Transcript Document 7355617

BIOSENSORS-CLINICAL UPDATE
“LEADERS AND BEYOND”
John E Shulze, CTO
BIOSENSORS INTERNATIONAL GROUP
Jan 29, 2010
MY CONFLICTS
OF INTEREST ARE:
EMPLOYEE AND SHAREHOLDER
OF BIOSENSORS INTERNATIONAL
Biosensors Research:
• There is an unmet market need for DES that have a high effectiveness for suppression
on NH combined with a low incidence of late stent thrombosis upon cessation of
antiplatelet therapies.
• Development of Acute & SubAcute Thrombosis in stents is multifactorial and we should
expect that higher risk patients/procedures will result in more early thrombosis and
perhaps greater needs for antiplatelet therapy.
• However, Rapid healing, leading to complete endotheliazation and return of normal
endothelial function inside the stent we believe to be the most important factors in
reducing risk of VLST and maybe LST.
• Both PLA biodegradable coating technology and “polymer free” coating technologies
developed by Biosensors are intended to provide faster healing of the stent, 6-9 months
in the case of BioMatrix and similar to a bare stent in the case of the Biofreedom Stent.
BioMatrix™
The abluminal biodegradable polymer DES
Abluminal biodegradable coating
absorbed after 6-9 months*
10681-000 – Rev.01
PLA biodegradation
and BA9™ elution
4
* Data on file - molecular weight<10kDa
Biodegradable Polymer and Primer Coating
BioMatrix
BioMatrix II
BioMatrix Flex
FUTURE 1 and 2
STEALTH FIM
BEACON Registry
STEALTH PK
LEADERS
Stent
Stent
Stent
Primer: Parylene
Primer: Parylene
Matrix: Polylactic Acid
Matrix: Polylactic Acid
Source: S. Windecker, PCR 2008
No Primer
Matrix: Polylactic Acid
6
10717-000 – Rev.01
Trial Design
Stable and ACS Patients Undergoing PCI
Assessor-blind
1:1 Randomisation
N=1700 Patients
BES
SES
BioMatrix Flex N=850
Cypher Select N=850
1:3 Randomisation
Clinical F/U
N=640
Angio F/U
N=210
Clinical F/U
N=640
Angio F/U
N=210
1o endpoint:
CV death, MI, clinically-indicated TVR (9 month)
2o endpoints:
Death, CV death, MI, TLR, TVR
Stent thrombosis according to ARC
In-stent % diameter stenosis
Late loss, binary restenosis
Angiographic study:
7
DAPT recommended for 12 month
Primary Endpoint
Cardiac Death, MI and TVR @ 9 Months2
15
MACE %
Incidence (%)
Cumulative
Pnon-inferiority = 0.003
SES 10.5%
-12%
10
BES 9.2%
5
0
0
1
2
3
4
5
6
7
8
9
Months of Follow-up
BES reached its primary endpoint
8
2Windecker
S. et al., The Lancet 2008; 372 No. 9644: 1163-1173
MACE
20
BES
SES
1-year HR
2-year HR
0.88 [0.66 to 1.17]
P = 0.37*
0.84 [0.65 to 1.08]
P = 0.18*
15.4%
15
Δ 2.4%
12.1%
Δ 1.4%
%
10
13.0%
10.7%
5
0
0
3
6
9
12
Months
15
18
21
24
BES
857
804
795
777
760
742
731
725
716
SES
850
791
786
771
747
727
712
707
694
Number at risk
9
MACE = Cardiac Death, MI, or Clinically-Indicated TVR
* P values for superiority
Cardiac Death or MI
10
BES
SES
1-year HR
2-year HR
1.01 [0.70 to 1.45]
P = 0.95*
0.92 [0.66 to 1.27]
P = 0.59*
Δ0.8%
8.3%
6.9%
8
6.9%
%
9.1%
Δ0%
6
4
2
0
0
3
6
9
BES
857
804
797
788
780
772
764
760
752
SES
850
801
798
793
779
770
758
755
742
Number at risk
12
Months
15
18
*P values for superiority
21
24
10
Superior Strut Coverage
and Stent Apposition
3
•Lesions with at least 5% uncovered struts
50
40
p = 0.005
10 x
39.4
30
20
10
0
%
3.6
BES (N=26)
N strut = 6476
SES (N=20)
•Lesions with at least 5% malapposed struts
8
7
6
5
4
3
2
1
0
%
N strut = 4592
p = 0.04
6.7
20 x
0.3
BES (N=26)
N strut = 6476
SES (N=20)
N strut = 4592
BES with an abluminal biodegradable polymer achieved a 10 x better strut
coverage and a 20 x better stent apposition vs. SES with a symmetric
durable polymer at 9 months
3Di
Mario C., TCT 2008
11
Very Late Stent Thrombosis
Signs of Safety Benefits Beyond One
Year
12
Definite ST through 2 years
Zoom at 1% scale
+0.5%
3.0
BES
SES
2.2%
2.5
%
2.5%
2.0%
+0.2%
2.0
2.0%
1.5
1.0
0.5
0.0
0
3
6
9
12
15
18
21
24
Advantage in Complex Patients
14
Complex Patients – STEMI
12 Month MACE
p=0.07
BES
p=0.02
18
16
15.7
SES
-57%
14
MACE
12
p= 0.22
p=0.04
10
10
8
-77%
6.7
6.4
5
6
4
4.4
2.2
1.5
2
0
%
Cardiac death
MI
ci-TVR
MACE
Superior clinical outcomes
for the BES vs. SES up to 12 months
15
Buszman, P., PCR 2009
BIOSENSORS PRODUCT PIPELINE
BioFreedom: complete elimination of polymer,
Use of Surface texturing, yields more rapid drug
clearance to enhance healing:
BioMatrix
Biolimus A9 Elution from Stents
(MEDIUM: PBS pH 7.4/Tween, 37°C)
100%
90%
80%
BioMatrix Flex
•Enhance flexibility
•Increase stent retention
Cumulative Release (%)
•Changes to stent platform,
stent delivery catheter, coating
methods, and connector design,
for the Biomatrix Flex design…..
Polymerless
70%
60%
50%
40%
Biomatrix
30%
20%
10%
0%
0
10
20
30
Time (Hrs)
40
50
4 Month Late Lumen Loss
P< 0.0001
Late Loss mm (median)
P= 0.002
In-segment
P = 0.09
P = 0.35
P = 0.32
P= 0.09
P = 0.77
P = 0.99
P = 0.89
P = 0.71
P = 0.37
P = 0.19
Conclusions
• The biodegradable PLA polymer with complete release of drug and
polymer within 6-9 months differentiates the Biolimus eluting stents
from other DES with limus drugs eluted from durable polymers
• The abluminal surface coating manufacturing technology reduces the
polymer exposure compared with symmetric coatings
Conclusions
• The clinical trial program demonstrates that Biolimus A9 released from a
biodegradable PLA coating is a safe antiproliferative combination for use in
DES. The clinical studies in both simple and complex lesions have consistently
achieved or exceeded clinical endpoints compared to BMS and other approved
DES with:
-low MACE at various clinical endpoints up to and including 4 years
-low %DS & late loss
-no very late Thrombosis
• Clinical Trial data is currently available in the Biolimus program in over 4000
patients , and during 2010, additional >5000 patients (e-BioMatrix).
• Ongoing and planned clinical trials in an additional >5000 patients will evaluate
the durability of the BioMatrix results in large populations and in a wide range
of more complex patients and lesion subsets incl AMI.
Rue de Lausanne 29 – 1110 MORGES – Switzerland
Tel. (41) 0 21 804 80 00 – Fax (41) 0 21 804 80 01
[email protected]