Industry Round Table: Where Are the New Devices?

Brian Firth (Cordis Corporation): As you all probably know, Cordis, in its entirety, is a cardiovascular device company, and now a combination drug/device company. There are four major divisions: 1) Cordis Cardiology, 2) Cordis Endovascular, 3) Biosense-Webster, which focuses on rhythm detection and management, and 4) Cordis Neurovascular, which focuses on intracranial issues. Cordis has just added a stroke group which operates across Johnson & Johnson and coordinates all of the company’s stroke activities. Sam Liang, who was vice president of marketing at Cordis Cardiology for many years, has moved to the new stroke division. Centocor, on our company’s pharmaceutical side, along with the various device companies, is engaged in this as well. We are trying to determine what the touch points are and what we can do to pull all of these things together in a more cohesive fashion. In the interest of time, I will touch only briefly on the two divisions of most interest to the audience here: Cordis Cardiology and Cordis Endovascular. Obviously, the major focus is and has been on drug-eluting stents at Cordis Cardiology. The Cardiology division is currently engaged in trying to answer many questions. There are 42 ongoing or completed clinical trials that attempt to address the various indications and areas where information has been lacking. Some of these are randomized trials and some are registries that cover such topics as in-stent restenosis versus brachytherapy. David Holmes is P.I. of a large U.S. study of in-stent restenosis. We are also studying left main, multivessel disease, bifurcations, diabetic patients, and so forth. Cordis is doing an enormous amount of work to address where these devices work and where they do not. It is very encouraging to see the long-term results from these studies. I was recently in Sao Paulo with Eduardo Sousa, where we looked at the four-year follow-up angiograms; they were absolutely beautiful. When the images at four months, twelve months, two years and four years are superimposed, the four-year images look just like the two-year images. This has been extremely encouraging because GAMMA 1 with brachytherapy showed that at three and four years, the event-free survival curves have completely come together — it’s not just that they’re not statistically significantly different, but they are superimposable at three to four years. Thus there has been late catch-up in GAMMA 1, and the same has occurred in GAMMA 2, which was our higher-dose study with brachytherapy. Similar data regarding several of the beta systems were presented in Europe. In light of that observation — and obviously we are talking about in-stent restenosis as opposed to de novo stenosis — it’s still an interesting observation, and we are not seeing these results at four years in first-in-main. The three-year RAVEL data will be presented at the next ACC meeting. As you know, the two-year RAVEL and SIRIUS data show these lines separating at one year, and then they run parallel. There are little “bumps”, as there is progression of native disease in both groups but the lines run parallel. In terms of next-generation products, Cordis is working on device changes on the delivery systems which are relatively easy to make and can be somewhat iterative. The next project involves changes in our stent platform. One of Cordis’s next-generation platforms, called “Select”, is a more flexible version of the Bx Velocity stent, but with much longer lever arms. These stents have already been released in Europe and elsewhere in the world and have been very well received. Next is a cobalt-chromium stent, which includes two generations — the first is called “Steeplechaser”. Cordis is continuously researching new drugs, but it is pretty tough to top what has been observed with sirolimus at this point. Cordis is evaluating different doses and different combinations. Unfortunately, what Philip Reid had to say on the drug side of things has some parallels on the device side. You think that you are putting stents into coronary arteries, but the FDA thinks you are placing a local drug delivery system in the arteries. In all but name, drug-eluting stents are being regulated as drugs. Thus, if a company makes a change to its delivery system or to the stent itself that may impact drug content, the FDA wants clinical studies to be conducted. The reality, therefore, is that all companies face a situation whereby what might normally have passed as a minor modification to a device in the bare-metal stent world, is now viewed by the FDA in a totally different light. Be aware, also, that Philip was discussing new products being launched every twelve to eighteen months. That cycle time will slow down due to regulatory changes. The FDA’s new regulations require pharmacokinetic studies, extensive concept development to achieve compliance, clinical studies, and so on. In the former device world, manufacturers were able to make what were called “in-line” changes, or staged “tweaks” that ultimately resulted in a new product, though the company would claim that it was the same as the previous model. With drug regulations, however, the story is very different. “Tweaking” is not allowed. For example, the FDA wants to see SDS changes; slight stent modifications require nine-month follow-up data, and significant manufacturing process changes require nine-month follow-up clinical data; new stent materials, significant design changes — all of these will result in delaying the introduction of next-generation devices. Drug-eluting stents are therefore being treated by the FDA as local drug delivery systems, and the device side of the business is faced with the task of jumping over some new regulatory hurdles. The FDA has placed these hurdles despite, for example, the REDOX study, which looked at the dose of sirolimus on Cypher stents at 40% and 70% of the currently available dose, and showed that there was no difference in outcomes. If you conduct a study with a different design, that is, only a 10–15% lower drug content, because it has lower surface area, the FDA wants to see clinical trial data. Philip Reid discussed the cost of entry to the marketplace for a new chemical entity, and gave the $1.5 billion figure — a number that continues to rise. It used to be $600–700 million. The cost of entry to the marketplace for a new drug delivery stent — considering all phases, manufacturing changes, etc. — amounts to hundreds of millions of dollars, probably around $600 million. Thus, it’s a very expensive business to enter. There are high barriers to entry, which means that very few companies can afford to get into the market. The second issue involves the return on investment. Jorge Belardi was asking me at this meeting about the penetration in Europe — and I told him that there was no such place! Europe is a figment of the American imagination. In Portugal, the market penetration is 60–70%, while in the United Kingdom and France, where reimbursement is offered, and in Germany, which is the largest European market and does not offer reimbursement, the penetration is only 5%. The entire business model has suddenly changed, and this is the leading edge for new technologies. We must not only ask the question: Where are the patients? But also: Where can we get paid for this product if we produce it? These questions require extensive study. In fact, David Holmes and I have written a paper to be published in JACC on the changing treatment paradigms with new technology. The new paradigm appears to be that though new technologies are desired, healthcare systems are only variably willing to pay for them. The days of “make it and they will buy it” are long gone. Manufacturers today must consider this new paradigm in terms of return on investment. That also impacts, for example, decisions regarding where products should be marketed. Companies in both the drug and device arenas worldwide are looking at this issue very carefully and are deciding not to enter even some major markets such as France and Germany if it will completely interfere with the business model they have developed. These are real considerations in terms of a finite amount of money invested that is expected to provide a decent return and, if you do it this way versus that way — is it a worthwhile proposition, or do you not enter that market at all? In addition to drug-eluting stents, Cordis is working on other areas such as vulnerable plaque, myogenesis and carotid arteries. Cordis Endovascular is working on carotid stenting. This will, however, be a much slower-growing market because FDA approval and CMS coverage, when it comes, will be limited to high-risk carotid stenting, which is 20-30% of the total. The FDA will require major trials before it agrees to an indication for lower-risk carotid stenting patients. Likewise, CMS will be evaluating this closely. This, I think, represents a huge step forward, at least based on the current data, but the program will be much slower-growing than some of the others because of the inherent issues that I’ve touched on here. Lastly, Cordis is extensively involved in abdominal aortic aneurysm work. Cordis is working with what was originally known as the Mike Marin device — the Fortran device — and we have been very pleased with our progress. Jamey Jacobs (Guidant Corporation): First, I want to thank the IAGS for inviting us here, as it offers those of us in industry a terrific opportunity to participate in an exceptional exchange that is refreshingly different from other meetings. Guidant feels that it is very important to focus on a few things and do them well. What guides the company toward that goal is to make every effort to leverage the fundamental aspects of our current technologies and capabilities, including the devices you are all familiar with, as well as some exceptional capabilities that we have built around polymer chemistry, controlled release, and a number of different pharmacological approaches. We will talk more about biologics later. Guidant is leveraging the platforms that can be tailored to our different customers. We are very interested in helping overcome your challenges. From a distribution capability standpoint, Guidant is viewed as one of the best in the market. Naturally, the financials associated with the business are necessary to keep us moving forward and allow us to invest a double-digit percentage of total sales back into R&D. Guidant seeks not just to be cost reduction-oriented, but also to bring customers new technologies that can reduce patient complications and the cost of medicine. Guidant had developed a plethora of new technologies, leveraged by way of the existing platforms. We have strong capabilities across a wide variety of materials. The bioabsorbable platform, for example, is viewed by our company as a material capability. We would like to hear from you regarding the most applicable areas and the most appropriate solutions. Matthew Pollman will talk about site-specific therapies, as well as a bioabsorbable stent that could provide different options in the future and carry different kinds of compounds. Just to let you know, Guidant is not only looking at Everolimus — a compound in which we have great confidence — but we are also looking at other drugs in concert with Everolimus, drugs that serve different aspects of the restenotic process and other diseases as well. Thus, Guidant is striving to make things safer from an antiplatelet/antithrombus standpoint, and is working to develop exceptionally strong anti-inflammatories, matrix deposition, and so forth. As Brian Firth mentioned, it is enormously challenging to get these compounds through the regulatory process, and this challenge increases by an order of magnitude as soon as these compounds are combined. Guidant is very actively pursuing these areas, not only with our partner Novartis, but with other companies as well. The list of areas that Guidant is interested in includes: 1) Diabetes, with dosing regimens or addressing the injury response or other mechanisms; 2) Bifurcation lesions: with the launch of a device soon in Europe; for regulatory and timeline reasons, our company wants to address bifurcation lesions with a drug-eluting stent approach in the United States, which will require a longer timeline; 3) Vulnerable plaque: Matthew will discuss this topic. Using Barry Rutherford’s idea of changing the spark plug if it’s fouled from the oil; we also want to address the “oil leak” using some other approaches and a more comprehensive view of vulnerable plaque. Also, we are aggressively pursuing the development of various devices and tools for access, as well as treatments for long-term results. Addressing the cardiovascular tool set for interventional cardiology is not where Guidant stops. We are also working on developing electrical stimulation and vascular imaging, minimally invasive valve repair and carotid artery treatment, as well as the many communication systems in terms of patient management. We believe that there is a significant need to integrate all potential data measurements that can be obtained from the devices and integrate them into the patient management system and the entire patient record system. We have a very aggressive program in place on the electrophysiology side of the company, and Guidant also sees it as a potential compliment for our interventional cardiology products. I would now like to pass the microphone over to Matthew Pollman. Matthew Pollman (Guidant Corp.): I am Director of the New Ventures Group at Guidant. My job is to look a lot further out into the future. We think that cell and biologic approaches, site-specific therapies and vulnerable plaque will become something that can actually be treated. Thus, I am given the task of deciding what types of programs need to be launched now in order to reach these goals, with the timelines that are associated with the standard pharmaceutical industry, which is 7 to 10 years out. Briefly, vulnerable plaque, biologics and all of these therapies can be bundled under the very large umbrella of site-specific therapies which can extend beyond just the cardiovascular system. As we leverage some of the technology platforms that we already have developed —bioabsorbable stents, for example — these devices could be applied in areas beyond the cardiovascular system. We are all familiar with the concept of vulnerable plaque. We had an extremely interesting discussion the first day of this conference on this topic. We all realize that there are challenges in understanding exactly how to diagnose vulnerable plaque and its natural history and course, as well as the best therapy to employ. Even though we also believe that there will be headway made in the future from a pharmacologic and system standpoint — and recognize that vulnerable plaque is a systemic disease — we will still face the challenge of a patient on the table in whom you have fixed the culprit lesion with a drug-eluting stent, but there is another lesion and potentially another artery that is supplying a very large territory that looks ulcerated — perhaps with a 40–50% stenosis. Do you leave that alone, wait for another day, or go in and intervene now that restenosis is potentially not a problem? These are some of the issues that Guidant is trying to address. In terms of trying to diagnose vulnerable plaque and determine what exactly a vulnerable plaque is, we have been very active, particularly at Massachusetts General Hospital, in using OCT as a diagnostic tool to better understand the characteristics of this lesion. And, more importantly, Guidant is very interested in conducting a vulnerable plaque natural history trial so that we can understand its progression. An evolving theme as we move forward is how to develop much more targeted solutions, not just within the cardiovascular system, but beyond as well. The realm of site-specific therapy provides Guidant’s position statement about what exactly a site-specific therapy is. Due to PK-PD issues, there are therapeutic agents such as small molecules, proteins, DNA-RNA strategies, viral vectors and the evolution of the use of cells, whereby either due to systemic toxicity problems, or a limited local therapeutic site concentration, target organ effects are limited. These are challenges that we faced at Millennium Pharmaceuticals. Thus we know that a site-specific therapy whereby a high concentration and a sustained release, if needed, are locally delivered, would actually alleviate many of these issues that are involved with standard drug development. And certainly, the vascular highway is a good way to deliver such agents. If you think about this progression, this continuum and this concept are not strange to you — it goes beyond just thinking about intervention in myocardial infarction and heart failure. Rather, there’s a pathophysiologic process continuum where there are points at which you could intervene if the right tools were available. This (slide) lists some compelling therapeutic targets in terms of the pathophysiology involved in this continuum that starts at the time of vessel occlusion, leading down this cascade that could ultimately lead to heart failure. I want to highlight just a couple of them because they were touched upon in the preceding session. Apoptosis, for instance, has a lot of compelling scientific data suggesting that cell death plays a large role in this cascade and the continuing cycle, particularly that of local deterioration, local myocardial death, and progression on to a more regional problem. As for inflammation, we need to find a local delivery strategy and learn how to target it at the right time in the right patient; these are very intriguing targets and should not be ignored. However, they are plagued with many of the same problems faced by the pharmaceutical industry in terms of systemic side effects. They are still good targets, but we must develop a way to adjust the delivery methods so that systemic side effects are no longer a factor. These are some of the issues that Guidant is presently working on. The future regarding the building blocks of biologics seems to point to the fact that the therapeutic agent, ultimately, in all interventions is the cell — whether an autologous cell, an allogeneic cell source, or an endogenous cell. A local delivery system for the cell and the therapeutic agent is necessary, whether via catheter access or an infusion strategy. More important is the local site action. How do you attract and retain the cells that lead to this healing and repair process, whether they’re autologous or endogenous or allogeneic cells? These are the basic building blocks that facilitate the therapeutic agent’s action. And how can we better promote and direct localized strategies for the action of these cells in this healing and restoration process? Again, these are very active areas of interest for Guidant. Through the vascular highway, access to all of the organ systems is possible, and the CNS in particular provides another area where this type of therapy would be amenable, whether through biologics or a site-directed type of therapy. Not to say that these areas don’t present some problems, but we all understand that new solutions often lead to new problems. Brian articulated this very well earlier: the past century was very straightforward, dealing with one section of the FDA, primarily one payer, and very straightforward IP positions on new technology iterations. However, while the same players are still here, device companies are now experiencing new FDA pathways that are somewhat uncharted territory. The same could be said for the FDA; this is an evolving field and the FDA must determine how to deal with these new combination and site-specific therapies. It involves much more complex interactions such as partnerships with pharmaceutical and biotech companies, each of which really haven’t learned to work well together. As a community, we need to be aware of these problems. Guidant is confident that we can work through them to deliver the next generation of therapies. Matthew Jenusaitis (Boston Scientific): I have no slides to present here. I come from a different background; I’m more of a business guy and less of a scientist. I was thinking about Dr. Christian Bernard, who performed the first heart transplant in 1961 in South Africa. Shortly thereafter, he traveled through Europe giving presentations. He hired a chauffeur to drive him from place-to-place — from Vienna to Salzburg and then on to Germany, France, and so on — to give the same presentation. After about 15 presentations, Dr. Bernard was tired of doing the exact same thing, so he told the chauffeur, “these people have no idea what I look like. Let’s switch clothes. You know the presentation as well as I, so why don’t you give it?” The chauffeur reluctantly agreed to do it and began to speak before the audience. The chauffeur did it perfectly; every slide was just right, he covered each and every bullet point, and finished to tremendous applause. He then began taking questions from the audience. Since he had heard all of the typical questions before, he knew how to correctly answer them. Finally, someone in the audience raised his hand and asked about the socioeconomic implications of this procedure and how it would impact the field in the future — a question the chauffeur was unprepared for. He had no idea how to answer it. The chauffeur replied: “Doctor, that is the stupidest question I have ever heard!” Thus, I’ll have my chauffeur answer any such stupid questions you may have for me today! There are a couple of things I see taking place in the new device arena. First, the business is growing and is primarily controlled by four companies. Approximately 1 million interventions and 4–5 million diagnostic procedures are performed each year in the United States. The market is currently at approximately 3 billion dollars and is expected to evolve into a 6–7 billion dollar market with drug-eluting stents in the United States. This growing market is primarily controlled by four device companies that are getting bigger and bigger, and developing new products is becoming increasingly difficult. Second, large companies have a fundamentally different approach to new product development. Large companies are very focused on defending market share and mitigating risk. Small companies, on the other hand, are very focused on speed-to-market; they don’t have much to lose. Third, the large companies have mortgaged a lot of their new product development to support drug-eluting stents that are a primary force in the industry. Drug-eluting stents will create a 3 billion dollar growth opportunity for the industry. Thus all of the big companies are plowing a significant amount of money into drug-eluting stents and are trying to get into this part of the market. From my viewpoint, large companies, for all of these reasons, are turning increasingly to smaller companies as R&D partners to develop new products. We will see a lot more merger, acquisition and joint venture activity in the near future. Boston Scientific has been doing some work in the area of drug-eluting stents and other new products that are a combination of organic research — and many of these partnerships are with smaller companies. A large area of development for Boston Scientific involves abdominal aortic aneurysm and thoracic aortic aneurysm repair. Boston Scientific has partnered with a company called Trivascular. We have also partnered extensively with a couple of interventional cardiology companies: EPI, for distal embolization, and IVT, for cutting balloon technology. In the area of carotid stenting, Boston Scientific has its own Wallstent platform and is partnering with Endotex, which has a carotid stent platform as well. Boston Scientific plans to launch more vascular sealing products, and will partner with a company called Claris. Boston Scientific will continue to pursue partnerships with smaller companies to further our product development plans. In doing so, our company will be able to continue to drive the evolution of new product development in this risk-averse world. Kirk Garratt: Thank you, that was terrific. Let’s open the discussion up to questions. Richard Heuser: In relationship to what you just addressed about partnering with smaller companies, let’s look at two fields mentioned in Guidant’s presentation here: 1) vulnerable plaque, and 2) chronic total occlusions. Last fall’s meetings in the Asia-Pacific showed vulnerable plaque, both OCT and virtual histology. I don’t know what the heck that means, but it sure looks exciting. I look at that technology — two weeks ago we had the CTO Club meeting in New York where live cases were conducted. There was more excitement at that meeting than I’ve seen at any meeting since Andreas Gruentzig was alive. It has basically been brought about by fairly small companies that have really costly jobs to do. I wonder how many of these small companies are going to be able to use this technology; we won’t be able to talk to them until they have tested their products in humans — and not just in a few patients, but in phase two and phase three trials, which are very expensive. How are these small companies going to survive long enough to arrive at the partnership level with the larger companies? Don’t tell me that you want to do it all in-house, because in-house R&D doesn’t always reflect everything that’s out there in the marketplace. Jamey Jacobs (Guidant): You are absolutely right; it’s not going to be done solely in-house. There are numerous small companies we need to partner with. One way Guidant has chosen to do that is through equity investments by which we continue to nurture the small company mentality rather than try to absorb “Jonah within the whale” — because Jonah gets spit out most of the time, or he dies. The idea, therefore, involves more of a “nurturing” through a venture capital-type approach. If things work out, the larger partner has the first right of refusal. I don’t think we are going to wait until there is a broad human experience from phase two or three trials. As preclinical models develop, we will have earlier and earlier confidence, because as many of us have learned, when a product is absorbed from a small company at the late stages, there is very little opportunity to deal with the small company’s quality system and finalization of the product that will be submitted to the regulatory process. Too much has already been fixed at that point. Thus we do need to work with companies earlier on in the product development process. Thomas McNamara: I am not an interventional cardiologist, thus I have a different set of questions, one of which is: What is the feasibility and likelihood that we are anywhere near having magnetic resonance (MR)-compatible stents? I am essentially a diagnostic radiologist and I foresee MR imaging taking over my field. The stainless steel artifact is a problem in terms of MRI. Second, the markets you are talking about pale in comparison to venous disease, which is very disabling, and once it develops, there is very little in terms of treatment options currently available. It seems to me that we have the best chance of helping these patients by immediately treating their clot before they wind up with a scarred vein, which is a source of obstruction and valve reflux. The worst combination is obstruction and reflux. Currently, there is no truly satisfactory device for the removal of clot, nor a well agreed upon drug regimen. In cases where you can’t get to the clot soon enough, the obstructions can be stented and rendered patent, but this cannot be done with valves, particularly now with the availability of good anticoagulants. Another huge market involves all of the various lines that go into patients. Patients have lots of trouble with clotting off, the apparent solution to which is to pull the line out and put it in someplace else where it still runs the risk of clotting off. There is also the risk of infection when the line is pulled out. Those lines that aren’t pulled out early stay in for quite a long time, and invariably wind up being associated with a stenosis. Why is that? And how can it be prevented? Matthew Jenusaitis (Boston Scientific): As the industry goes through this change with drug-eluting stents, companies will start to plow this money back into the development of technologies in these other areas. As Jamey mentioned, this is all leverageable technology. Venous stenting is technology that can be leveraged from coronary artery stenting technology. The products, of course, are not the same. Peripheral stents for the arterial system will be different from stents for the venous system, and of course, coronary arteries. The issue involves harnessing the resources and focus of the company to move through this step change with drug-eluting stents so that some of the money can be plowed back into other R&D areas. We must do this in conjunction with partnerships with other companies that are actively working in a particular area and try to “bet” on some of these things, like Dr. Heuser said. Then we must buy these products wholesale as opposed to post-FDA approval retail. In this way, companies will be able to combine technologies to address needs in other areas. Alex Martin (Cordis): In terms of MR incompatibility, we have been working on this for all of our interventional products. I can tell you that the solution is quite a ways off yet — we’re currently in the very early stages of understanding the requirements for MR compatible products. Cordis is working initially on ensuring our therapeutic devices such as stents and guide catheters will be compatible. For stents, this will be challenging because of the design implications and regulatory hurdles that result when you change materials or dimensions of a drug-eluting stent. Kirk Garratt: What is it that’s incompatible? Is it just a materials issue or is it the fact that leads are a problem, as they act as an antenna? Something is needed to conduct electricity to the pacemaker or defibrillator. All of those things are likely to serve as an antenna. Is it a question of physics that we’re up against? Matthew Jenusaitis (Boston Scientific): I think it’s a question of the material as well as the geometry of whatever device you’re making. Unfortunately, due to the intellectual property constraints in many of these cell designs, there often isn’t much you can do about the geometry of the stent cells. Thus, the problem involves a marriage of these two aspects. Jamey Jacobs (Guidant): Some materials, such as cobalt chrome, are more MR-compatible and produce less artifact. At the same time, these materials must serve two masters: they must be well visualized under fluoroscopy, and they need to produce minimal artifact under MR. On top of that, these materials must offer all the mechanical properties, such as elongation, to resist cracking. There are very few materials that fit the bill. We are looking at some materials that have not yet been used in vascular applications. I agree that finding a material that fulfills all of these requirements is a ways off yet. Kirk Garratt: Tom, you had a question about biocompatibility of long-term dwelling catheter systems. Thomas McNamara: These various tubes placed in patients require coatings that will be resistant to both thrombosis and infection. The coating would not necessarily be continuous, but it could be potentially refreshed by modifying the device or material. What exactly causes the stenosis at very predictable locations in the line? Perhaps we could place a coated stent and then insert the device through the stent. It would be initially expensive, but this hasn’t really been looked at. The solution has until now been in the hands of our surgical colleagues whose approach is to pull the line out and put another one in. It’s a tradition and also makes sense as the proprietor of a new tube. I think we could design tubes that are able to prevent these things from happening in the first place. Perhaps there’s a coating that could be replenishable through another channel or outlets added to the side of the tube. Barry George: Many of us here have gone through the ACS thing, the Guidant thing, the Boston Scientific SCIMED thing — we’ve developed intimate relationships with many in the industry. Sometimes the uniforms and the ball caps change, but the main players are the same. There used to be a line of communication with a company whereby a physician in the field could discuss what was needed with his/her industry contacts. We knew who to talk to and where to go. If I have a particular problem with a drug-eluting stent or a guidewire, I now have no idea who to talk to. Sure, I could talk to the local representative in the field, but that’s not enough. Let’s face it — you guys are the “big four”, and it’s like the record companies back in the 1960s where there were one-hit wonders that either played for one of the record companies or they were gone forever. I think you need to get back to the basics and return to your roots — return to what made things move, the things you can do to facilitate turning the Queen Mary around in the port and address these issues. You’ve got the FDA and Medicare hovering over you, but you’re missing the boat on a lot of things. Take venous disease, for example, which I’ve become interested in the past year. I’ve been doing deep venous stenting for years. There is a huge population of patients with deep venous disease, and then there are the access issues as well. How do things stand with this? Not only that, even if we wanted to help you companies, we physicians don’t know who to talk to. It’s like you said, you’re worried more about protecting your market share than addressing some of these product issues. Jamey Jacobs (Guidant): I do think it’s important to return to making sure that there’s a close relationship with those outside of our adviser team. Oftentimes, companies listen to those they want to, and over time, the process becomes a bit inbred. I challenge all companies, Guidant included, to revitalize our strategy regarding who we work with and become more open to listening to the nay-sayers, not just the cheerleaders. It’s exchanges like these that we are open to and that challenge us in a positive way. Patricia Thorpe: Drug-eluting stents work so well in the coronary system, but it’s so frustrating to be an interventional radiologist who treats so many vascular access patients with stents, which are more effective than angioplasty alone, but then seeing restenosis in these stents, particularly in the ...?... and the subclavian artery. For years, I’ve been pleading for a coated stent for patients with subclavian problems, because stenting the subclavian artery promises a 50–75% guaranteed restenosis rate within 2 to 4 months. A huge patient population deserves the technology that will transfer to stents larger than the 5 to 6 mm coronary stents. Alex Martin (Cordis): We are working on the problem of restenosis in the peripheral vascular system but you can expect drug delivery devices to have a much longer development and regulatory cycle. First of all, our resources have been primarily focused on coronaries. Secondly, since the peripheral vascular bed is different from the coronaries, product development will take additional time to understand the drug dosing and release requirements. Matthew Jenusaitis (Boston Scientific): May companies have invested a lot of time and money in the biodegradable materials area; there are a lot of good biodegradable materials now. The issue for us has always been that transition time between when the material begins to biodegrade, when it fully degrades and what happens to the pieces. Where do those pieces go? Do they end up in the lungs? We will continue to work on this, but it will take time. In terms of subclavian disease and drug-eluting stents, all of the companies involved want to leverage drug-eluting stent technology and apply it to other parts of the body. But as was mentioned in the previous session, these trials are expensive. The FDA mandates that huge resources be applied to proving the product’s safety and efficacy before bringing it to market. So it’s not so much a question of missing the boat, rather, it’s a question of only having enough money to buy one ticket to ride the boat. There are four boats sailing at the same time, so a company must decide which one it will buy a ticket to sail on. We eventually want to get on all of the boats, but we are forced to be selective at this time. Richard Heuser: Along the lines of what Patricia and Tom mentioned, I’m not going to say that we need better patient education, because that would sound too altruistic. I’m in this to make money like you companies. In the U.S., there is a complete underutilization of treatment for patients with venous disease — it’s unbelievable. Our country also undertreats patients with claudication. Every person who needs Viagra also needs to be screened for vascular disease, because it’s a common problem that signals early-onset vascular disease. Marv Woodall, in the old days when J & J was developing stents and iliac stents were approved, talked about doing some very focused advertising for patients with claudication. As a physician, I’m all for that kind of advertising. I hope you companies will consider doing that, because it would truly be a public service and also would be good for business. On the venous end of things, it would be a public service because these patients are not getting treated. Perhaps the drug manufacturers (t-PA, etc.) should be doing these patient education ads for venous disease, and device companies could pick up the slack as well. Jamey Jacobs (Guidant): I agree with you wholeheartedly. In addition to just “general awareness”, our company has been making an effort to address women’s health issues, a subject that currently has a lot of traction. This focused education strategy has the potential to dramatically increase awareness in the population for a terribly underdiagnosed group of patients. Guidant has put money into this and hopefully other companies will take on other areas.