BuMA®

A Novel Biodegradable Polymer DES

with
Electro-Grafting (eG™) Coating Technology
and
Superior Endothelialization

Agus Harsoyo MD

Unit Clinical Cardiac Electrophysiology and Device Implantation

Department of Cardiology, Faculty of Medicine Universitas Indonesia,
Gatot Soebroto Indonesia Army Center Hospital
 DES challenge
Incomplete endothelial coverage → cause of late stent
thrombosis → as non-erodable polymeric drug-eluting stents
(DES).

autopsy studies of human coronary stents → re-

endothelialization of DES impaired → three to four month
period in bare metal stents → cause by an influence of the
drug, polymer or a combination of both.
Joner M et al. J. Am. Coll. Cardiol. 2006
 DES challenge
Incomplete endothelial coverage is suspected as the most likely cause of late
stent thrombosis, a recognized complication of the current generation of FDA
approved non-erodable polymeric drug-eluting stents (DES). Recent autopsy
studies of human coronary stents suggest that re-endothelialization of DES
impaired far beyond the three to four month period in bare metal stents
suggesting an influence of the drug, polymer or a combination of both.
 BuMA® Components
A Novel Sirolimus Eluting Stent with electro-Grafting technology

Electro-grafting base layer, Biodegradable Poly Lactic-co-

covalently bonded to stent Glycolic Acid (PLGA) drug carrier

Qian J et al. EuroIntervention 2014;10:806-814

Sirolimus Open cell stent platform

 eG™ Coating Technology*
What’s eG coating technology?

Electro-grafting: an eletrochemical process to create a

passive coating to the surface of metal.
 Ultra-thin (nanometric 150-200nm) organic (polymeric) layers;
 Grafting = covalent bonding to the stent surface = strong adhesion
 Hyper conformal and uniform on complex shapes.

Anchored polymer chains

Step
precursor molecules
Step
1 2 4-5nm
eG layer
150-200nm
2-3nm

electric current

* Technology originates from Massy, France (subsidiary of SINOMED)

 Covalent Bond

Energy Comparison

CH4
vs.

C–H bond energy Iron melting required

100 kJ/mol 13.8 kJ/mol

Breaking covalent bond in methane molecule requires 7 times higher

energy than melting the iron.
 Added Value of eG layer
❶ Improve coating integrity
Mechanical integrity of coating
(expanded in air)
With eG™
biodegradable coating
3.8-10µm

VS

Another DES
BuMA in the market
eG base layer
200nm

Molecular “velcro-
like” connection
secures adhesion
0.1mm
metal

between the eG layer

and drug coating

*Not to scale Qian J et al. EuroIntervention 2014;10:806-814

Added Value of eG layer
❶ Improve coating integrity

EC can’t cross obstacles taller than 175 microns.

* Simon C et al. J Long-Term effects of Med Impl 2000:10:143-151

 Added Value of eG layer
❷ Reduce heavy metal ion release

• eG™ base layer suppresses corrosion

and ion release from metals (due to
covalent bonding onto the metal
30 316L BMS surface)
25 • Reduce 80-90% heavy metal ions
20
release
ng/cm2
@ 150 days
in 37℃ Saline 15 • Improve the biocompatibility of the metal
(ICPMS)
10
stents and contributes to lower local
inflammation.
5 93 79
% 90
%
0 % eG
™
Coating
Nickel Chromium Molybdemum
Metal
 How long should the drug remain?

• SMC migration peaks at 40 days after stent implantation.

• Drugs not only inhibit restenosis (SMC’s), but
also prevent healing (EC’s)
• The long term residence of drugs slows
down/inhibits re-endothelialization
1 "A paradigm for restenosis based on cell biology: clues for the development of new preventive therapies",
J.S. Forrester et al., J. Am. Coll. Cardiol., 17, 758 (1991).
 Functional Restoration
of
Endothelium within 3 Months
Drug release and arterial drug Time Course for Drug Delivery & Polymer
100 concentration 10 Dissolution
ABSORB…
80 8 ORSIRO…
Drug release %

BIOMATRI…
60 6
FIREHAW…
40 4 ELIXIR…
ABLUMIN…
20 2
SYNERGY…
0 0 BuMABuMA…
(PLGA)
0 20 40 60 80 100 120 140 160 mo
Days after implantation 0 3 6 9 12 15 18 21 24
In Vivo Drug Release Percentage
Arterial Sirolimus Concentration (µg/g) Polymer Drug

• Drug concentration peaks in the artery within 30 days and is below the therapeutic level by 60 days after implantation.
• Timed drug release to prevent SMC proliferation but promote healing with endothelium cell recovery
• Polymer designed to degrade simultaneously with the drug to minimize inflammatory response
 Animal Study1,2:
Better Endothelial Coverage &
Function Restoration
Endothelial coverage % Confocal (CD-31/PECAM-1)
BMS BuMA Cypher
14 days 28 days 90 days

BMS BuMA Cypher BMS BuMA Cypher BMS BuMA Cypher

14
days

28
days

90
days

Result: @90 days:

• near-to-complete (95%) re-endothelialization of BuMA, similar to BMS; Green dots indicate mature ECs
• 80% of Cypher struts are incompletely covered.
Result: @90 days, >75% endothelial
maturation for both BuMA and BMS, better
1 Rabbit iliac study conducted by Renu Virmani in CV Path, US 2007 than 60% of Cypher.
2 Renu Virmani presentation at TCT 2007.

PECAM-1: Platelet endothelial cell adhesion

molecule
Clinical Evidences of BuMA® Stent
 PAND
BuMA A III
BuMA vs. •
RCT
vs. EXCEL
•
PAND OCT • Xience
vs. Xience V •
All comers
1: 1 RCT

PAND A II • vs. EXCEL

•
•
V1:201Pts
OCT
RCT •
•
2350 Pts
TLF @ 1 yr
• 1: 1 RCT • Struts coverage
AI • Regist
• 80 Pts @ 3M
Single-arm
• Struts coverage
•
•
•
vs. Endeavor
224 Pts • ry
2682 Pts
MACE @ 1 yr
@ 3M

• Late loss @ 9M

>5000 Clinical Data

 1
PANDA I
vs. 270 days Late Loss
Margin for non-inferiority: 0.20mm
Endeavor • Prospective, parallel
BuMA Endeavor controlled, multi-center (9)
N=224 0.24±0.33 mm 0.50±0.55 mm study
P=0.0000
• BuMA (n=113) vs. Endeavor
(n=111)
.05 0.1 .15 .20 .25 .30 .35 .40 .45 .50 .55 .60 • PI: Dr. Shu-zheng LV
720 days MACE
Endeavor
Cumulative Incidence (%)

9.91%
Angiography@ 270 +/- 30 days
Results:
37% •Significantly lower Late Loss @ 9
mo of BuMA (0.24mm) compared
BuMA
6.19% with Endeavor (0.50mm)
•Lower MACE rate @ 2 yrs for
BuMA compared with Endeavor
•0 MACE event was observed in
BuMA group after QCA f/u until 2
0 60 120 180 240 300 360 420 480 540 600 660 720 days
years
1 Changfu Liu et al. J South Med Univ 2010;30(5);
PANDA II
Single arm • Prospective, multi-center (58), registry study in China
• Single arm, n=2682
N=2600
• Up to 5 years follow up
• PI: Dr. Yong HUO

MACE(case) @ 12 mo Results @ 12 mo:

• MACE rate 0.82% (22 cases)
8 • Possible In-stent Thrombosis
0.11% (3 cases)

7 7

Cardiac Death TLR AMI

 1,2
PANDA III
vs.
• All comers, prospective, multi-center (48), RCT study
• BuMA (n=1195) vs. Excel (n=1195)
Excel * • PI: Dr. Run-lin GAO
N=2350

Results @ 12 mo:
• No differences were observed for
TLF between BuMA and Excel
group (6.4% vs. 6.4%)
• BuMA was associated with lower
definite/probable stent
thrombosis compared with Excel
stent (0.5% vs. 1.3%, p=0.048)

* JW Medical, China. License

product from Biosensors

1Bo Xu et al JACC VOL. 67. NO. 19, 2016,. 2 Bo Xu presentation at TCT 2015 “Late Breaking Trials”
 1
OCT vs. XIENCE V
vs.
• OCT study by Dr. Bo Yu, 2nd Affiliated Hospital of Harbin Medical University
Xience V
• 20 patients, each randomized overlapped BuMA & XIENCE V at the same lesion,
N=20 same vessel of the same patient.

Struts Coverage (%) @3 mo Struts Coverage (%) @12 mo

100 P=0.653 P<0.001
100 99.2
98
99 98.2
96 95 94.7 98
94 97
92 96
90 95
BUMA XIENCE V BUMA XIENCE V

Result: BuMA has a significantly better struts coverage compared to XIENCE V at 12

months (99.2% vs. 98.2%, P<0.001)

1 Jingbo Hou presentation at EuroPCR 2013 “Late Breaking Trials”

 1 • OCT study by Fuwai Hospital
BuMA OCT
vs. • BuMA (n=33, 16105 struts ) vs. Excel * (n=33, 20493 struts)
• First ever randomised trial to compare early neointimal coverage between two
Excel * ‘similiar’ designed DES.
N=80

Result: significant higher strut

coverage was observed for BuMA
compared with Excel at 3 months.

1 Jie Qian et al. EuroIntervention 2014; 10:806-814

Other Features & Benefits
Superior deliverability Bifurcation favorable

• Bigger cell area

BuMA vs. Firebird 2

5.6mm2 4.37mm2
Lab Testing BuMA vs. XIENCE V

Testing Items Who’s better?

tested by
Stent on Balloon (deliverability) BuMA
Stent flexibility
Stent Alone (conformability) Similar

Push efficiency BuMA 5/9 items favorable to BuMA

2D Track Testing BuMA

Balloon Overhang Similar

Stent Cell Perimeter BuMA

Stent Cell Area XIENCE V

Stent Recoil BuMA

Balloon Deflation Time Similar

Thank you
Kandzari DE et al. www.thelancet.com Published online August 26, 2016 http://dx.doi.org/10.1016/S0140-6736(17)32249-3
Thank you

Lüscher TF et al. Circulation. 2007;115:1051-1058