Transcript MiStent-Technologyx - Clinical Trial Results

MiStent SES®
Program Technology and Clinical Data
Update
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
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
REDEFINING DES – CRYSTALLINE SIROLIMUS
WITH A RAPIDLY ABSORBED POLYMER COATING
MiStent Crystalline Sirolimus
Unique to MiStent SES, the sirolimus is maintained in a microcrystalline morphology for controlled and prolonged elution,
as opposed to use of an amorphous, rapid-release form of the
drug.
MiStent Thin-Strut Stent
• Cobalt-chromium
• Highly deliverable (64 microns)
Reference: Carlyle et al, JCR 162 (2012) 561–567.
Strut Thickness (µm)
MISTENT SES: COMPARATIVE STRUT THICKNESS
BVS
150µm
BioMatrix
Flex
120µm
Resolute
Integrity
89µm
PROMUS
Element
81µm
XIENCE V
81µm
SYNERGY
74µm
MiStent
64µm
Adapted from K. Dawkins, CRT 2013.
Thinner struts are associated with more rapid healing and lower risk of acute thrombogenicity
Kolandaivelu, K., et al. Circulation 2011, 123(13), 1400-1409.
DRUG DELIVERY VS POLYMER DISSOLUTION
MiStent SES – Crystalline drug presence in the
tissue after elimination of polymer
• Minimizes duration of inflammatory effect
of polymer
• Retains anti-restenotic drug for 3X longer
than polymer is present
References:
Carlyle et al, JCR 162 (2012) 561–567.
Adapted from Dawkins TCT2014 & product websites
UNIQUE MECHANISM OF DRUG DELIVERY
Crystalline sirolimus 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 struts1
1 Deconinck E,
et al. Pharmaceutical Aspects of Drug Eluting Stents. Journal
of Pharmaceutical Sciences, 97(12), 5047-5060 (2008).
DESSOLVE I: STUDY DESIGN
First-in-Human, 30 patients, 5 sites
PROCEDURE
30D
4M
6M
4M (n=10)
Angio, IVUS, OCT
Enrolled
(n=30)
5 sites
6M (n=10)
8M
12M
18M
2Y
3Y
8M
(n=30)
12M
(n=30)
18M
2, 3, 4, 5Y
(n=30)
Clinical
Clinical
Follow-Up
Clinical
Long-term
Clinical
Follow-up
Angio, IVUS, OCT
8M (n=10)
Angio, IVUS, OCT
(n=27)
4Y
5Y
Angio,
IVUS,
OCT
– Mechanistic design to investigate quality of vessel healing
• 4, 6, 8-month data - angiography, IVUS, OCT
• 18-month data - angiography, IVUS, OCT
4-Year
Completed
Ormiston, J., et al. (2013). JACC Cl 6 (10), 1026-1033.
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
MACE
TLF
1 year
3.3% (1/30)
0% (0/30)
2 years
3.4% (1/29)
0% (0/29)
3 years
6.9% (2/29)
0% (0/29)
4 years
10.3% (3/29)
0% (0/29)
DESSOLVE 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 months
• No evidence of definite neoatherosclerosis at
18 months
Median
% Strut
Coverage
4-Month
Group
6-Month
Group
8-Month
Group
18-Month
Group
93%
97%
96%
100%
Thin homogeneous
tissue coverage
References: Ormiston J, et al. JACC CI 2013
Attizzani G, et al. Am J Card 2013
DESSOLVE II: STUDY DESIGN
2:1 RCT design for superiority of in-stent LLL at 9 months with Endeavor
184 patients at 26 sites
PROCEDURE
2:1 RCT
26 sites
30D
6M
9M
9M - MiStent SES
Angio, OCT, EFT, Clinical
Endeavor
n=61
12M
n=175
Clinical
Follow-Up
MiStent SES
n=123
12M
2Y
3Y
4Y
5Y
2, 3, 4, 5Y
Long-term
Clinical
Follow-up
9M - Endeavor
Angio, OCT, EFT, Clinical
MiStent SES LLL was significantly lower than
Endeavor at 9 months
0.27 ± 0.46 vs 0.58 ± 0.41 P<0.001
4-Year
Completed
Wijns W et al. EuroInterv 2015;10:1383-1390
DESSOLVE II: 4-Year Clinical Outcomes
P=0.27
P=1.00
P=0.72
P=0.18
P=1.00
P=0.31
P=0.33
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
Angiography In-Stent Late Lumen Loss
Results in low progression of target lesion
revascularization (TLR) at 4 Years
CD-TLR Over Time
N=152
Ormiston, J., et al. (2013). JACC Cl 6 (10), 1026-1033
Data on file - Micell
Comparison of Late-Term TLR with EES
Lansky, Byrne, et al. EuroPCR 2015
ONGOING CLINICAL STUDIES
Building on the success of the DESSOLVE I and II studies,
three additional studies initiated in 2015
China Approval Study
RCT vs Tivoli DES
N = 400 pts
DESSOLVE III Study
9-Month LLL, 12-Month TLF
Initiated Q2 2015
12-Month TLF
Post-Marketing RCT vs Xience
N = 1400 pts
Enrollment completed 12/2015
DESSOLVE III Sub-Study
Superiority for progression of
NIH over time
OCT RCT Sub-Study
N = 60 pts
Initiation Q4 2015
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 years
• MiStent 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
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