David . Kandzari. , MD. Monday, February 22. 11:41-11:48 pm. Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the . organization(s. ) listed below. ID: 636397
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Presentations text content in MiStent SES ® Program Technology and Clinical Data Update
Slide1
MiStent SES® Program Technology and Clinical Data Update
David
Kandzari
, MD
Monday, February 22
11:41-11:48 pm
Slide2
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the
organization(s
) listed below
Affiliation/Financial
Relationship Company
Grant/Research Support
Abbott
Vascular, Boston Scientific,
Medtronic
CardioVascular
,
Biotronik
,
Thoratec
Consulting Fees/Honoraria
Boston
Scientific Corporation,
Medtronic
CardioVascular
,
Micell
Major Stock Shareholder/Equity None
Royalty Income
None
Ownership/Founder
None
Intellectual Property Rights
None
Other Financial Benefit
None
Slide3
MiStent Crystalline SirolimusUnique to MiStent SES, the
sirolimus
is maintained in a
micro-crystalline morphology for controlled and prolonged elution, as opposed to use of an amorphous, rapid-release form of the drug.
REDEFINING DES – CRYSTALLINE SIROLIMUS WITH A RAPIDLY ABSORBED POLYMER COATING
MiStent
Thin-Strut Stent
Cobalt-chromium
Highly
deliverable (64 microns)
Reference: Carlyle et al, JCR 162 (2012) 561–567.
Slide4
MISTENT SES: COMPARATIVE STRUT THICKNESS
Strut Thickness (µm)
BVS
150µm
BioMatrix
Flex
120µm
Resolute
Integrity
89µm PROMUSElement 81µm
XIENCE V
81µm
MiStent 64µm
Thinner struts are associated with more rapid healing and lower risk of acute
thrombogenicity
Kolandaivelu
, K., et al.
Circulation
2011,
123(13), 1
400-1409.
Adapted from K. Dawkins, CRT 2013.
SYNERGY 74µm
Slide5
DRUG DELIVERY VS POLYMER DISSOLUTION
References: Carlyle et al, JCR 162 (2012) 561–567.
Adapted from Dawkins TCT2014 & product websites
MiStent SES – Crystalline drug presence in the tissue after elimination of polymer
Minimizes duration of inflammatory effect of
polymerRetains anti-restenotic drug for 3X longer than polymer is present
Slide6
UNIQUE MECHANISM OF DRUG DELIVERY
Crystalline
s
irolimus
provides sustained elution to limit disease progression
Controlled drug release from moment of deployment
MiStent SES
An initial uncontrolled burst of drug may delay re-endothelialisation
and coverage of the stent struts11 Deconinck E, et al. Pharmaceutical Aspects of Drug Eluting Stents. Journal of Pharmaceutical Sciences, 97(12), 5047-5060 (2008).
Slide7
DESSOLVE I: STUDY DESIGN
First-in-Human, 30 patients, 5 sites
Mechanistic design to investigate quality of vessel healing
4, 6, 8-month data - angiography, IVUS, OCT
18-month data - angiography, IVUS,
OCT
PROCEDURE
30D
4M
6M
8M
12M
18M
2Y
3Y
4Y
5Y
4M
(n=10)
Angio, IVUS
, OCT
6M
(n=10)
Angio, IVUS, OCT
8M
(n=10)
Angio, IVUS,
OCT
8M
(
n=30
)
Clinical
12M
(n=30)
Clinical
Follow-Up
(n=27)
Angio,
IVUS, OCT
18M
(n=30)
Clinical
Enrolled
(n=30)
5 sites
Ormiston
, J.,
et al
. (2013).
JACC Cl
6
(10),
1026-1033.
2
, 3, 4, 5Y
Long-term
Clinical
Follow-up
4-Year Completed
Slide8
DESSOLVE I: SAFETY AT 4 YEARS
No Target Lesion Failure
No
Target Lesion Related MACE 1 MI – Non-Target Vessel NQW-MI at 44 days 1 MI – Non-Target Vessel NQW-MI at 732 days 1 TVR at 1280 days No Stent Thrombosis
Imaging with OCT demonstrated thin, homogeneous coverage with high rates of stent strut coverage at 6 - 8 monthsNo evidence of definite neoatherosclerosis at 18 months
Thin homogeneous tissue coverage
Median
4-Month Group
6-Month Group8-Month Group18-Month Group% Strut Coverage93%97%96%100%References: Ormiston J, et al.
JACC CI
2013
Attizzani
G, et al.
Am J Card
2013
Slide10
DESSOLVE II: STUDY DESIGN
2:1 RCT design for superiority of in-stent LLL at 9 months with Endeavor
184 patients at 26 sites
2:1 RCT
26 sites
MiStent SES
n
=123
Endeavor
n=61
PROCEDURE
30D
6M
9M
12M
2Y
3
Y
4Y
5Y
9M
-
MiStent
SES
Angio, OCT
, EFT, Clinical
9M
- Endeavor
Angio, OCT, EFT, Clinical
12M
n=175
Clinical
Follow-Up
2
, 3, 4, 5Y
Long-term
Clinical
Follow-up
4-Year Completed
Wijns
W et al.
EuroInterv
2015;10:1383-1390
MiStent SES
LLL
was significantly lower than Endeavor at 9 months
0.27 ± 0.46
vs
0.58 ±
0.41
P
<0.001
Slide11
P=0.27
P=1.00
P=0.72
P=0.18
P=1.00
P=0.31
P=0.33
DESSOLVE II: 4-Year Clinical Outcomes
Slide12
12
DESSOLVE II: 4-Year Clinical Outcomes
The MiStent
®
Sirolimus Eluting Absorbable Polymer Coronary Stent System (MiStent SES) has received the CE Mark but is not approved for sale or use in the United States by the FDA.
Confidential
Slide13
ABSENCE OF LLL CATCH-UP TRANSLATES TO LOW TLR PROGRESSION
No Progression of In-stent Late Lumen Loss From
6/8
to 18 Months Follow Up
Results in low progression of target lesion revascularization (TLR) at 4 YearsAngiography In-Stent Late Lumen Loss
CD-TLR Over TimeOrmiston, J., et al. (2013). JACC Cl 6 (10), 1026-1033
Data on file - Micell
N=152
Slide14
Comparison of Late-Term TLR with EES
Lansky, Byrne, et al.
EuroPCR
2015
Slide15
ONGOING CLINICAL STUDIES
Building
on the success of the DESSOLVE I and II studies,
three
additional studies
initiated in 2015China Approval StudyRCT vs Tivoli DESN = 400 pts9-Month LLL, 12-Month TLFInitiated Q2 2015
DESSOLVE III Study
Post-Marketing RCT vs Xience
N = 1400 pts12-Month TLFEnrollment completed 12/2015
DESSOLVE III Sub-StudyOCT RCT Sub-StudyN = 60 ptsSuperiority for progression of NIH over timeInitiation Q4 2015
Slide16
SUMMARY OF MISTENT PERFORMANCE
MiStent converts to a BMS in 45 - 60 days and all polymer is absorbed in 90 days
Therapeutic levels of sirolimus in tissue is maintained beyond the polymer absorption due to use of crystalline drug
4-year pooled DESSOLVE I and II CD-TLR rate is 2.7%
No probable or definite ST through 4 yearsMiStent has no late catch-up resulting in a low progression of TLR over long-term follow-up potential for significant health economic benefits based on fewer f/u TLRs
Slide17
MiStent Design Capitalizing on Lessons Learned and Novel Discovery
1. There is an undesirable consequence of both extremes, when the scaffolding is removed or inordinately thick— we have experienced this with both thick struts stents but also
bioresorbable
scaffolding
2. Elution of drug from the polymer is only a limited component of controlled drug delivery—formulation of drug, dispersion throughout tissue, duration of effect and dwell time are all essential and yet underappreciated components 3. MiStent incorporates advantages of stent-based and balloon-based systems, representing delivery of stent coating and drug yet independent of stent scaffolding 4. Crystalline formulation of sirolimus permits more uniform dosing, without focal excess or minimal concentrations, and without initial burst of drug release 5. Both by flow of coating and delivery of crystalline drug, there is a distinct advantage of drug persistence after polymer dissolution
Download this presentation
DownloadNote - The PPT/PDF document "MiStent SES ® Program Technology and C..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Presentations text content in MiStent SES ® Program Technology and Clinical Data Update
MiStent SES® Program Technology and Clinical Data Update
David
Kandzari
, MD
Monday, February 22
11:41-11:48 pm
Slide2Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the
organization(s
) listed below
Affiliation/Financial
Relationship Company
Grant/Research Support
Abbott
Vascular, Boston Scientific,
Medtronic
CardioVascular
,
Biotronik
,
Thoratec
Consulting Fees/Honoraria
Boston
Scientific Corporation,
Medtronic
CardioVascular
,
Micell
Major Stock Shareholder/Equity None
Royalty Income
None
Ownership/Founder
None
Intellectual Property Rights
None
Other Financial Benefit
None
Slide3MiStent Crystalline SirolimusUnique to MiStent SES, the
sirolimus
is maintained in a
micro-crystalline morphology for controlled and prolonged elution, as opposed to use of an amorphous, rapid-release form of the drug.
REDEFINING DES – CRYSTALLINE SIROLIMUS WITH A RAPIDLY ABSORBED POLYMER COATING
MiStent
Thin-Strut Stent
Cobalt-chromium
Highly
deliverable (64 microns)
Reference: Carlyle et al, JCR 162 (2012) 561–567.
Slide4MISTENT SES: COMPARATIVE STRUT THICKNESS
Strut Thickness (µm)
BVS
150µm
BioMatrix
Flex
120µm
Resolute
Integrity
89µm PROMUSElement 81µm
XIENCE V
81µm
MiStent 64µm
Thinner struts are associated with more rapid healing and lower risk of acute
thrombogenicity
Kolandaivelu
, K., et al.
Circulation
2011,
123(13), 1
400-1409.
Adapted from K. Dawkins, CRT 2013.
SYNERGY 74µm
Slide5DRUG DELIVERY VS POLYMER DISSOLUTION
References: Carlyle et al, JCR 162 (2012) 561–567.
Adapted from Dawkins TCT2014 & product websites
MiStent SES – Crystalline drug presence in the tissue after elimination of polymer
Minimizes duration of inflammatory effect of
polymerRetains anti-restenotic drug for 3X longer than polymer is present
Slide6UNIQUE MECHANISM OF DRUG DELIVERY
Crystalline
s
irolimus
provides sustained elution to limit disease progression
Controlled drug release from moment of deployment
MiStent SES
An initial uncontrolled burst of drug may delay re-endothelialisation
and coverage of the stent struts11 Deconinck E, et al. Pharmaceutical Aspects of Drug Eluting Stents. Journal of Pharmaceutical Sciences, 97(12), 5047-5060 (2008).
Slide7DESSOLVE I: STUDY DESIGN
First-in-Human, 30 patients, 5 sites
Mechanistic design to investigate quality of vessel healing
4, 6, 8-month data - angiography, IVUS, OCT
18-month data - angiography, IVUS,
OCT
PROCEDURE
30D
4M
6M
8M
12M
18M
2Y
3Y
4Y
5Y
4M
(n=10)
Angio, IVUS
, OCT
6M
(n=10)
Angio, IVUS, OCT
8M
(n=10)
Angio, IVUS,
OCT
8M
(
n=30
)
Clinical
12M
(n=30)
Clinical
Follow-Up
(n=27)
Angio,
IVUS, OCT
18M
(n=30)
Clinical
Enrolled
(n=30)
5 sites
Ormiston
, J.,
et al
. (2013).
JACC Cl
6
(10),
1026-1033.
2
, 3, 4, 5Y
Long-term
Clinical
Follow-up
4-Year Completed
Slide8DESSOLVE I: SAFETY AT 4 YEARS
No Target Lesion Failure
No
Target Lesion Related MACE 1 MI – Non-Target Vessel NQW-MI at 44 days 1 MI – Non-Target Vessel NQW-MI at 732 days 1 TVR at 1280 days No Stent Thrombosis
MACETLF1 year3.3% (1/30) 0% (0/30)2 years3.4% (1/29) 0% (0/29)3 years6.9% (2/29)0% (0/29)4 years
10.3% (3/29)
0% (0/29)
Slide9DESSOLVE I: IMAGING RESULTS
Healing demonstrated by OCT
through
18
months OCT Results
Imaging with OCT demonstrated thin, homogeneous coverage with high rates of stent strut coverage at 6 - 8 monthsNo evidence of definite neoatherosclerosis at 18 months
Thin homogeneous tissue coverage
Median
4-Month Group
6-Month Group8-Month Group18-Month Group% Strut Coverage93%97%96%100%References: Ormiston J, et al.
JACC CI
2013
Attizzani
G, et al.
Am J Card
2013
Slide10DESSOLVE II: STUDY DESIGN
2:1 RCT design for superiority of in-stent LLL at 9 months with Endeavor
184 patients at 26 sites
2:1 RCT
26 sites
MiStent SES
n
=123
Endeavor
n=61
PROCEDURE
30D
6M
9M
12M
2Y
3
Y
4Y
5Y
9M
-
MiStent
SES
Angio, OCT
, EFT, Clinical
9M
- Endeavor
Angio, OCT, EFT, Clinical
12M
n=175
Clinical
Follow-Up
2
, 3, 4, 5Y
Long-term
Clinical
Follow-up
4-Year Completed
Wijns
W et al.
EuroInterv
2015;10:1383-1390
MiStent SES
LLL
was significantly lower than Endeavor at 9 months
0.27 ± 0.46
vs
0.58 ±
0.41
P
<0.001
Slide11P=0.27
P=1.00
P=0.72
P=0.18
P=1.00
P=0.31
P=0.33
DESSOLVE II: 4-Year Clinical Outcomes
Slide1212
DESSOLVE II: 4-Year Clinical Outcomes
The MiStent
®
Sirolimus Eluting Absorbable Polymer Coronary Stent System (MiStent SES) has received the CE Mark but is not approved for sale or use in the United States by the FDA.
Confidential
Slide13ABSENCE OF LLL CATCH-UP TRANSLATES TO LOW TLR PROGRESSION
No Progression of In-stent Late Lumen Loss From
6/8
to 18 Months Follow Up
Results in low progression of target lesion revascularization (TLR) at 4 YearsAngiography In-Stent Late Lumen Loss
CD-TLR Over TimeOrmiston, J., et al. (2013). JACC Cl 6 (10), 1026-1033
Data on file - Micell
N=152
Slide14Comparison of Late-Term TLR with EES
Lansky, Byrne, et al.
EuroPCR
2015
Slide15ONGOING CLINICAL STUDIES
Building
on the success of the DESSOLVE I and II studies,
three
additional studies
initiated in 2015China Approval StudyRCT vs Tivoli DESN = 400 pts9-Month LLL, 12-Month TLFInitiated Q2 2015
DESSOLVE III Study
Post-Marketing RCT vs Xience
N = 1400 pts12-Month TLFEnrollment completed 12/2015
DESSOLVE III Sub-StudyOCT RCT Sub-StudyN = 60 ptsSuperiority for progression of NIH over timeInitiation Q4 2015
Slide16SUMMARY OF MISTENT PERFORMANCE
MiStent converts to a BMS in 45 - 60 days and all polymer is absorbed in 90 days
Therapeutic levels of sirolimus in tissue is maintained beyond the polymer absorption due to use of crystalline drug
4-year pooled DESSOLVE I and II CD-TLR rate is 2.7%
No probable or definite ST through 4 yearsMiStent has no late catch-up resulting in a low progression of TLR over long-term follow-up potential for significant health economic benefits based on fewer f/u TLRs
Slide17MiStent Design Capitalizing on Lessons Learned and Novel Discovery
1. There is an undesirable consequence of both extremes, when the scaffolding is removed or inordinately thick— we have experienced this with both thick struts stents but also
bioresorbable
scaffolding
2. Elution of drug from the polymer is only a limited component of controlled drug delivery—formulation of drug, dispersion throughout tissue, duration of effect and dwell time are all essential and yet underappreciated components 3. MiStent incorporates advantages of stent-based and balloon-based systems, representing delivery of stent coating and drug yet independent of stent scaffolding 4. Crystalline formulation of sirolimus permits more uniform dosing, without focal excess or minimal concentrations, and without initial burst of drug release 5. Both by flow of coating and delivery of crystalline drug, there is a distinct advantage of drug persistence after polymer dissolution
Slide18Slide19