The Present and Future of Non-Vascular Stents

Transcription

1 The Present and Future of Non-Vascular Stents In our fascination for new-age medical devices such as smart pills and wearable health devices, we do not often pause to think about some of the less-fancy, but equally important medical devices. A class of devices in particular nonvascular s receives much less attention than its 500 million dollar market size demands. At over 5 per cent compounded annual growth, they are a fast-growing market, underscoring their growing importance globally. It would be well worth our time to know a bit more about the device that we could one day end up using personally The human body consists of a network of vessels and ducts that transport fluids necessary for physiological functions across the body. A block in these vessels can obstruct the flow of body fluids, resulting in serious physiological consequences; sometimes even death. It is therefore imperative that the patency of the vessel is maintained, or the crosssection of the vessel is unobstructed by hardening of the walls, calcified deposits, tumours or kinks. Cholesterol and mineral deposits along the inner walls of coronary arteries reduce blood flow through the vessel, a condition known as atherosclerosis. Reduced blood flow to an organ results in the tissues being deprived of oxygen (ischemia), tissue death and depending on the organ which it vascularises heart attack or stroke (brain). Likewise, obstruction of non-blood-carrying vessels such as the gastrointestinal and urinary tracts can have dire and fatal consequences as well. For example, tumours or calcifications can cause obstruction to the urinary tract, hindering the flow of urine through it, resulting in pain, infection, loss in renal function, and in extreme cases, death. Narrowing of the vessel cross-section is known as stenosis or a stricture. Stenosis is most commonly remedied by a minimally-invasive corrective procedure involving a device known as a. A is an implantable medical device that is used to maintain the patency of stenotic vessels. Stents are usually tubular in shape; they are inserted into blocked vessels in order to push out the narrowing walls and to restore an unhindered cross-section for fluid transport. Depending on the type of vessel they are used in, they are classified as vascular and non-vascular s. Non-vascular Stents Non-vascular s are a family of devices for a variety of applications, including biliary, oesophageal, colonic, bronchial and tracheal implantations. The use of non-vascular s in these applications is fuelled by a number of market drivers. Key among them is the benefit offered by the device and its way of implantation. Stents employ a minimally-invasive procedure for implantation, which is in contrast to an open surgical procedure that surgical treatment procedures require. A minimally-invasive procedure also ensures lesser pain; faster recovery period and a shorter hospital stay (and hence, lower medical bills). Non-vascular s find increasing application in gastrointestinal, urological and pulmonary diseases, owing to an 56 INTERNATIONAL PHARMACEUTICAL INDUSTRY Summer 2015 Volume 7 Issue 2

2 Clinical Research ageing population, changing lifestyle habits and environmental conditions. Besides these, ophthalmic and neural applications are fast-emerging as important non-vascular applications. A large addressable market underscores the importance of and the growing need for non-vascular s. Large medical device companies such as Boston Corp., Covidien Ltd., and C. R. Bard, Inc. have recognised this market need, and developed a portfolio of non-vascular products. Gastrointestinal: The family of gastrointestinal (GI) s includes biliary, duodenal, trans-hepatic, oesophageal and pancreatic s. Globally, there is an acknowledged increase in the incidence of GI diseases. In 2014, the United European Gastroenterology Society, a not-for-profit professional society of digestive health professionals, conducted a survey on the changing trends in GI disorders. The pan-european survey, covering 28 European countries, revealed a marked increase in conditions such as upper GI bleeding, inflammatory bowel disease, colorectal cancer and many other diseases, particularly among the elderly. The American Cancer Society estimates approximately 93,000 new cases of colon cancer and nearly 40,000 new cases of rectal cancer are diagnosed in the US every year. These new cases are in addition to the millions already suffering from colorectal cancer. Surveys conducted by the National Institutes of Health estimate that at least 10-15% of adults in the US suffer from gallstones in the biliary tract. These conditions and others such as bile duct injury, oesophageal perforations, and gallstones require non-vascular ing either as a remedial procedure, or as a supplementary procedure. Urological: Obstructions in the ureter necessitate ing procedures to alleviate the blockage or provide a shunt for fluid drainage. Ureteral s are commonly used to alleviate obstruction in cases of nephrolithiasis (kidney stones), tumours, strictures, or retroperitoneal fibrosis. Stents are also used in cases of prostatic obstructions or due to a complication of prostatectomy. The American Urological Foundation estimates that approximately 15 million Americans suffer from urinary incontinence (accidental loss of urine) and between 25 and 30% of American adults suffer from obstructive uropathy (blockage of urine). In such cases, particularly in cases of blockages, a ureteral (also known as or ureteric ) is inserted into the ureter to bypass the blockage and enable urine flow from the kidneys. A ureteral varies in diameter and length, with some s as long as 12 inches. These s are often temporary s, intended to provide relief from pain and difficulty in passing urine. Pulmonary: Pulmonary or airway s are designed to keep the tubular structures in the pulmonary system (trachea-bronchial tree) open. Globally, there is a growing patient pool with airway obstruction along with the number of pulmonary surgical Companies all around the world challenge us every day to create new products tailored to their needs. We embrace these challenges. We are engaged with AGILITY. FLEXIBILITY. PERFORMANCE. EMPATHY. INTERNATIONAL PHARMACEUTICAL PRODUCTS MANUFACTURED IN PORTUGAL INDUSTRY 57 STEAM TRAPS REDUCING VALVES CONTROL VALVES HEAT EXCHANGERS Zona Industrial da Guia Pav Brejo Guia PBL Portugal adca@valsteam.pt

3 Design Considerations Coil geometry Woven or braided design Anti-migratory design Antimigration collar (with rings) Anti-reflux designs with valves Stent coating Stent covering Uses Pros: Flexible and easily retrievable Cons: Limited strength Used in self-expanding structures. Knitted Nitinol used in tracheo-bronchial s as it can change its shape according to the contours of the airway as well as can exert pressure against acute compression forces The designs are to prevent migration due to the peristaltic movement of the gastrointestinal tract or the urinary tract The gastrointestinal s are designed to decrease the risk of reflux and aspiration of the gastric juice Hydrophilic coating which results in low friction, high ring stability and low tendency of encrustation. Antibiotic-coated s prevents infection Stents are covered with silicone or polyurethane to prevent tumour ingrowth and reduce food impaction Tabular column 1: Non-Vascular Stents Design Innovations interventions. Conditions such as central airway obstruction, chronic obstructive pulmonary disease (COPD) and asthma necessitate the use of airway s, to open up narrowed airways and ease the burden of respiration. The National Heart, Lung, and Blood Institute estimates over 23 million Americans currently suffer from asthma. Global health surveys peg this number around 350 million, with another 300 million suffering from COPD. Healthcare databases record that more than 500,000 procedures of bronchoscopy are performed annually in the US, showing the prevalence of pulmonary surgical intervention. The trachea-bronchial obstructions requiring pulmonary s include complications relating to lung cancer, respiratory infection, tuberculosis, and so on. Examples Esophacoil by EV3 Corporation Silhouette Ureteral Stents by Applied Medical with coil-reinforced technology Wallflex by Boston Ultraflex tracheo-bronchial by Boston HV Stent Plus and SX-ELLA Stent Esophageal HV by ELLA-CS are equipped with a unique anti-migration collar. Tracheal Stents with Posts or Rings by Hood Laboratories. ALIMAXX-ES Esophageal Stent by Merit MedicaEndotek has anti-migration struts Hanaro by M.I.Tech with large flare ends for anti-migration effect Esophageal Flexella plus by ELLA-CS has a special anti-reflux valve. Esophageal Z-Stent by Cook Medical has a unique windsock design with Dua Anti- Reflux Valve Hanaro and Choo by M.I.Tech, with anti-reflux esophagus valve istent - Teutaflex Ureteral Stent by Hospital Innovations Percuflex Stent with HydroPlus Coating by Boston INLAY OPTIMA ureteral by BARD Medical with phreecoat to stabilize the PH. Triclosan eluting s Triumph by Boston Permalume covered WallFlex Esophageal Stents by Boston. ATRIUM ICAST balloon expandable covered tracheobronchial Key properties of the materials used in the non-vascular are biocompatibility, resistance to corrosion, flexibility, expandability, and high strength. Some of the materials used to develop s are given in the table below: Depending on the nature of the blockage, pulmonary s are either Y-shaped (to prop-up narrowed airway bifurcation), or are tubular in shape for relieving blockages further down the pulmonary system. Factors such as smoking and global environmental factors such as air pollution and exposure to inflammatory chemicals, particularly in developing countries, are expected to increase the market need for airway s. Innovations in Design and Materials Non-vascular s vary greatly in size specifications, materials and design. Depending on the nature of the, the length could be as much as 18cm (typically gastrointestinal or urological s) or as low as microns in length (known as micro-s, used in ophthalmic applications). Tabular Column 1 highlights a few design characteristics for different applications. Biodegradable Polymers: The use of biodegradable polymers such as poly acryl amine, poly lactic acid-glycolic acid, poly capro-lactone and others, in non-vascular s, are recent material innovations. Biodegradable materials present the advantage of biocompatibility and eliminate the necessity of removal. The either degrades over time or gets assimilated into the body (bio-resorbable materials). Esophageal s manufacturer ELLA-CS (Czech Republic) uses polydioxanone, a material used to manufacture sutures, in their oesophageal s. Boston uses poly lactic acid for its bio-absorbable biliary wall s. Self-Expanding Stents: In order to reach particularly narrowed vessels, self-expanding plastic s (SEPS) and self-expanding metallic s (SEMS) are used. These s are present in deflated or collapsed state, so that they can pass through narrowed structures and they are expanded upon reaching the site of implantation. They find application as palliative or assistive devices during advanced stages of gastrointestinal cancer. These are some of the innovations that non-vascular s have benefitted from in the last few years. Already device manufacturers are taking cues from coronary devices, which have a longer track record of innovation and market acceptance. Design improvements such as heparin-coating of s to prevent blood coagulation, anti-microbial coating to prevent infection and addition of anti-restenotic drugs to the s, are some of the design innovations already in development stages. Emerging Application Areas Ophthalmic and neural applications of non-vascular s are among the new and niche markets that have opened up in the last few years. Both application areas eyes and the brain are sensitive areas for implantation of devices. They also necessitate a much smaller device (in the order of microns, or micrometres), known as a micro-. In most cases, these s do not so much perform the role of opening up blocked vessels, as they act as the vessels themselves. In other words, the s act as shunts for relieving an organ or a part of the organ from pressure due to fluid build-up. INTERNATIONAL PHARMACEUTICAL INDUSTRY 58

4 Materials Pros and Cons Key Players Silicone Pros: Non-adherent, highly flexible, and has shape memory; easy to insert and remove. Cons: Less strength, migration Dumon s by Novatech Mini Monoka silicone monocanalicular lacrimal s by FCI Ophthalmics Mono Stent monocanalicular by Eagle Vision Inc. Nitinol Pros: Super-elasticity and shape memory, highly biocompatible, flexible, has excellent shape memory and is corrosion-resistant, MRI-compatible Cons: Tissue trauma by metals Ultraflex tracheobronchial by Boston Niti-S Enteral Colonic by Taewoong Medical Nitinella Plus biliary by ELLA CS Stainless steel Cobalt-chromium alloys Pros: High strength, flexibility, cost-effective Cons: Not biocompatible, MRI incompatible, cause restenosis and thrombosis Pros: Super-elasticity, shape memory, MRI-compatible, corrosion-resistant, biocompatible Cons: Tissue trauma by metals Omnilink.035 Biliary Stent System by Abbott Vascular Visi-Pro Balloon-Expandable Biliary Stent System by Covidien Resonance ureteral by Cook Medical Tabular column 2: Non-Vascular Stent Material Innovations Ophthalmic: Glaucoma is a group of eye disorders that are caused due to an increase in the intraocular pressure (IOP), or the pressure due to fluid build-up in the eye. The Glaucoma Research Foundation lists glaucoma as the leading cause of blindness in the world. An estimated 2.2 million Americans and tens of millions more worldwide, have glaucoma. There is no cure for glaucoma as of now, but the use of a micro- to reduce the IOP, so that the optic nerve is not damaged, is an approach that is most commonly resorted to. At a maximum length of 1 millimetre and weighing a few micrograms, ocular s are fast becoming a preferred glaucoma management option. Ophthalmic s are also surgical options for diseases like monocanalicular trauma and for structurally correcting the irideocorneal angle. Neural: With the increasingly ageing and obese population, the pool of ischemic and haemorrhagic stroke patients is also increasing. The United States Centers for Disease Control and Prevention lists stroke as the third leading cause of death, killing more 140,000 people each year. While there are a number of reasons for a stroke to occur, a sizeable number around 40,000 to 60,000 incidences per year in the US alone are due to intracranial cerebral atherosclerosis. Similar to the plaque build-up in coronary arteries, there is protein, cholesterol and mineral accumulation along the vessels in the brain, resulting in narrowed ducts. When primary options such as blood thinner medications and anti-coagulants do not effectively work, ing becomes a vital go-to option. There is an increasing demand for minimally-invasive surgical procedures to treat these patients. Micron-sized neural s, such as those developed by Stryker Corporation, are used as implants to treat brain aneurysm and intracranial stenosis. The different types of non-vascular s that have received approval for clinical use, or are currently in the process, are listed in Tabular Column 3. The Road Ahead The global non-vascular market landscape is a mix of large and small companies, those with varied product focus and others with focus exclusively on non-vascular products. On one hand are medical device giants such as Boston Corp., Cook Medical, Inc. and Covidien, Ltd. In addition to being important players in the nonvascular market, these companies also have a substantial global presence in coronary and peripheral s. On the other hand, companies such as ELLA-CS, s.r.o and South Korea-based Taewoong Medical Co., Ltd. focus exclusively on gastrointestinal s. There are also single-product start-up companies such as Ivantis Medical, Aquesys and Transcend Medical (all based in California), material and pharmaceutical companies that play a crucial role in market innovations. The growing importance of nonvascular s has been illustrated with a snapshot of the total addressable market, key growth drivers, recent innovations in product design and new application areas. In addition to these, the possibilities of partnerships, strategic alliances and business partnerships make the nonvascular market an exciting space to watch out for in the coming years. 60 INTERNATIONAL PHARMACEUTICAL INDUSTRY Summer 2015 Volume 7 Issue 2

5 Product name Application Area Product Status Importance XEN 45 gel (Aquesys, Inc.) World s first minimally invasive subconjunctival for the treatment of glaucoma Met the completion of enrolment in the US clinical trial Receives Class 3 Medical Device License from Health Canada This 12-month, multicentre singlearm study data will facilitate the US FDA approval for this. This is an important milestone for obtaining US market clearance. With commercialisation existing in Europe, this approval expands Aquesys s footprint into another large market of Canada. InnFocus micro shunt (InnFocus) Ocular for the reduction in intra-ocular pressure. This patented micro- showed good results. It showed 80% reduction in eye-drop medication use-- over 70% off medications completely at 3 years Company believes that these positive results will convince the surgeons to use the MicroShunt for treatment of glaucoma. AEROmini Tracheobronchial (Merit Medical) It is indicated for use in the treatment of tracheobronchial strictures produced by malignant neoplasms. U.S. Food and Drug Administration approval under section 510(k) The approval is expected to boost the growth of Merit Medical System, Inc. WallFlex biliary (Boston ) Biliary for the palliative treatment of biliary strictures produced by malignant neoplasms. Positive results in the trial showing the effectiveness and safety of fully covered self-expanding metal s in the treatment of biliary obstruction in benign bile duct strictures patients. The positive result substantiates the US FDA and CE mark approval. It showcases the strong presence of Boston in the gastrointestinal market. WallFlex esophageal (Boston ) Fully-covered is used for treatment of refractory benign esophageal strictures. Has received the CE mark approval in Europe. The commercial availability of WallFlex in the European market promises revenue growth for Boston. Evolution oesophageal (Cook Medical) This is indicated for obstruction that is caused by malignant or benign oesophageal stricture. Cook Medical initiates the first multicentre US study to evaluate the possibility of removing a self-expanding metal after malignant and benign strictures have been treated. If this study shows the possibility of safely removing metal s, it can widen the medical options for different varieties of patients and can increase their potential patient market. Evolution Biliary (Cook Medical) Indicated to relieve symptoms associated with obstruction of the bile duct. US FDA has granted 510(k) clearance. With a CE mark already granted in Europe, this approval will expand its market into the United States. Debarati Sengupta is a Research Analyst working with the Technical Insights Healthcare division of Frost & Sullivan, a growth partnership services company. Debarati graduated with the first class Master s degree in pharmacy (pharmaceutical chemistry) from Birla Institute of Technology. She has industry expertise in competitive intelligence and healthcare market research. She has an experience base covering sectors like pharmaceutical, biotechnology and medical devices. debaratis@ frost.com Bhargav Rajan is a Research Analyst working with the Healthcare Division of Technical Insights, Frost & Sullivan. He tracks innovations in medical devices, medical imaging, clinical diagnostics and healthcare practices. Bhargav holds a Master s degree in Biomedical Engineering from the University of Florida, Gainesville, and has academic and industry experience in regenerative medicine and tissue engineering. He can be reached at bhargavr@frost.com. INTERNATIONAL PHARMACEUTICAL INDUSTRY 61