About Us

History

Founded in 2009, Leeds-based Arterius is developing a next-generation bioresorbable cardiovascular scaffold (stent) with an emerging market-leading clinical profile. The founding directors have significant experience in the development of medical devices and in the cardiovascular devices field in particular. The development team is supported by a consortium of experts comprising, amongst others, clinical advisory team; computational design group at Southampton University; polymer process engineering at Bradford University and pre-clinical and clinical institutions. Arterius has recently completed the pre-clinical trials and, on the back of these, believes that this collaboration has delivered a next generation drug eluting fully biodegradable stent with a market leading profile.

MISSION

Arterius was established by Dr Kadem Al-Lamee and Alistair Taylor to exploit opportunities in the $8.1bn coronary stent market. The company has worked in partnership with a consortium of academic contributors consisting of the Computational Design Group at Southampton University, UK; the Polymer Interdisciplinary Research Centre Bradford University, UK; and the Department of Surface Characterisation and Drug Distribution at Nottingham University, UK to design, manufacture and put into pre-clinical evaluation a family of novel vascular scaffold stents, under the trademarked name ArterioSorb™.

Product Evolution

Coronary artery disease (also known as coronary heart disease or “CHD”) and ischaemic heart disease are caused by a narrowing (stenosis) of the coronary arteries caused by the deposition of atherosclerotic plaque. These deposits limit the blood flow and supply of oxygen to the heart muscle. The stenosis of arteries may be partial or total. CHD may affect one or more arteries and depending on the diameters of the artery (calibres) and degree of stenosis, may be asymptomatic; lead to chest pain (angina); or, in serious cases, cause acute myocardial infarction (heart attack) or death.

TREATMENT

The symptoms and health risks associated with a stenosed artery may be treated medically, by modifying risk factors (for example, smoking, hyperlipidaemia, obesity and hyperglycaemia) and/or by drug treatment (for example, beta-adrenergic blockers, nitrates, calcium-channel blockers, antiplatelet agents and/or statins).

If these medical treatments fail or are inappropriate, two invasive therapies are available: The first, coronary artery bypass grafting (CABG) and involves major cardiac surgery. The second, Percutaneous Coronary Intervention (“PCI”) involves the use of balloon angioplasty to widen an artery from the inside. A balloon catheter is inserted through a femoral artery. When inflated, the balloon increases the calibre of the artery restoring vessel patency and improving blood flow to cardiac muscle. Most PCI procedures involve the use of stents. PCI is a highly effective means of treating acute coronary disease. However medical therapy is often preferable as an initial therapy in patients with stable disease and CABG is more appropriate in patients with highly complex disease, particularly those with diabetes requiring multi-vessel revascularisation.

1970s – PERCUTANEOUS CORONARY INTERVENTION

PCI was first used in 1977 before stents were conceived. However, it subsequently became apparent that while the balloon angioplasty was effective, without some form of post-procedural support, the vessels tended to restenose. This is the result of recoil of the artery which happens when the balloon is deflated, usually immediately or within 24 hours of completing the procedure, and can cause complete blockage of the vessel requiring an emergency CABG. Restenosis of the artery was also seen months after the procedure caused either by continued contraction of the outer layer of the artery (3–6 months after the procedure) or proliferation of smooth muscle cells within the arterial wall (4–6 months after the procedure). As a consequence of these restenoses, rates of acute and chronic vessel occlusion in plain angioplasty were commonly of the order of c.30% to 60% (Contemporary Reviews in Interventional Cardiology (Ref. Delineating the Numerous Causes of Drug-Eluting Stent Restenosis. Vasim Farooq, MBChB, MRCP, Bill D. Gogas, MD and Patrick W. Serruys, MD, PhD)

1980s - INTRODUCTION OF BARE METAL STENT TECHNOLOGIES

In response, the first Bare Metal Stents (BMS) were introduced in 1986 heralding one of the most important advances in the treatment of CHD to date. The first stents comprised tiny expandable metal mesh tubes which were loaded over an angioplasty balloon then inserted into the lumen of the artery during the PCI procedure. When the balloon was inflated, the stent expanded to form a scaffold which held the vessel open, and was left behind after the balloon was deflated and withdrawn.

The advent of bare-metal stents (BMS) largely eliminated the issue of acute and chronic recoil, but introduced new problems in the form of cellular hyperplasia caused by the stent (causing restenosis). The restenosis rates with BMS were reported to be between 16% and 44%, with higher rates of stenosis attributable to several risk factors, in particular, long lesion length and small vessel calibre. Another new problem was stent thrombosis. The physical presence of a stent in the artery interrupted the mechanical flow of blood through the vessel causing blood to clots and potentially life threatening acute occlusions (such as myocardial infarcts).

2000’s - DRUG-ELUTING STENT TECHNOLOGIES

Stent technology (including the design, alloy used and strut thickness) developed rapidly in the 1990s. The second generation products appeared in 2000 in response to the continued concerns over restenosis and thrombosis. These stents comprised a BMS which had been coated in anti-proliferative drugs such as paclitaxel (to prevent tissue growth) or anti-inflammatory/immunosuppressive drugs such as sirolimus, everolimus, tacrolimus or dexamethasone (to reduce the inflammation at the site of the stent). These drugs ‘eluted’ over time providing therapeutic concentrations in local tissues but low systemic doses, thus avoiding systemic adverse effects.

These stents resulted in yet lower restenosis rates; reductions of 50 to 70% when compared to BMS. The uptake of DES was rapid and the market grew at a double digit rate until 2007 when the Cardiology community began to recognise issues with these stents, in the form of late and very late stent thrombosis. It seems that while the DES reduce the incidence of thrombosis in the early period after PCI, pro-thrombotic biologic mechanisms begin to re-emerge once the stents lose their drug coating. Therefore DES can cause coagulation in the bloodstream leading to stent thrombosis many years after stent implantation (late and very late stent thrombosis). This can result in a heart attack, muscle damage and in severe cases result in death. This realization led to a large decrease in sales in 2007.

While these concerns remain, each successive generation of DES has progressively addressed the issue and restenosis rates now sit in the single digits. As a consequence, the majority of PCI procedures are today performed using DES. However there are specific situations where a BMS is preferred and as a consequence there is still a market (c.24%) for BMS.

TODAY - BIORESORBABLE SCAFFOLDS (BRS)

Bioresorbable scaffolds (stents) are made from common biopolymers used in medical devices, such as poly(lactic acid (PLA or PLLA), rather than metal. These stents provide mechanical support for a period of time while the artery recovers from the PCI, before dissolving away to leave nothing behind.

Implantation of the first dissolvable scaffold was described in the 1990s but any potential benefits were eclipsed by the impressive clinical results being achieved with DES stents. Therefore it was not until the late and very late complications of DES became apparent, that the market refocused on scaffolds that could be better conform to the ‘ideal’ clinical profile. There are several potential elements to this profile:

  1. Mechanical Strength: The ideal BRS needs to be formed from a polymer that ensures short to mid-term scaffolding of the vessel in order to maintain patency while the vessel heals and remodels. It is still unclear exactly how long a BRS needs to provide a scaffold before full resorption but currently devices resorb after between 6 and 24 months.
  2. Lower Restenosis: Ideally the scaffold should be drug eluting in order to deliver anti-proliferative drug to the vessel wall and to reduce the incidence of neo-intimal tissue growth that results in reduction of the size of the vessel lumen. The optimum scaffold should be encapsulated into the arterial wall while allowing vessel remodelling.
  3. Lower Early Thrombosis: The scaffold’s physical profile (thickness) should be comparable to (or better than) the available DES in order to avoid any contribution to short term thrombosis.
  4. Lower Late/Very Late Thrombosis: The resorption of the stent should eliminate any long-term risk of thrombosis resulting from the presence of foreign tissue within the vessel.
  5. Ease of Use: The scaffold design must achieve ease of delivery and handling allowing its manipulation through a variety of anatomical locations. The device must be flexible and available in a wide range of sizes and lengths in order to ensure widespread application.
  6. Vascular Remodelling: There is potential to not only match, but to better the clinical profile of the existing products: Uniquely BRSs, offer the possibility of late lumen gain and enhanced vasomotion. These effects have been observed in early clinical studies. Lower incidence of angina at 1 year after PCI with BRS have also been reported when compared to DES (16% vs 28%, p=0.001). This is likely to be due to expansion of the internal elastic membrane and growth of the lumen as the device begins to dissolve and the vessel is constrained.(Serruys PW, Chevalier B, Dudek D, Cequier A, Carrie D, Iniguez A, et al. A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial. Lancet. 2015;385(9962):43-54.)
  1. Repeat Revascularisation: BRS could ease the delicate process of repeat revascularization with PCI or coronary artery bypass grafting, if required. Presently, these procedures are technically difficult with metalwork residing within the fabric of the coronary vessels. This is particularly important in younger patients who are likely to require future intervention.

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