The first establishment of early healing profile & 9-month outcomes of a new “polymer-free”

Biolimus-A9 drug-coated-stent by Longitudinal Sequential OCT Assessments:

The EGO-BioFreedom Study

EGO-BioFreedom Study

Stephen WL LEE; Kelvin KW CHAN; Simon CC LAM; Shun-Ling KONG; Frankie CC TAM; Michael KL Wong; Anthony YT WONG; Arthur SY YUNG; Catherine P SHEA; Li-Wei ZHANG; Yui Ming LAM; Gary Mintz*, Akiko Maehara*

Division of Cardiology, University of Hong Kong, Queen Mary Hospital, Hospital Authority, Hong Kong* Columbia University Medical Center, Cardiovascular Research Foundation, New York, USA

Potential conflicts of interest

Speaker's name: Stephen Wai-luen LEE (Queen Mary Hospital, Hong Kong)

I do not have any potential conflict of interest

• BioFreedom DES were provided by Biosensors Ltd. as an investigational device.• CRF Core Laboratory Analysis was supported by a limited grant from Biosensors Ltd..

• DES reduce restenosis but require prolonged DAPT, with adverse development of “late stent failure”. BMS may be preferred in some situations.

• Poor stent healing and late stent failure (thrombosis, late catch-up and accelerated neo-atherosclerosis) have been reported to be associated with polymer hypersensitivity and / or drug toxicity after DES implantation.

• The new “polymer-free” abluminally coated Biolimus-A9 BioFreedom Stent (Biosensors Europe SA, Morges, Switzerland), with a stainless steel BMS luminal surface was studied.

• A potential benefit of better early healing (as reflected by degree of rapid early strut coverage by OCT) while retaining its efficacy as a DES (9M healing and neointimal suppression).

• This study is a first of its kind for a polymer-free drug-coated stent using longitudinal sequential OCT assessments.

Study AimEGO-BioFreedom Study

Luminal surface: stainless steel bare metal surface

120 micron thick corrugated ring strut

Abluminal surface: “polymer-free” micro-structured crevices harboring Biolimus drug (BA9)

Novelty of stent design

BA9, a very high lipophilic limus drug, allowing sustained high tissue concentration for neo-intimal suppression

BioFreedom Stent

Release kinetics: within 28 days 98% of BA9 would be transferred to the tissue of vessel wall; after that essentially a BMS

EGO-BioFreedom Study

Aims, Design & Methods

Aims: To examine the benefits of the polymer-free BA9 Drug Coated Stent: -• Early (1-5M) strut coverage: healing profile & guiding DAPT• 9M OCT follow-up: neointimal metrics and morphology as a DES• Clinical outcomes (12 months)

Method: 3 Longitudinal sequential OCT assessments to monitor (a) progression of strut coverage and (b) morphological changes of neointima.

* NIT, NIA, NIV denote neointimal thickness, area & volume by OCT

• Prospective single center • N = 100 (20:20:20:20:20) patients• 29% diabetic cases • Real world, all-comers except STEMI

Patients randomly assigned to 5 groups (1:1:1:1:1 ) Early OCT assessment for early healing profile

9-month OCT assessment for neointima metrics

1 month: 20 Patients

2 months: 20 Patients

3 months: 20 Patients

4 months: 20 Patients

9 months: 100 Patients

Baseline: 100 Patients

5 months: 20 Patients

Study Flow Charts & Status

Study Status: 100% OCT FU rate; study completed, pending core lab QCA results

BioFreedom Stent ImplantationBaseline OCT for best stent optimization

100% OCT FU rate4 ISR (TLR rate 4%)

106 lesions (128 stents)Mean stent length = 25.0±10.2mmMean stent diameter = 3.05±0.49mm

6 Category Coverage Classification (CRF Core Lab., frame by frame analysis)

A = Definitely uncovered. Strut not covered by tissue and both sides appear square.B = Uncovered with abnormal in-stent tissue (AIST). Strut covered by irregular tissue or fibrin, and both sides appear square.C = Partially uncovered. Strut partially covered by tissue but only one side has a smooth continuous shoulder.D = Covered (protruding). Strut covered by thin continuous tissue on both sides but still extending into the lumen. E = Covered (embedded). Strut covered by continuous tissue or neointima, and not interrupting the smooth lumen contour.F = Covered (proliferative). Strut covered with excessive growth of neointima with thickness > 0.3mm.

To ensure consistency & accuracy of visual assessment of early strut coverage !!

Early Healing Curve (1-5 months Coverage %)

Percentage strut coverage (Cat. D, E, F) increased progressively from 48.16% (minimum) at 1M to 97.14% (median) at 5M. In each group (20 patients) the variations of coverage were much higher in the earlier phases (1-2M), which were largely replaced by near complete coverage in the later months.

Early coverage is rapid with BF stents.

EGO-BioFreedom Study

EGO-BioFreedom Study

Repeated Measures Mixed Model

1-5 months(Total Strut No. = 23351)

9 months(Total Strut No. = 23239)

p-value

OCT Frame Number analyzed Median [Q1-Q3] 132 [104,164] 135 [106,161] 0.9111 (Min, Max) (70,350) (72,333) OCT Strut Number analyzed Median [Q1-Q3] 936 [719,1310] 924 [723,1241] 0.6694 (Min, Max) (456,2516) (496,2378) Neointimal Thickness (NIT) (mm) Median [Q1-Q3] 0.040 [0.030, 0.080] 0.110 [0.060, 0.180] <0.0001 (Min, Max) (0.000, 0.930) (0.000, 1.540) Mean Neointimal Area (NIA) (mm2) Median [Q1-Q3] 0.329 [0.135, 0.653] 1.050 [0.672, 1.394] <0.0001 (Min, Max) (0.000, 2.179) (0.19, 3.916)) Neointimal Volume (NIV) (mm3) Median [Q1-Q3] 7.931 [3.259, 15.516] 23.327 [13.722, 35.07] <0.0001 (Min, Max) (0.000, 100.616) (0.357, 124.682) Percentage Neointimal Volume* Median [Q1-Q3] 4.284 [2.143, 7.527] 13.032 [9.940, 16.816] <0.0001 (Min, Max) (0.000, 20.827) (0.216, 37.851)

Longitudinal Sequential OCT Assessments

Early (1-5 Months) versus 9 Months Results: • 9 months median strut coverage reaches of 99.55% [IQR 98.17 - 99.93; min. 85.41, max. 100].• More mature neointimal tissue (brighter and more homogeneous) was observed. • Median neointimal thickness (NIT) increased progressively from 1M to 5M at 0.04, 0.04, 0.04, 0.05, and

0.06mm, overall p=0.0028, respectively.• 9M NIT remained very low at 0.10mm [0.06 - 0.18] confirming efficacy of BioFreedom as a DES.• In-stent percentage neointimal volume increased from 4.28% in early months to 13.03% at 9M. • Mean FU duration is 468±192 days to date; 4 patients had ISR at 9 months requiring treatment (TLR rate = 4%).• No other MACE recorded. No ARC (definite or probable) late stent thrombosis has been recorded to date.

* Percentage Neointimal Volume = NIV/Stent Volume %

EGO-BioFreedom StudyRepresentative cases

Varying degree of coverage and changing neointimal morphology Longitudinal Sequential OCT Assessments

Worse scenario (Group 2) 2 BF stents

Optimal scenario (Group 2) 1 BF stent

Optimal baseline apposition 2M: some early coverage with minor positive remodeling

9M: still inadequate coverage with unhealthy neointima

Optimal baseline apposition with some thrombi

2M: good early coverage with young tissue

9M: fully covered struts with healthy neointima

EGO-BioFreedom Study

Study Summaries

• With core lab. adjudication, the BA9 BioFreedom Stent is the first “polymer-free” drug-coated-stent ever studied, with early healing profile established and neointima morphology changes over 9 months documented by longitudinal sequential OCT assessments.

• Favorable 9M OCT changes and good 12M clinical outcomes were recorded without occurrence of late stent thrombosis to date.

• This study is a proof of concept of the “polymer-free” approach (retaining neointimal suppression efficacy like any other DES having various polymer design); this approach could impose major impact on future new stent platform development.

• Establishment of early healing profile (early strut healing & coverage) could guide optimal duration of DAPT (BF above 70% by 2 months), allowing physicians to treat critically ill patients balancing stent thrombosis versus bleeding risk.

• Safety and efficacy: The polymer-free BioFreedom Stent appears to be a novel device in terms of early stent healing and 9 months neointimal suppression. Limitations:- (a) no control arm of another DES, and (b) need long-term clinical results for correlations.

Thank you