Surgical sealants and fibrin glues are biologically-based products designed to aid in the process of clot formation. Clotting is the first naturally occurring process in wound repair, and affects many subsequent biochemical processes in the wound healing cascade.
During the wounding event, blood from capillaries at the damaged tissue site seeps out and reacts with tissue proteins and air to cause platelets and complement factors to trigger the cleavage of pro-thrombin into thrombin which then changes fibrinogen into fibrin, the main insoluble component of a blood clot.
It was natural for practitioners, looking for effective haemostasis, to look at fibrin as a source of effective haemostatic activity. In the 19th century, physicians used fibrin powder to stop bleeding. During the period from 1940 to 1960, understanding of blood fractionation and the development of processes for preparing blood fractions, meant that a pure form of fibrin could be prepared and manufactured in a stable format.
Fibrin sealants represent the most useful of surgical hemostats. These products can be used to clot blood but are also used to seal around suture lines for organ transplants, mastectomies, and various resection procedures, to prevent leakage of fluids and gases. A number of companies have developed devices capable of preparing autologous fibrin and platelet formulations that can be used as sealants, and active mixes of growth factors to aid repair. Harvest Technologies, Plasmaseal, Thermogenesis, Biocoral Inc, and Interpore Cross Medical (Autologous Growth Factors product) are four companies with products designed to address this need.
Because sealants are often available as multicomponent systems that need to be mixed immediately prior to surgical application, several innovative devices have been developed to facilitate application. During product manufacture, the thrombin component and the Factor XIII/fibrinogen components are kept separate until required. Addition of fibrin product to a bleeding surface primed with the other component results in accelerated hemostasis and a sealing effect on the bleeding surface.
(From “Worldwide Surgical Sealants, Glues and Wound Closure Market, 2007-2011.” Published February 2007, MedMarket Diligence, LLC. For more information see report description, table of contents.)
(The GERD patient population is a largely untapped surgical market; see chart entitled, “Total Potential Market for Endoscopic GERD Therapies”)
Physicians from UT Southwestern Medical Center and engineers from UT Arlington have collaborated to develop a new technology for detecting the occurrence of heartburn and gastroesophageal reflux disease (GERD). Presented in May at the Digestive Disease Week conference in Washington, DC, the new system involves the use of a small chip designed to replace current standard testing procedures, which can cause patient discomfort and impact normal eating habits.
The new wireless system uses radio frequency identification technology (RFID), which is being utilized in many industries for tracking inventory. To create the new device, RFID technology was paired with impedance monitoring.
To monitor the esophageal environment, a small, flexible RFID chip is pinned to the esophagus. The chip utilizes a special plastic material intended to prevent patients from feeling it in their throats. Measuring roughly two square centimeters, the device monitors electrical impulses of liquids moving through the esophagus, and whether they are acidic or nonacidic. The chip collects the data and sends it to a wireless receiver worn around the neck. As patients go about their normal daily lives, the chip will monitor the presence of acid, gas, or water, after which physicians review the data to determine if the patientâ€™s heartburn symptoms coincide with eating a meal or other activities.
Researchers have tested the device in the lab to ensure it accurately identifies the acidity of substances and can send results through human tissue. The next step will involve testing in animal models. It has taken roughly two years to develop the wireless RFID system and enable it to detect and send data. The receiver will include a button that the patient can push when they begin eating. Eventually, the engineers hope to design a device similar to a PDA to store the collected data. This would then be downloaded for analysis at the doctorâ€™s office.
New monitoring methods for GERD are sorely needed to replace current methods, which require placing a flexible catheter tube through the nose and down into the esophagus. The procedure is very uncomfortable and, because the presence of the catheter usually necessitates a change in the way a patient would normally eat and drink, it can produce biased test results. Since no catheter is required with the RFID system, doctors are hopeful that it will make it easier for patients to eat and drink as they would normally and maintain their usual activity levels.
Several other technologies have been developed in recent years that provide a noninvasive alternative for gastrointestinal diseases. These include the PillCam, a small pill-sized wireless camera that snaps photos during its journey through the digestive tract, and the Bravo capsule, another wireless system that detects esophageal acids. Both of these are both also used by UT Southwestern gastroenterologists.
GERD can occur in adults, children and infants; as many as 10% of Americans experience heartburn on a daily basis, and it is estimated that GERD affects 25%â€“35% of the population. Current diagnostic methods include barium swallow, endoscopic manometry, and pH testing. Treatments include lifestyle modification, antacids, proton pump inhibitors, positional therapy and surgery. Complications of GERD are common, including esophagitis and Barrettâ€™s esophagus, a potentially precancerous stage of disease.
Exhibit ES-8:Â Selected Sealant Product Companies and Their Strategies
Products and Prices
Focal division of Genzyme
Seal L $30 per ml
Available for lung resections in Europe and as an adjunct for non-hemostasis
sealing in the USA. Focal exploiting light activated hydrogel IP. Focal is strategically focused on exploiting unique sealant
capability of its products in neurological, cardiovascular,
gastrointestinal, and thoracic applications.
(Dynastat) $50 per ml
A sprayable liquid hemostat adjunct for use in surgical procedures to
control bleeding in specific clinical applications. Five year
agreement with Tyco for a broad range of indications in the USA,
Europe, Latin America, Middle East, Australia, New Zealand, and India. Cohesion provides unique products for sealing and hemostasis
targeted at the full range of surgical procedures.
Medical Acquired by Baxter
$28 per ml
Non-sealant hemostat for all hemostasis as an adjunct, including problematic
bleeding. Strategy is to develop patented products which combine
technologies incorporating a number of processed mammalian
biomaterials and have hemostatic benefits for surgery in demanding
actively bleeding procedures, and lead to rehabilitation and
re-operation benefits by reducing adhesion formation.
$65 per ml
Homologous pooled fibrin, human thrombin, and bovine aprotinin. Adjunct for
hemostasis in an expanding range of indications. Baxter focuses on
biopharmaceuticals, vaccines, biosurgery and transfusion products and
provides products for medication delivery and dialysis. The bioscience
division of Baxter provides innovative solutions for biosurgery,
tissue regeneration and surgical hemostasis.
$45 per ml
Haemostatic adjunct for aortic dissection during surgery and may also be used
during lung procedures; contains proprietary mixture of bovine albumin
and glutaraldehyde. CryoLife focuses on providing donated human
tissue for surgical procedures. Recently has focused on developing
synthetic and engineered products as replacements for donated tissue.
CryoLife will continue to target Bioglue at procedures which require a
strong hemostatic tissue sealant, and compete on product benefits with
$65 per ml
Hemostat adjunct identical to Tisseel. Strategy to become a fully
integrated supplier of haemostatic and sealant products and to evolve
these into new uses such as drug delivery.
Source: MedMarket Diligence, LLC
From “Worldwide Surgical Sealants, Glues and Wound Closure Market, 2007-2011,” published February 2007. Click for details.
This report details the complete range of sealants & glues technologies used in traumatic, surgical and other wound closure, from tapes, sutures and staples to hemostats, fibrin sealants/glues and medical adhesives. The report examines the clinical and technology developments underlying this huge and rapidly growing worldwide market, with data on products in development and on the market; market size and forecast;Â competitor market shares; competitor profiles; and market opportunity.This report is a market and technology assessment and forecast of products in wound closure. The report details the current and emerging products, technologies and markets involved in wound closure and sealing using sutures and staples, tapes, hemostats, fibrin and sealant products and medical adhesives. The report provides a worldwide current and annual forecast to 2011 of the markets for these technologies, with particular emphasis on the market impact of new technologies through the coming decade. The report provides specific forecasts and shares of the worldwide market by segment for the U.S., Europe (United Kingdom, German, France, Italy, BeNeLux), Latin America, Japan and Rest of World.
The report provides background data on the surgical, disease and traumatic wound patient populations targeted by current technologies and those under development, and the current clinical practices in the management of these patients, including the dynamics among the various clinical specialties or subspecialties vying for patient population and facilitating or limiting the growth of technologies. The report establishes the current worldwide market size for major technology segments as a baseline for and projecting growth in the market over a ten-year forecast. The report also assesses and projects the composition of the market as technologies gain or lose relative market performance over this period.
* * * See the December 2015 report, “Global Market Opportunities in Peripheral Arterial and Venous Stents, Forecast 2020”. A $500 advance discount is available until publication. details * * *
[From published research by MedMarket Diligence, April 2007]The market for drug-eluting stents has yet to recover completely from controversies first voiced in 2006 related to device safety. As a result, while the leading manufacturers are working to regain lost market share, the door has been opened for new devices (such as biodegradable stents) to enter the market, devices that can address the safety issues while producing outcomes that still surpass those of bare metal stents.In 2006, reports began to hit the U.S. market that drug-eluting stents (DESs) might pose an increased risk of late stent thrombosis for some patients (see MedMarkets, [subscribers only] “Drug-Eluting Stents Vie for Market Share With Innovation, Acquisitions,” October 2006). Combined with manufacturing issues, both Johnson & Johnson/ Cordis and Boston Scientific (the only two competitors in the U.S. market) saw significant drops in sales by year-end.
Earlier in 2006, physicians were using DES devices in roughly 90% of all stent implants. By the beginning of 2007, physicians were opting to use DESs in only 75% of cases, opting instead for bare metal stents. With some studies showing that usage of DESs result in positive outcomes when paired with an anti-restenotic drug such as Plavix, physicians have become reluctant to risk using a DES if the patient is not likely to use the medication due to cost or noncompliance.As a result, many are speculating that the market for DESs has reached a plateau. Optimistically, the DES share of the stent market might grow back to 85%, but given the anticipated entry of new competitors (Abbott Vascular, Medtronic Vascular, and others) into the market, it is vital for leading manufacturers to develop next-generation products as quickly as possible. In fact, beginning in late 2007, the introduction of new generation products and new technologies will spur the market to halt its current downturn and begin growing again, albeit at a modest rate (see chart above, “Worldwide Market for Drug-Eluting Stents”). Market competitors are shown in the chart below, “Developers of Cardiovascular Drug-Eluting Stents.”
FDA Responds to Market Pressure
In response to the previously mentioned study results questioning the safety of DESs, the FDA’s Circulatory System Devices Panel met in December 2006 to review safety data. According to a statement posted in January, the FDA panel did confirm a slight increase in stent thrombosis for the Cypher and Taxus stents when compared to bare metal stents within one year after implantation. However, the panel also found that this increased risk of thrombosis did not result in an increased risk of death or myocardial infarction when compared to bare metal stents. In studies examined by the FDA panel, DESs were not associated with an increased rate of all-cause mortality when the devices were used as approved. All told, the FDA panel stated that larger, longer-term studies are necessary. In addition, the agency is to consider requiring up to five years of post-approval studies for DESs.
Medicare Responds to Cost
In 2002, Medicare approved payment coverage of DES. This is unique in that the Medicare approval came prior to the FDA approval, which usually is not the case. However, in light of the FDA panel recommendations, Medicare may reconsider its coverage of DES. At the least, the agency may limit coverage to FDA-approved indications. In 2005, Medicare paid roughly $14.7 billion for DES surgeries.
The COURAGE Trial Controversy
In late March at the annual meeting of the American College of Cardiology (ACC), researchers presented controversial results from the COURAGE study, stating, “in patients with stable coronary artery disease, percutaneous coronary intervention (PCI) did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy.” The COURAGE study compared “optimal medical therapy” (i.e., lifestyle intervention and intensive pharmacological therapy using cholesterol-lowering statins, blood pressure drugs and aspirin) to a combination of “optimal medical therapy” and PCI (i.e., angioplasty and primarily bare metal stents but also some DES). Because the study covers more than four years, the majority of stents used were bare metal. Regardless, even though DESs are simply too new to have played much of a role in the study, the DES market was directly impacted by it. Most clinicians agree that outcomes in stent patients are greatly improved when the patient maintains a regimen of an anti-clotting drug such as aspirin or Plavix for at least one year after stent implantation. The problem with the study is that patients with stable coronary disease are not typically recommended for stent therapy. In additional, the “optimal medical therapy” used in the study was more aggressive than what would be typically prescribed in everyday practice. Nonetheless, the manner in which the results were presented (and reported on by the media) did not put stents in the best light. The good news is that U.S. health insurers don’t seem to be overly concerned with the COURAGE study results. Several big insurers (including Aetna and Blue Cross Blue Shield) recognize that the issues surrounding stent implantation go beyond the endpoints of the COURAGE study. The COURAGE study was sponsored by the U.S. Department of Veterans Affairs, the Canadian Institutes of Health Research and several pharmaceutical companies, including Merck, Pfizer and Sanofi-Aventis.
Durables Remain the Standard
In spite of the controversy, standard DESs (which elute an active drug and stay behind to keep the vessel propped open) are still used in the majority of stent implantations. Although Boston Scientific was the second company behind Cordis to market a DES, the former is the current market leader with its Taxus Express2 stent and the upcoming Taxus Liberté next-generation device. Unfortunately, Boston Scientific was unable to launch the Taxus Liberté as planned in late 2006 due to a warning letter it received from the FDA in regard to unrelated issues. As a result, the FDA will not grant marketing approval for the Taxus Liberté until the issues are resolved. Meanwhile, the device is available internationally in all areas except the United States and Japan. In April 2007, Boston Scientific announced that it did receive Japanese marketing approval earlier than anticipated for the Taxus Express2 stent. The company will launch the device in the $500 million market Japanese market once it gains reimbursement approval as well. Another bit of good news Boston Scientific obtained this year was in January when the FDA extended the shelf-life for Taxus Express2 from 12 months to 18 months. The shelf-life is already set at 18 months internationally. Boston Scientific is also moving ahead with a new device, the Promus stent, which is scheduled to hit the U.S. market in 2008. Developed by Guidant under the Xience name, the everolimus-eluting stent was folded into the Abbott portfolio when Guidant was acquired. Abbott has granted Boston Scientific distribution rights in the United States, where Boston Scientific will market the stent under the Promus name. Abbott has retained international distribution rights for the Xience, which it launched in Europe in January 2007. Xience holds an advantage over other DESs in that it is thinner and more flexible than many others. With struts that are roughly one-half the size of Cordis’ Cypher stent, the Xience presents less risk of clotting than other stents might. Meanwhile, Johnson & Johnson is attempting to regain market superiority with its Cordis Cypher stent. J&J and Boston Scientific are currently tussling in court in regard to DES patent infringement issues. Boston Scientific had previously prevailed in lower courts in disputes related to the stent itself and the polymer that binds the drug to the stent. However, in mid-April, a U.S. federal court ruled that J&J does not infringe on the patent. The end of this story is not yet in sight; Boston Scientific vows to consider all options available. In November 2006, the lead investigator of the ARTS II study, Patrick Serruys, MD, PhD (Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands), presented data related to Cordis’ sirolimus-eluting Cypher stent. The preliminary data showed that Cypher may provide a viable alternative to surgery in patients with lesions in two or more vessels. After three years, patients showed a MACE rate for Cypher that at 80.2% was statistically similar to CABG surgery (83.9%). When compared to bare metal stents, Cypher passed with flying colors as the MACE rate for bare metal was 65.3%. In regard to severe events (death, stroke or heart attack), 91.6% of Cypher patients did not experience a significant event, compared to 89.0% of CABG patients and 86.7% of bare-metal stent patients. ARTS II includes 607 patients from 45 European centers. While Cordis’ next-generation Cypher Elite stent is scheduled to begin U.S. clinical trials later this year, the company recently completed its $1.4 billion acquisition of DES developer Conor Medsystems. Conor’s first-generation paclitaxel-eluting CoStar received CE Mark in February 2006 and expects a U.S. launch in late 2007 or 2008. The second-generation CoStar II device is currently in clinical trials. The company is also developing the pimecrolimus-eluting Corio and the SymBio, the latter of which elutes both pimecrolimus and paclitaxel. Medtronic Vascular’s Endeavor stent is following hard after the market leaders. Its Endeavor zotarolimus-eluting stent received CE Mark in July 2005 and anticipates a U.S. approval later this year. In safety trials, Endeavor showed an overall thrombosis rate of 0.3% with no stent thrombosis beyond 30 days. In October 2006, preliminary data were presented at the TCT 2006 annual meeting on the company’s next-generation Endeavor Resolute stent. The first-in-man RESOLUTE trial showed the zotarolimus stent resulted in a MACE rate of 3.8% with no target lesion revascularization and no stent thrombosis. The trial followed 130 patients at 12 centers in Australia and New Zealand. The Endeavor Resolute incorporates the proprietary BioLinx polymer system, which is designed to accomplish extended release of drugs and is compatible with multiple drug platforms. In a head-to-head comparison, Endeavor and Endeavor Resolute showed equal rates of biocompatibility at 28, 90 and 180 days. MIV Therapeutics (MIVT) jumped fully into the DES fray in February 2007 when it completed its acquisition of India-based Biosync Scientific, developer of (among other products) stainless steel and cobalt chromium stents, both of which have already obtained CE Mark. MIVT intends to apply its proprietary coatings to Biosync’s bare metal stents to create a new polymer-free DES—the Smart stent. MIVT’s stainless steel Smart stent will be capable of eluting midastaurin, sirolimus or zoledronic acid. In porcine studies, MIVT’s polymer-free hydroxyapatite coating fared well when compared to Cordis’ Cypher stent, producing outcomes that were just as good or better than the latter. MIVT plans to begin first-in-man studies early this year. MIVT is also developing a nanofilm coating with sufficient capacity to carry adequate amounts of anti-inflammatory drugs. Still pending is MIVT’s planned acquisition of China-based Vascore Medical, announced in September 2006. Like Biosync’s stents, Vascore’s bare metal stents would also provide a suitable platform for MIVT’s biocompatible coatings. In March 2007, shares of Xtent gained 5.7% when investors caught news of good prospects predicted for the company’s Custom NX DES. Xtent’s DES can be customized for use in single, long and multiple lesions in a variety of lengths and diameters. The company intends to make its DES less expensive than other manufacturers’ stents by setting a single per-procedure price. The Custom NX uses Biosensors International’s Biolimus A9 coating, which is still awaiting FDA approval. Custom NX is currently in European clinical trials with a launch there anticipated in 2008 and a launch in the United States in 2010. In December 2006, CorNova announced that its cobalt-chromium Valecor stent received the CE Mark. Valecor will be used in the development of a new DES, which will incorporate CardioTech International’s custom-formulated ChronoFlex polymer. Valecor’s structure is characterized by its thin strut size. CardioMind is developing its Sparrow DES for small vessels. The Sparrow is coated with sirolimus in a biodegradable polymer matrix. The device is placed with a 0.014” guidewire platform. In porcine studies, the results of which were presented at CRT 2007 in March, safety was demonstrated with low intimal thickness, favorable lumen area, and minimal inflammation and foreign body response. In addition, a study of overlapping stents (minimum of 4 mm) showed no strut fractures at 28 or 90 days. Tissue compatibility and biocompatibility were also demonstrated. In the subsequent CARE I clinical trials, there were no MACE at 30 days for 19 patients. Six-month angiographic and IVUS results are expected in June 2007. In December 2006, the first patient was enrolled in Biotronik’s first-in-man study, ProLimus I, which is examining the company’s ProGenic DES. The ProGenic is based on the company’s PRO-Kinetic cobalt chromium stent. ProGenic also utilizes the PROBIO silicon carbide passive stent coating, a bioresorbable poly-l-lactic acid (PLA) polymer drug carrier and pimecrolimus. The ProLimus I trial is a prospective, nonrandomized, multicenter study examining the safety and efficacy of the ProGenic. In April 2007, the first patients were enrolled in Relisys Medical Devices’ COREL clinical trial. This prospective, open-label randomized trial will enroll a total 150 patients to examine the efficacy of the company’s Corel+C DES. The coating on this cobalt chromium stent elutes paclitaxel, which is incorporated into a macroporous nano-structured carbon-composite matrix developed by CINVENTION. Encouraging animal trials were completed in April 2007 in Washington, DC.
Biodegradable DES Take the Stage
In the DES industry, the term “bioabsorbable” has been used interchangeably. In some cases, it has referred to the coatings on the stent and, in other cases, to the stents and coatings in their entirety, which degrade until nothing remains. These biodegradable stents prop open the vessel, deliver an anti-restenotic drug and then, with its job completed, dissolve and leave behind a healthy vessel. However, one of the primary debates in regard to biodegradables is whether they will remain viable long enough to effect the necessary therapeutic benefit. Within the biodegradable DES camp, there are polymers and metallics. Polymers have been utilized for their ability to dissolve promptly. However, studies conducted over the last few years show that in some cases, bits of polymers may be left behind undissolved—and any rough surface in the vessel provides ready ground for restenosis. (This can be a particular problem for polymer matrices covering durable stents.) There is also the question of whether polymers can provide optimum biological incompatibility. In experimental models, polymers have proven to incite a greater inflammatory reaction than inert materials. In addition, the biological response to a polymer is dependent on its formulation (including chemical structure and bulk load) and the time required for dissolution. Fortunately, polymer is not the only biodegradable material available to device developers. Some researchers have shown promising results related to development of degradable metal stents constructed of magnesium (Bernhard Heublein, et al., Hannover Medical School, Hannover, Germany) or iron (Matthais Peuster, et al., Georg-August University, Germany). To date, most research on metallic stents has involved magnesium (Biotronik is the leading developer in this area with its magnesium-based AMS stent), however, magnesium’s durability and stiffness reportedly can be less than optimal, hence the interest in iron-based stents. In most cases, research and development of biodegradable materials is still at an early stage. Only a handful of companies are known to have a fully bioresorbable, biodegradable stent in development (see chart, “Fully Biodegradable Cardiovascular Stents”). None of these biodegradable stents have yet received FDA approval, but progress is being made. Abbott Vascular’s everolimus-eluting BVS stent began first-in-man clinical trials in March 2006. Six-month results from the ABSORB trial (presented at the March 2007 ACC and CRT meetings by Principal Investigator Dr. Serruys) showed the BVS barely outperformed a bare metal stent in a panel of 26 patients. But more importantly, there were no reports of MACE or cases of acute or subacture stent thrombosis at 30 days. Dr. Serruys did note that higher-than-desired late loss rates led to a redesigned, next-generation stent that will be used in the next round of studies, starting soon in Europe and New Zealand. Bioabsorbable Therapeutics, Inc. (BTI), is working with a stent dubbed IDEAL, in which salicylic acid is incorporated into a polymer backbone. In addition, sirolimus is initially eluted from the stent and total degradation occurs within six months of implant. The balloon-expandable stent has produced positive results in porcine studies comparing it to a bare metal stent and Cordis’ Cypher. BTI is also looking at additional applications for the device, such as treating nonobstructive vulnerable plaque, gene transfer for infarct repair, and angiogenesis. At CRT 2007, trial results were reported for REVA Medical’s resorbable stent. Positive preclinical studies have paved the way for the first human clinical trial (RESORB) to begin in 2Q07 with a bare bioresorbable stent. A bioresorbable paclitaxel-coated version will be tested as well, beginning in 4Q07. REVA’s bioresorbable stent is deployed into the artery with a unique slide-and-lock design. In summary, the sheer proliferation of information related to established or new DES over the past year point to a market that, while in flux, is here to stay. In spite of unexpected complications, the performance of many DES still surpasses other therapies available—provided a proper patient population is identified. Within the next few years, the market can expect to see several new stents launched, giving clinicians more options than ever for patients who can benefit from stent placement.
There’s nothing like a $5 billion-plus market to generate a lot of debate.Â With that much money hanging in the balance, there was already enough incentive to fire up opposing advocates on the sides of (1) bare versus drug-eluting stents, (2) CYPHER versus TAXUS, (3) bypass versus angioplasty/stenting, and countless other polemics without the results of a new study to make yet another comparison.Â The Courage study, published in the March 26, 2007 edition of the New England Journal of Medicine, compared the benefits of stents with the use of an aggressive regimen of medicines in patients with stable coronary artery disease. The bottom line?Â
“PCI did not reduce the riskof death, myocardial infarction, or other major cardiovascularevents when added to optimal medical therapy. ”
Given that that kind of statement is an “in your face” to the stent industry, one cannot be surprised at the reactions.Â According to WSJ, Donald Baim, CEO of Boston Scientific, dismissed the results as nothing new, saying it was an “unlikely thesis” that stents would have reduced the number of cardiovascular events (or death) in the long term and that the real benefit of stents has always been to improve the quality of life.Â That’s a bit disingenuous, isn’t it?Â It is a real stretch to believe that stent manufacturers have truly limited their promotion to the “quality of life” idea.
The study was controversial enough with the stakes this high.Â Â Â The study is also not quite definitive considering several facts.
The study did not compare drug-eluting stents against optimal medical therapy, since the study preceded the release of the newer stents.Â Â Of course, this is not as big an issue as it might have been before the late-stage thrombosis problem of drug-eluting stents emerged and began causing interventional cardiologists to shift back to bare stentsÂ or, gosh, optimal medical therapy.
There are countless drugs in development by companies who will willingly argue that “optimal” medical therapy has not yet even been developed, but will be soon.
There may never be a “definitive” answer to the question of the “best” therapeutic option for stable coronary artery disease, since it remains a moving target in the crosshairs of multiple alternative technologies.Â In 2008, Abbott may well gain approval for its Xience stent, and other manufacturers’ drug-eluting stents are to follow.Â Â Needless to say,Â a new study would certainly be indicated at that time.
One reason why the Courage study has stirred things up so much is that the stable coronary artery disease segment of the stent market represents such a large share of the stent market (bigger arguably than the share represented by the use of stents following heart attacks or as an alternative in any case to more serious intervention, such as CABG) and is precisely the segment that “optimal medical therapy alone” targets.
ThereÂ has not yet been any evidence to suggest that the $5 billion worldwide juggernaut, otherwiseÂ known as the market for drug-eluting stents, had any risk of imploding overÂ the increased risk of clots following implantation.Â Â However,Â as we predicted, the occurence of late-stage thrombosis associated with drug-eluting stents is having a de facto impact on this market, even if leaders J&J and Boston ScientificÂ have not ascribed much to either the risk or the prevalence of the problem.
As today’s Wall Street Journal articleÂ notes, theÂ very real impact includes depressed sales for both Boston Scientific and J&J, an ostensible increase in attention by new stent manufacturers on the clot problem and an inevitable increase by the the FDA in the length of post-approval studies (up to five years).Â
In the October 2006 issue of MedMarkets, we provide a more comprehensive listing of the drug-eluting stents under development (subscribers only), including stents under development by Abbott Vascular, Avantec Vascular, Beijing Lepu Medical Device, Biosensors International, Biotronik, Blue Medical Devices, Boston Scientific, Conor Medsystems, Cordis (J&J), CorNova, Devax, DISA Vascular, Endovasc-TissueGen, Estracure, JW Medical Systems, Medtronic, MicroPort Medical, MIV Therapeutics, OrbusNeich , Relisys Medical Devices, REVA Medical, Sahajanand Medical Technologies, Sorin Biomedica Cardio, Terumo, Translumina, Vascular Concepts, X-Cell Medical andÂ Xtent.
Orthopaedic devices are a major contributor to the global medical device market, accounting for almost $26 billion in 2006, and with a growth rate that reflects growth in the medical sector overall. The table below gives a market growth projection for the five years 2007-2011.
The current valuation of the orthopaedic biomaterials segment is around $5 billion, representing over 17% of the orthopaedic total. It is also estimated that this market segment will grow at 10-12% a year, that is more than double the rate for the overall orthopaedics market. At this rate the biomaterials segment will achieve a value of $9.5 billion by 2011 and will represent 28% of all orthopaedic product sales.
The global market for orthopedic biomaterials is analyzed in a new report from MedMarket Diligence (mediligence.com).
Shift in use of refractive types, growth by country…
Refractive surgery is performed using a number of surgical techniques, each designed to minimize the patientâ€™s dependence on eyeglasses and contact lenses. Although there are many options to improve refractive error making it a complex field for the surgeon, while at the same time offering a broad range of options to treat each patientâ€™s unique needs, some approaches will grow at a greater rate while other refractive surgery options will be cannibalized by these faster growing techniques or they will be relegated to serving the needs of niche populations. For those techniques that serve a particular niche population, manufacturers will struggle with how to maintain visibility for these sub-population therapies while ensuring that clinical competence will be maintained at a level to allow the surgeon to deliver the outcomes that are feasible.Numerous factors come into play as the market for refractive surgery evolves:
Clinical Outcomes â€“ documented clinical advantage will not only encourage physicians to embrace new approaches to refractive surgery, it will help clinicians to determine the subset of patients that are most likely to benefit by one technique over another.
Physician Education â€“ the speed with which surgeons can be trained on the new techniques
Access â€“ how rapidly will the market adopt the technology that is necessary to perform the procedure and how quickly will the market be penetrated
Patient Education â€“ the ability of physicians and marketing efforts by manufacturers to inform patients of various options
Cost â€“ Significant differences in price to the patient as well as cost associated with training and equipment by physicians and ambulatory care centers
Reimbursement â€“ insurers willingness to pay for such procedures will continue to be a factor in a patientâ€™s decision to undergo refractive surgery
The net effect is that custom LASIK will soon constitute a dominant share of refractive procedures.
Globally, the U.S. dominates the market for refractive surgery products, but strong growth is evident in many countries.
The worldwide market for orthopedic biomaterials — allografts, synthetic bone substitutes, bone growth factors, polymers, ceramics, etc. — is growing steadily due to a concurrent evolution of surgical procedures, the emergence of innovative products and a dynamic and growing patient population. Select segment growth in this worldwide market is shown at right.
Data drawn from forthcoming MedMarket Diligence report, “Emerging Trends, Technologies and Opportunities in the Markets for Orthopedic Biomaterials, Worldwide.” (publishing Nov/Dec 2006)