic Medical Center Amsterdam, The Netherlands on behalf of the HEALING II Investigators Singapore Live, February 27, 2006
Slide 2: The HEALING Concept
The HEALING Concept • Why a new concept for coronary stenting? • What is the HEALING concept? • What data exist so far? • What are the future plans?
Slide 3: The HEALING Concept
The HEALING Concept • Why a new concept for coronary stenting? • What is the HEALING concept? • What data exist so far? • What are the future plans?
Slide 4: Brachytherapy Drug-eluting Stent
Brachytherapy Drug-eluting Stent
Slide 5: Stent Thrombosis in High Risk Groups
Centro cure Stent Thrombosis in High Risk Groups Columbus '" 1 c a t 41 . we la Rtn KO ON . y ~ ‘aal: \< ~ Renal failure (OR=11.5), bifurcation (7.2) prior brachyRx (4.2), diabetes (3.4), > and low LVEF (1.1). 3.2% eee 2.6% 2.0% CoLuMBIA UNIVERSITY CARDIOVASCULAR 0) Mepican CENTER Met 2 a0 4 RESEARC
Slide 6: Incidence, Predictors, and Outcome of Thrombosis After Drug-Eluting Stents
Incidence, Predictors, and Outcome of Thrombosis After Successful Implantation of Drug-Eluting Stents Toannis lakovou, MD Thomas Schmidt, MD Erminio Bonizzoni, PhD Lei Ge, MD Giuseppe M. Sangiorgi, MD Goran Stankovie, MD Flavio Airoldi, MD Alaide Chieffo, MD Matteo Montorfano, MD Mauro Carlino, MD l
Slide 7: We need a safer DES!
We need a safer DES! “| gotta have my Plavix”
Slide 8: The HEALING Concept
The HEALING Concept • Why a new concept for coronary stenting? • What is the HEALING concept? • What data exist so far? • What are the future plans?
Slide 9: A new paradigm for the prevention of restenosis?
A new paradigm for the prevention of restenosis? Rather than intervening locally using cytotoxic or cytostatic pharmacological compounds to prevent specific events which contribute to the occurrence of an over-exuberant healing response (DES) …promote the establishment of a functional endothelial mo
Slide 10: Endothelial progenitor cells
Endothelial progenitor cells The presence of endothelial progenitor cells (EPCs) in the circulating blood was first described by Asahara et al in 1996. EPCs are bone marrow derived and circulate in the adult. They have the ability to differentiate into mature, functional endothelial cells. Rosenzwei
Slide 11: hours
12 hours © Orbus MT Inc.
Slide 12: Bio-engineering the stent surface
Bio-engineering the stent surface
Slide 13: In vivo: SEM 1 Hr Post Porcine Coronary Artery Implantation (BMS)
In vivo : SEM 1 Hr Post Porcine Coronary Artery Implantation (BMS)
Slide 14: SEM: 1 Hr After Implantation (Genous)
SEM: 1 Hr After Implantation (Genous)
Slide 15: 48 hour explant
48 hour explant bare metal GENOUS: EPC capture M. Kutryk, MD, PhD, St Michael’s Hospital, Toronto, Canada, balloon injured pig arteries
Slide 16: 28-Day Histology – Porcine
28-Day Histology – Porcine BMS Typical neo-intimal response to stent injury with evidence of immature intima and remaining active fibrin. Complete healing with mature neo- intima. Genous
Slide 17: Ex vivo baboon AV shunt model
Ex vivo baboon AV shunt model Genous and bare metal stent Study Design • Baboon chronic ex vivo AV shunt • Platelets labeled with 111In • Gamma camera count recorded every 5 min • Flow regulated at 100cc/min through shunt • SEM observation after “cooling off” • No anticoagulation or antiplatelet the
Slide 18: Baboon AV shunt 111In labeled platelet deposition
Baboon AV shunt 111In labeled platelet deposition Run 1 Run 2 Genous adherent platelets vs BMS Terminated at 65 min due to BMS obstruction 93% reduction at 60 min 97% reduction at 65 min 79% reduction at 120 min S Hanson
Slide 19: SEMs after AV shunt study
SEMs after AV shunt study • Bare metal sent with flow occluding thrombus • Genous widely patent Bare metal stent Genous at 2 hours at 65 minutes S Hanson & R Virmani, MD, CV Path, Gaithersburg, MD, USA
Slide 20: Genous Technology
Genous Technology • Accelerated Healing • Protects Against Thrombus • Minimizes Restenosis • Safety Profile Over Current DES
Slide 21: The HEALING Concept
The HEALING Concept • Why a new concept for coronary stenting? • What is the HEALING concept? • What data exist so far? • What are the future plans?
Slide 22: HEALING II study design
HEALING II HEALING-FIM: Safety of the EPC stent in 16 patients with stable angina HEALING II study design: Multi-centered, prospective, non-randomized trial 63 patients; 10 invited centers (NL, B, D) Enrollment initiated May 2004; completed October 2004 Objective: Demonstrate the safety and efficacy
Slide 23: HEALING II participating centers
HEALING II participating centers P.W. Serruys, Erasumus University MC, Rotterdam, Principal Investigator P. den Heijer, Amphia Ziekenhuis, Breda B. Rensing, Sint Antonius Ziekenhuis, Nieuwegein R. de Winter, Academisch Medisch Centrum, Amsterdam M. Rau, Kerckhoff Herz Zentrum, Bad Nauheim H. Mudra,
Slide 24: Patient characteristics
Patient characteristics N 63 Male 42 (67%) Age 61 ± 10 years Hypertension 29 (46%) Diabetes 8 (13%) Hyperlipidemia 42 (67%) Current smoking 26 (41%) Family history 33 (52%) Unstable angina 17 (27%) Previous MI 15 (24%) Previous PCI 6 (10%)
Slide 25: Baseline characteristics and features
Baseline characteristics and features Location Angiographic features LAD 25 (40%) Lesion length (mm) 9.83±3.21 RCA 24 (38%) Reference vessel diameter (mm) 2.63±0.43 LCX 14 (22%) Minimal luminal diameter (mm) 0.98±0.24 Diameter stenosis (%) 62±9 Lesion type Procedure characteristics % A 0 (0%) Thromb
Slide 26: Can the individual peripheral blood level of EPCs influence the result?
Can the individual peripheral blood level of endothelial progenitor cells (EPCs) influence the result? Various studies have shown that patients with CAD revealed reduced levels and function of EPCs, which correlated with CAD risk factors (Circ.Res.(89) 2001; NEJM (348) 2003; Kidney Int.(67) 2005). T
Slide 27: Detection of EPCs by direct flow cytometric analysis of whole blood
Detection of EPCs by direct flow cytometric analysis of whole blood Live gate Leukocyte gate CD34 gate 1000 1000 1000 99,5 99.5 . 99.5 % Side Scatter Side Scatter 800 Side Scatter 800 800 600 600 600 400 00 400 400 0,027 % 200 200 200 0 0 0 10 0 10 1 10 2 10 3 10 4 0 1 2 3 4 100 1 10 10 2 10 3 4 10
Slide 28: Correlation of late loss index and circulation EPC titer at 6 months
Correlation of late loss index and circulation EPC titer at 6 months Similar findings with IVUS analysis R = 0.727 PW Serruys & HH Duckers, TCT 2005
Slide 29: Correlation of late loss index and circulation EPC titer at 6 months
Correlation of late loss index and circulation EPC titer at 6 months Similar findings with IVUS analysis R = 0.727 PW Serruys & HH Duckers, TCT 2005
Slide 30: HEALING II – late loss at 6 months
HEALING II – late loss at 6 months H2 Overall Avg 0.76mm (n=56) Std Dev 0.37mm Low EPC Avg 1.04mm (n=24) Std Dev 0.30mm p < 0.001 Normal EPC Avg 0.48mm (n=25) Std Dev 0.21mm PW Serruys & HH Duckers, TCT 2005
Slide 31: Correlation of late loss index and circulation EPC titer at 6 months
Correlation of late loss index and circulation EPC titer at 6 months Similar findings with IVUS analysis PW Serruys & HH Duckers, TCT 2005
Slide 32: Correlation of late loss index and circulation EPC titer at 6 months
Correlation of late loss index and circulation EPC titer at 6 months No Statin Tx PW Serruys & HH Duckers, TCT 2005
Slide 33: HEALING II Major Adverse Coronary Events (6 months)
HEALING II Major Adverse Coronary Events (6 months*) H2 overall Low EPC Normal EPC (n=63) (n=24) (n=25) Cardiac Death 1.6 % 0.0 % 0.0 % MI 0.0 % 0.0 % 0.0 % CABG 0.0 % 0.0 % 0.0 % TLR (Clinically Driven) 6.3 % 16.7 % 0.0 % MACE 7.9 % 16.7 % 0.0 % Binary Restenosis (n=56) 16.1 % 29.2 % 0.0% no MACE a
Slide 34: HEALING II Major Adverse Coronary Events (9 months)
HEALING II Major Adverse Coronary Events (9 months*) H2 overall Low EPC Normal EPC (n=63) (n=24) (n=25) Cardiac Death 1.6 % 0.0 % 0.0 % MI 0.0 % 0.0 % 0.0 % CABG 0.0 % 0.0 % 0.0 % TLR (Clinically Driven) 6.3 % 16.7 % 0.0 % MACE 7.9 % 16.7 % 0.0 % No additional events since 6 month visit; no subacute
Slide 35: Conclusions
Conclusions EPC titer correlates with angiographic and clinical outcome Normal levels of circulating EPCs result in significantly lower angiographic loss and favorable clinical outcomes TLR/TVR events are restricted to the low EPC group. Patients not on statins are generally restricted to the low EP
Slide 36: Conclusions
Conclusions The safety of the Genous stent has been established as illustrated by: – MACE rate at 9 months is lower than bare metal stents and similar to drug eluting stents. – No stent thromboses reported to date in the HEALING II Study. – TLR rate at 9 months is comparable to drug eluting stents a
Slide 37: The HEALING Concept
The HEALING Concept • Why a new concept for coronary stenting? • What is the HEALING concept? • What data exist so far? • What are the future plans?
Slide 38: HEALING Clinical Development Program
HEALING Clinical Development Program Statin Dosing and EPC Level Study Multi-center study designed to evaluate the relationship of statins and EPC levels. Statin-naive CAD patients will receive different doses of atorvastatin followed by serial measurements of EPCs. e-HEALING Multi-center (100-120 s
Slide 39: HEALING Clinical Development Program
HEALING Clinical Development Program HEALING III Multi-center, randomized, prospective trial designed to assess the safety and effectiveness of the Genous Bio-engineered R stent, in conjunction with optimal statin therapy, in the treatment of patients with de novo native coronary artery lesions. HEA
Slide 40: Why Registries?
Why Registries? Registries reflect the “real world” “Registries can serve to generate a hypothesis, which could be confirmed by a randomized trail with adequate power The “Ideal” Registry: enrolls “all comers” high number of patients comprehensive monitoring follow up rate not lower than randomized
Slide 41: e-HEALING: Objectives
e-HEALING: Objectives Collect post market surveillance data on patients: - receiving at least one Genous Bio-engineered R stent - with “On Label” indication (according to the Instructions for Use) - receiving at least two weeks of statin therapy at the time of stenting Assess clinical outcomes and s
Slide 42: e-HEALING Internet Registry
e-HEALING Internet Registry Registries reflect the “real world” Global, Internet-based, multicenter, prospective, non-randomized registry Principal Investigators: - Prof. Silber, Kardiologie Praxis, München - Dr. de Winter, AMC, Amsterdam CRO: Cardialysis, Rotterdam Internet data input: KIKA Medical
Slide 43: e-HEALING Study Objective
e-HEALING Study Objective Capturing Post Market Surveillance safety data on the use of the Genous stent in patients on 14 days “standard care” statin therapy. Primary Endpoint Target Vessel Failure (TVF) at 12M Secondary Endpoints Pre and post procedure angiographic success Procedural success MACE u
Slide 44: e-HEALING Patients Registered by Country
e-HEALING Patients Registered by Country Total enrollment: 382 patients Interim results as of February 26, 2006; n=382
Slide 45: e-HEALING: Patient Demographics
e-HEALING: Patient Demographics Males – 74.4% Previous MI – 35.5% 64 years (range 36-91) Previous PCI – 28.0% Diabetics – 28.8% Previous CABG – 5.6% Current Smokers – 24.0% Previous Stroke – 4.5% Hypercholesterolaemia – 77.3% CHF – 3.2% Hypertension – 67.2% Family History – 30.9% Interim results as
Slide 46: e-HEALING: Ischemic Status
e-HEALING: Ischemic Status Unstable angina 39.7% Stable angina 44.5% Silent ischemia 17.7% Interim results as of February 26, 2006; n=382
Slide 47: Indication for PCI
Indication for PCI Non STEMI (ongoing instability) 8.3% Unstable angina (ongoing instability) 14.7% Post STEMI (stabilised) 13.3% Post Non STEMI (stabilised) 10.1% Post unstable angina (stabilised) 6.7% Elective PCI (stable angina and/or 44.0% documented ischemia) Others 3.7% Unknown 0.8% Interim re
Slide 48: Lesion Characteristics
Lesion Characteristics Number of stents/lesion 1.1 stents/lesion Number of lesions treated/pt 1.38 lesions/pt Number of stents per patient 1.42 stents/patients Lesion classification De novo 95.6% Restenotic 4.4% Reference of vessel diameter pre Lesion length (mm) procedure (mm) Mean 14.8 Mean 3.1 St
Slide 49: Deviations to Date
Deviations to Date • Not on statins for at least 2 weeks before procedure 15.1% • Patient with diffuse disease or poor flow distal to lesion 24.3% • Q wave MI <= 3 days 1.8% • Non Q wave MI <= 3 days 1.6% • Previous stent implanted is a drug eluting stent 3.9% • Anti platelet and/or anticoagulant th
Slide 50: THANK YOU for your kind attention!
THANK YOU for your kind attention!
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