OrbusNeich Medical K.K. of Tokyo Japan has announced that the Japan Ministry of 
Health, Labour, and Welfare (MHLW) has granted Shonin market approval for the 
COMBO Plus Coronary Stent.  The COMBO Plus Coronary Stent is the first 
drug-eluting stent [DES] to combine the proprietary endothelial progenitor cell 
[EPC] capture technology with an abluminal sirolimus drug elution delivered 
from a biodegradable matrix polymer that achieves full and complete dissipation 
by 90 days.  OrbusNeich's patented immobilized antibody promotes the capture of 
EPCs circulating in the blood to the device surface.  EPCs have been shown to 
promote the formation of a functional endothelial layer that provides 
protection against thrombosis and modulates restenosis. 

The pivotal randomized, multi-center HARMONEE (Harmonized Assessment by 
Randomized, Multi-center Study of OrbusNEich's COMBO StEnt) [NCT02073565] was 
conducted as a global clinical "proof-of-concept" project under the joint Japan 
PMDA-US FDA Harmonization by Doing initiative and the study provided the 
pivotal clinical data used to support the Shonin approval. A total of 572 
patients were enrolled at 50 sites in Japan and the U.S. to support the 
company's application for Shonin approval in Japan and to meet the Pilot trial 
requirements in the U.S.  Patients presenting with ischemic coronary disease 
and non-ST segment myocardial infarction (NSTEMI) were randomized one-to-one to 
treatment with a COMBO Plus Stent or an everolimus-eluting stent (EES) 
comparator. The study's primary endpoint was met in a comparison of clinically 
driven target vessel failure (TVF), defined as cardiac death, target vessel 
myocardial infarction (MI) or ischemia- driven target vessel revascularization 
(TVR) by percutaneous or surgical methods.  The COMBO Plus stent was found to 
be non-inferior in 1-year TVF compared to the EES comparator.  Additionally, 
the COMBO Plus stent was found to have superior healthy stent strut coverage 
compared to the EES control as determined by an independent OCT Core Laboratory 
analysis of serial optical coherence tomography [OCT] imaging at 6- and 
12-months.  (European Heart Journal 2018; 39:2460-2468)

Dr Mitchell Krucoff, Duke University Medical Center, Durham, N.C, USA, and the 
Global Co-Principal Investigator for the HARMONEE trial, stated "The OrbusNeich 
Combo DES with endoluminal biologic endothelial progenitor cell capture 
technology has just become the first coronary device approved for clinical use 
in Japan based on the HARMONEE study which enrolled both Japanese and US human 
subjects in a single prospective randomized trial protocol.  Not only is this a 
huge success for the COMBO DES, but it is also a first-in-kind proof of concept 
for the Japan-USA Harmonization By Doing program (HBD)."

The COMBO Plus stent is designed to address the risk of stent thrombosis 
associated with delayed healing found with conventional DES.  The unique dual 
therapy stent design combines anti-restenotic effectiveness by abluminal 
sirolimus elution from a bioresorbable polymer matrix with pro-healing antibody 
surface coating for enhanced EPC capture from the circulating blood, resulting 
in more complete healing and endothelial functionality.  The COMBO Plus stent 
clinical program now has over 9,500+ subjects included in clinical trials with 
the COMBO stent.  The CE-marked COMBO Plus Dual Therapy stent has claims based 
upon clinical results from this extensive clinical program, including 
indications to allow for flexibility in dual-antiplatelet therapy [DAPT] if 
needed, with a recommended minimum one-month DAPT in stable patients and 
three-months DAPT in acute coronary syndrome [ACS] patients.

"The market approval of the COMBO Plus Coronary Stent in Japan is a tremendous 
achievement for the entire OrbusNeich organization" said David Chien, 
OrbusNeich Medical President and CEO. "A well-coordinated global effort was 
required to obtain the Japan market approval of a unique product such as the 
COMBO Plus Coronary Stent.  We expect this approval to allow OrbusNeich build 
on our strong market position in the Japan percutaneous interventional market."

About the COMBO Plus Coronary Stent 

The COMBO Plus Coronary Stent is the first stent to combine a proprietary 
endothelial progenitor cell [EPC] capture technology on the luminal stent 
surface with an abluminal sirolimus drug elution delivered from a biodegradable 
matrix polymer that is completely dissipated within 90 days. OrbusNeich's 
patented EPC capture technology consists of an immobilized antibody surface 
coating that captures EPCs circulating in the blood to the device surface. 

About OrbusNeich – Pioneers in life-changing technologies 

OrbusNeich is a global pioneer in the provision of life-changing vascular 
solutions and offers an extensive portfolio of products that set industry 
benchmarks in vascular intervention. Current products are the COMBO PLUS 
Coronary Stent, together with stents and balloons marketed under the names of 
AZULE(R), SCOREFLEX(R), SCOREFLEX(R) NC, SAPPHIRE(R) II, SAPPHIRE®(R)II PRO and 
SAPPHIRE(R) II NC, and the TELEPORT(R) microcatheter, as well as products to 
treat peripheral artery disease: the JADE(R) and SCOREFLEX(R) PTA balloons. 
OrbusNeich is headquartered in Hong Kong and has operations in Shenzhen, China; 
Fort Lauderdale, Florida, USA; Hoevelaken, The Netherlands; and Tokyo, Japan. 
OrbusNeich supplies medical devices to physicians in more than 60 countries. 

For more information, visit www.OrbusNeich.com 


SOURCE: OrbusNeich