Download Biofreedom Backgrounder

Background Information on the BioFreedom™
Drug-Coated Stent
BioFreedom represents the latest development in Biosensors stent technology, a radical
departure from current drug-eluting stent (DES) designs. In a DES, the antirestenotic drug is
steadily released over a period of months from a polymer coating on the stent. BioFreedom
is a polymer-free drug-coated stent (DCS) where the drug, Biolimus A9™ (BA9™), is
transferred relatively rapidly - over a period of approximately 50 hours - from the microstructured abluminal (outer) surface of the stent into the vessel wall, leaving only a bare
metal stent behind inside the vessel. The highly lipophilic properties of BA9, a drug
developed by Biosensors specifically for use with stents, facilitates its optimal uptake by the
vessel wall of the target lesion.
Due to these unique characteristics, the inhibition of the restenosis process is comparable
with current DES on the market, without the potential side effects of a polymer.
The BioFreedom FIM Study
BioFreedom FIM is comparing the long-term safety and efficacy of BioFreedom with that of
Boston Scientific’s Taxus™ Liberté™ DES. Two versions of BioFreedom with different doses of
BA9 were used, to assess the optimal dose for clinical use: a standard dose (SD) of 15.6µg
BA9/mm stent length; and a low dose (LD) of 7.8µg BA9/mm stent length.
BioFreedom FIM is a prospective, multi-centre study involving 182 patients with
symptomatic ischemic heart disease, equally randomized into three groups: those treated
with BioFreedom SD; those treated with BioFreedom LD; and those treated with Taxus
Liberté.
All patients have been scheduled for clinical follow-up at 1 month, 4 months, and annually
through to 5 years. The first cohort of 75 patients were prospectively assigned to
angiographic, IVUS and clinical assessment at 4 and 12 months, and the second cohort of
107 patients were prospectively assigned to angiographic, IVUS and clinical assessment at
12 months post-stent implant. It was recommended that all patients received a minimum of
six months dual antiplatelet therapy after stent implantation. The primary endpoint of the
study was in-stent late lumen loss at 12 months in the second cohort. Secondary endpoints
of the study were:



In stent late lumen loss at 4 months in the first cohort
MACE and stent thrombosis rates at 30 days, 4 & 12 months, 2, 3, 4 & 5 years
Clinically-driven TLR, TVR and TVF at 4 & 12 months, 2, 3, 4 & 5 years




In-stent/In-segment binary restenosis at 4 months (first cohort) and 12 months
(second cohort)
In-stent/In-segment minimum lumen diameter (MLD) at 4 months (first and second
cohort) and 12 months (second cohort)
Neointimal hyperplasia volume at 4 months (first and second cohort)and 12 months
(second cohort) measured by IVUS
Biolimus A9 concentrations pre/post procedure at discharge, 30 days and 4 months
Four-month results on the first study cohort, which were reported at TCT in 2009, showed a
significant reduction of in-stent late lumen loss in the two BioFreedom groups (SD and LD)
when compared to the Taxus Liberté group (BioFreedom SD = 0.08mm vs BioFreedom LD =
0.12 mm vs TAXUS Liberté = 0.37mm, p < 0.0001 & p= 0.002 respectively).
Twelve-month data was presented at TCT in 2010. In the second study cohort of 107
patients, in-stent late lumen loss in patients receiving BioFreedom SD was 0.17 mm,
compared with an in-stent late lumen loss of 0.35 mm in the Taxus Liberté group.
BioFreedom SD demonstrated equivalent efficacy, measured by late lumen loss, compared
with Taxus Liberté (P = 0.001), with a trend towards superiority (P = 0.11). In the two
cohorts combined, BioFreedom SD demonstrated sustained safety up to 12 months,
including absence of stent thrombosis.
Two-year data on the overall study population was reported at TCT in 2011, and three-year
data at TCT in 2012.
The three-year results showed similar rates of MACE (a composite of all death, MI,
emergent cardiac artery bypass graft (CABG) and target lesion revascularization (TLR))
between BioFreedom SD and Taxus Liberté (11.9% vs. 10.0%), with no evidence of stent
thrombosis in either group.
LEADERS FREE
Plans for LEADERS FREE were announced at EuroPCR in May 2012.
LEADERS FREE is the world’s first prospective, randomised double-blind trial exclusively
involving patients at high risk of bleeding. The study has been designed to confirm that
BioFreedom is as safe as a bare-metal stent (BMS) in this patient group, and can deliver the
anti-restenotic benefit of a drug-eluting stent (DES), with only a one-month course of DAPT.
The two primary endpoints of the study are:
1. The composite of cardiac death, myocardial infarction and definite/probable stent
thrombosis at one year;
2. The incidence of clinically driven target lesion revascularization at one year.
The study will enrol approximately 2,500 patients identified as having a high risk of bleeding
from 60 sites across Europe, Asia and South America, with planned follow-up for two years.
Patients in both arms of the study are being prescribed only one month of DAPT.
The first patient was enrolled by the study’s Principal Investigator Dr Philip Urban at the
Hôpital de la Tour, Geneva, in December 2012. It is anticipated that the enrollment process
will be completed by early 2014. Primary endpoint data is likely to be presented during
2015.
Regulatory/Commercial Status
BioFreedom received CE Mark approval in January 2013. BioFreedom will be launched in
selected markets during 2013, with a full commercial launch anticipated during 2014.