Transcript slides

Orsiro: Biotronik’s PLLA/Sirolimus
Biodegradable DES Program
Ron Waksman, MD, FACC,FSCAI
Professor of Medicine, Georgetown University
Director, Cardiovascular Research Advanced Education
MedStar Heart Institute, Washington DC
Ron Waksman, MD
Consulting:
Biotronik, Inc.
Abbott Laboratories
Boston Scientific Corporation
Medtronic, Inc.
Merck and Company, Inc.
Honoraria:
Abbott Laboratories,
Boston Scientific Corporation
Merck and Company, Inc.
Medtronic, Inc.
Orsiro1 hybrid sirolimus eluting stent system
Passive component: PROBIO
• Silicon carbide2 layer that encapsulates the
stent surface, reducing ion release
Active component: BIOlute
• PLLA3 bioabsorbable polymer matrix
• Sirolimus (1.4 µg/mm2)
• Controlled drug release out to 3 months
• Asymmetric coating with greater
drug dose on abluminal side
In vivo drug release in minipig coronary arteries
(Ablumial thickness 7.4 µm)
100
Stent platform: PRO-Kinetic Energy
• Cobalt Chromium, L-605
• 60 µm struts
% Drug Release
90
80
70
60
50
40
30
20
10
0
1
Manufactured and distributed by BIOTRONIK
2 aSiC:H amorphous silicon carbide
3 Poly-L-lactide
0
10
20
30
40
50
60
Time (days)
Source: Data on file at BIOTRONIK
70
80
90
100
BIOlute contains a high molecular PLLA allowing precise
control of mechanical and pharmaceutical properties
Orsiro has an asymmetric coating and excellent polymer integrity
– Asymmetric coating allows greater drug
dose on abluminal side of stent strut
– Release kinetic is controlled by coating
and process design (no additional top
coatings are needed)
– Surface drug load of 1.4 µg/mm2 strut
surface
Mechanical properties are good
in general due to the mechanical
strength of the polymer
No flaking or pealing at
expansion areas
Source: SEM images from IIB Test Report 66/2009.
4
7.4μm
60μm
3.5μm
BIOlute contains sirolimus with an elution kinetic
optimized to release over 12-14 weeks
Orsiro elutes one of the most proven drugs for a DES
In vivo drug release in mini pig coronary arteries*
100
90
Drug load is 1.4
μg/mm2
Elution curve is inline with other
Limus-based stents
80
% Drug Release
In vivo studies show
complete sirolimus
release between 90100 days
70
60
50
40
30
20
10
0
0
*
10
20
Residual drug remaining of stent after explantation.
Source: Preclinical Orsiro animal studies, data on file, BIOTRONIK AG.
5
30
40
50
60
Time (days)
70
80
90
100
BIOlute degrades gently in less than 2
years to avoid increased inflammation
Elimination of the polymer removes the threat for polymer related longterm events
Real-time degradation of sirolimus loaded PLLA
4.0
Molecular weight [a.u.]
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
0
50
100
150
200
250
300
350
400
450
500
Time (days)
Source:
Preclinical Orsiro animal studies, data on file, BIOTRONIK AG.
6
Benign histology beyond polymer
degradation shown in mini-pigs
Minimal or no inflammatory response of vessel tissue upon degrading polymer
12m
24m
 Polymer coating visible at one year
36m
 Appearance different morphology; however,
analysis shows that there is no residual PLLA
 Similar to the Absorb platform, there is only a
morphometric imprint left
Differences among bioabsorbable and permanent
polymer DES
Pre-clinical histology, mean values at 28 day
Intimal area (mm)
Inflammation score
Orsiro
formulation
Fibrin score
PEVA/PBMA SES
PUR SES
PLLA SES
PLGA SES
BMS
Pre-clinical histology shows benign affects with
overlapped Orsiro devices
Pre-clinical histology
Mean values at 28 day
Inflammation score
Injury score
Fibrin score
No stent
Stent overlap
No overlap
Stent overlap
Compared to other drug eluting stents,
Orsiro has among the thinnest struts
Orsiro
Hybrid DES
SEM images
Strut
thickness
140 μm
91 μm
81 μm
60 μm
Polymer
thickness*
12.6 μm
4.8 μm
7.8 μm
7.4 μm
Total
thickness
153 μm
99 μm
95 μm
71 μm
* Only abluminal coating thickness represented.
10
First in Man Experience With a Drug Eluting Stent in
De Novo Coronary Artery Lesions (BIOFLOW-I)
Study Design
DESIGN: Prospective, multi-centre, nonrandomized, first in man trial
OBJECTIVE: To assess the safety and clinical
performance of the ORSIRO hybrid drug eluting
stent in patients with single de-novo coronary
artery lesions
CLINICAL COORDINATING
INVESTIGATOR:
Prof. Martial Hamon,
University Hospital of Caen, France
PRINCIPAL INVESTIGATORS:
Dr. Rodica Niculescu, MD, PhD, FESC
Dr. Dan Deleanu, MD, FESC
Primary Endpoint
In-stent late lumen loss at 9 months by QCA
30 patients enrolled July 2009
in 2 clinical sites in Rumania
Clinical follow-up at 1
month
Clinical & angiographic
follow-up at 4 months
Clinical & angiographic
follow-up at 9 months
Clinical follow-up at
12, 24 & 36 months
Baseline clinical characteristics
Patient demographics show multiple co-morbidities and
moderate level of diabetics
N=30
Age, years
58.10 yrs ± 9.80
Male sex
60.0%
18/30
Hyperlipidemia
93.3%
28/30
History of MI
73.3%
22/30
Hypertension
66.6%
20/30
Smoker
53.3%
16/30
Diabetes
23.3%
7/30
CHF
20.0%
6/30
Baseline lesion characteristics
Lesion characteristic show 1/3 of complex lesions with high
device success
Pre-Procedure
N=30
RVD (mm)
2.75 ± 0.34
MLD (mm)
0.95 ± 0.29
% Diameter stenosis
Mean Lesion length (mm)
Procedural
Stent length per lesion (mm)
Stent diameter per lesion (mm)
Direct stenting
Device success*
65.52 ± 9.47
11.71 ± 4.40
N=30
19.93 ± 5.33
3.08 ± 0.37
20.0%
100.0%
* Defined as In-Stent < 30% residual stenosis by offline QCA
Lesion Type
6.7%
A
26.7%
40.0%
26.7%
B1
B2
C
Angiographic follow-up results
Primary Endpoint
Late Lumen Loss
@ 9 Months
4-month
FUP
9-month
FUP
2.81 ± 0.28
2.81 ± 0.30
In-stent (mm)
2.50 ± 0.36
2.56 ± 0.38
In-segment (mm)
2.20 ± 0.35
2.21 ± 0.31
In-stent (%)
15.19 ± 4.55
13.60 ± 4.27
In-segment (%)
23.66 ± 9.80
23.55 ± 8.06
In-stent (mm)
0.12 ± 0.19
0.05 ± 0.22
In-segment (mm)
0.06 ± 0.23
0.05 ± 0.26
In-stent (mm)
0%
0%
In-segment (mm)
0%
0%
RVD (mm)
Minimal Lumen Diameter
Diameter Stenosis
0.05±0.22
0.05±0.26
Late Loss
Binary Restenosis
Clinical outcomes at 9 months
9-month clinical results
N
%
MACE
2
6.7
Cardiac Death
0
0.0
MI
0
0.0
Stent thrombosis
0
0.0
TLR (clinically driven)
2
6.7
MACE defined as:
Composite of cardiac death, MI attributed to the target vessel, stent thrombosis and clinically driven
target lesion revascularization
Clinical strategy for the Orsiro will collect
comparative and long-term data
Imperative: prove equivalence to the market leader and longterm safety
Study
design
– A prospective, multi-centre, single
treatment clinical trial
– Endpoint: LLL 9 months, N=30
– A prospective, multi-center, non-inferiority,
randomized study, Orsiro vs. Xience Prime
– Endpoint: LLL at 9 months, N=440
Clinical
strategy
– FIM study, results submitted to TÜV in
the CE-mark approval process
– Comparative, non-inferiority trial testing
safety and effectiveness
Study
design
– A prospective, multi-centre, single
treatment clinical registry
– Endpoint: LLL at 9 months, N=120
– A prospective, multi-centre, single
treatment clinical registry
– Endpoint: TLF at 12 months, N=1,000+
Clinical
strategy
– Pivotal trial for market approval in India,
testing safety and effectiveness
– All comers open label real world evaluation
BIOTRONIK-Safety and Clinical Performance of the Drug
Eluting Orsiro Stent in the Treatment of Subjects With single
de novo Coronary Artery Lesions (BIOFLOW-II)
Study Design
DESIGN: A prospective, multicenter,
international, two-arm, non-inferiority,
randomized controlled clinical study enrolling
up to 440 subjects. All subjects will be
randomized 2:1 to receive the BIOTRONIK
Orsiro or the Abbott Xience Prime™
OBJECTIVE: To compare the BIOTRONIK
Orsiro with the Abbott Xience Prime™ with
respect to in-stent Late Lumen Loss (LLL) in a
non-inferiority study in de novo coronary
lesions at 9 months.
COORDINATING INVESTIGATORS:
Prof. Stephan Windecker
Head of Interventional Cardiology
University Hospital Bern, Switzerland
Dr. Thierry Lefevre
Head of Interventional Cardiology
Hospital Jacques Cartier, Massy, France
440 patients
Enrollment started July 2011
2:1
Xience
PrimeTM
Orsiro
Clinical follow-up at 1 month
Clinical, angiographic,
IVUS* and OCT* follow-up
at 9 months
* Pre specified sub groups
with 60 patients in each
Clinical follow-up at 12 months
Clinical follow-up annually
out to 5 years
Primary Endpoint
-
In-stent late lumen loss at 9 months post procedure by QCA analysis
Patient eligibility
Inclusion Criteria
- Subject has provided a written
informed consent
- Single de novo lesion with ≥
50% and <100% stenosis in up
to 2 coronary arteries
- The target lesion length is ≤ 26
mm
- The target reference vessel
diameter is ≥ 2.25 mm and ≤
4.0 mm
Source: M. Hamon, EuroPCR 2011, LBT presentation.
-Exclusion Criteria
- LVEF ≤ 30%
- Evidence of myocardial
infarction within 72 hours prior
to index procedure
- Unprotected left main coronary
artery disease (stenosis >50%)
- Three-vessel coronary artery
disease at time of procedure
- Thrombus in target vessel
- Ostial target lesion (within 5.0
mm of vessel origin)
- Target lesion involves a side
branch > 2.0 mm in diameter
- Heavily calcified lesion
- Target lesion is located in or
supplied by an arterial or
venous bypass graft
BIOTRONIK VI invests in clinical trials –
coronary trials
STATUS 01/2013
Orsiro
BIOFLOW-II
BIOFLOW-I
Product
 Orsiro
Study Design
 FIM
Patients
 30/30
Product
 Orsiro
Study Design
 International, RCT 2:1
vs. Xience Prime
Patients
 458/440
BIOFLOW-III
BIOFLOW-India
Product
 Orsiro
Product
 Orsiro
Study Design
 International registry,
incl. subgroup
analysis
Study Design
 Indian registry
Patients
Patients
 120/120
 1,300/1,000+
BIOSCIENCE*
Product
 Orsiro
Study Design
 Swiss RCT 1:1 vs.
Xience Prime
Patients
 1,625/2,100
BIORESORT*
Product
 Orsiro
Study Design
 Dutch RCT 1:1:1 vs.
Synergy vs. Resolute
Patients
 103/3.500
* Research Grant
Orsiro Conclusions
• Biodegradable polymer technology has shown to
improve outcomes compared with the previous
gold-standard of durable polymer SES
• Orsiro Hybrid DES applies biodegradable polymer
based drug elution with an attractive platform,
and has shown promising results in a FIM study,
with high rates of diabetic patients and complex
lesions
• BIOFLOW-II will provide further data on this
novel device by directly comparing angiographic
outcomes with durable polymer EES (Xience
PrimeTM)
THANK YOU for YOUR ATTENTION