The Development of the Novel BioMime™ Sirolimus-eluting Coronary Stent System
lowering restenosis and target vessel revascularisation (TVR) incidence versus high strut thickness.
The Right Antiproliferative Drug – Sirolimus
The BioMime stent releases the tried and tested sirolimus. In this context, sirolimus is the right candidate for DES application since it targets the ‘final common pathway’ to prevent vascular smooth-muscle-cell proliferation.
The efficacy of SES in animals has long been established and a large volume of published data in human coronaries is available. In a pre-clinical model involving porcine coronary arteries, piglets were randomised to receive either BioMime or NexGen with polymer (control stent) or Cypher (Cordis, US), and arteries were explanted at 28 or 90 days.27
At 28 and 90 days, BioMime-stented segments were as safe as corresponding control stents or Cypher and demonstrated a superiority in reducing neointimal thickness over the control stent or Cypher.27
The
control stent, which was NexGen coated with biodegradable polymer, was found to be equivalent in terms of biocompatibility to the NexGen bare stent, itself suggesting a non-inflammatory nature of the polymer.27
In terms of drug release kinetics, BioMime demonstrated
release kinetics similar to Cypher (see Figure 10).27 The Right Polymer – BioPoly
BioPoly is a biodegradable polymeric base in BioMime comprising a proprietary co-polymer formulation mix consisting of PLLA and PLGA. The principal mode of degradation of BioPoly is via hydrolysis. Degradation precedes diffusion of water into the material, followed by random hydrolysis, fragmentation of the material and, finally, a more extensive hydrolysis accompanied by phagocytosis, diffusion and metabolism. Once hydrolysed, the products are either metabolised or excreted. The lactic acid generated becomes incorporated into the tricarboxylic acid cycle (Kreb’s cycle) and is excreted as carbon dioxide and water. BioPoly has been found to have a short degradation time and has been found to be non-inflammatory in the pre-clinical model. The composition offers a uniform stent coating and does not crack, web, lump or stick to the balloon surface.27
On
BioMime the drug plus BioPoly coating thickness is maintained at 2µm, which is the thinnest among the available DES on the market (see Figure 11).
Achieving Biomimicry Behaviour – Endothelialisation
BioMime in a Pre-clinical Model
In a pre-clinical model, BioMime demonstrated almost 100% endothelialisation at the end of one month, as can be seen in Figure 12. A uniform endothelial coating over and between the struts on edges (close cell configuration) and in mid-segment (open-cell configuration) were observed (see Figure 12).
BioMime Clinical Update
Based on the encouraging pre-clinical results and predictable design configuration, BioMime was studied in a phase IV prospective, single-arm, primary efficacy and safety study involving 30 patients. All patients presented with a single, discrete de novo lesion and were stented with BioMime ranging from 2.5 to 3.5mm and lengths from 13 to 24mm. The primary end-point was MACE, defined as death, myocardial infarction (MI) or any ischaemia-driven target lesion
EUROPEAN CARDIOLOGY 0 13579 11
Time-point (days) 17 19 21 23 25 27
13 15
Figure 11: Scanning Electron Microscopy of BioMime Coating
0.00 0.10 0.20 0.30 0.40 0.50
Mid-stent neointimal thickness (mm) p=0.03
Figure 9: NexGen versus Driver – Neointimal Thickness Figure 7: Complete Endothelialisation in NexGen
Figure 8: Short-taper, Low Balloon Over-hang
0.18±0.08 NexGen
0.30±0.41 Driver Figure 10: Drug Release Kinetics of BioMime 100
20 40 60 80
Before inflation
After inflation 81
Mean drug concentration remaining on stent (%)
mm
EU 1 column = 88mm US 1 column = 90.95mm
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