Contrarian Play in Cardiology:

Transcription

1 6 UNDER THE LENS JUNE 30, 2015 Vol. 2, No. 12 Elixir Medical s Contrarian Play in Cardiology: by STEPHEN LEVIN Go Bioresorbable or Go Home Built on the efforts of innovative start-ups, interventional cardiology has matured to become the province of large strategics. Elixir Medical is looking to challenge that hierarchy by helping lead the conversion from metal stents to bioresorbable scaffolds, and in the process build what the industry hasn t seen in a while: a significant new cardiology company. Innovation in interventional cardiology has changed significantly over the past few years, reflecting the changes taking place throughout the industry. The impact on cardiology is noteworthy because the specialty has, over the course of its nearly 40-year history, served as the model that device innovation has followed in the industry as a whole. Interventional cardiology was built on technology; specifically, the conversion from surgical to percutaneous procedures, which were made possible by a new generation of devices, starting with balloon angioplasty in 1977 and continuing through the stent revolution. These devices generally came from venture-backed start-ups that developed innovative technology, with the most successful pioneering start-ups emerging as mid-to-large cap players themselves, e.g., Guidant, or being acquired and serving as the basis for large companies cardiology businesses, e.g., AVE/Medtronic Inc., Scimed/Boston Scientific Corp., and Cordis/Johnson & Johnson. THE MEDTECH STRATEGIST 2015 Innovation In Medtech, LLC. All rights reserved.

2 UNDER THE LENS 7 Things started to change with the advent of drug-eluting stents (DES), which required greater resources on all fronts, particularly R&D, clinical trials and regulatory, to develop and commercialize these drug/device convergence products, putting them beyond the reach of most start-ups. At the same time, along with these product-specific challenges, cardiology innovation was slowed by systemic issues, most notably unpredictable regulatory and reimbursement hurdles, particularly the rising bar of clinical evidence required, which increased the cost and complexity of studies and lengthened the time to market. Combined with the flight of venture capital from medtech, which has hit early-stage financing particularly hard, and changes in the economics of healthcare delivery most notably the increased influence of economic buyers, broadly defined, and the declining influence of physicians in product purchasing as more doctors become hospital employees, reducing their role in product adoption interventional cardiology is no longer the hub of innovation it was in its halcyon days. Percutaneous coronary intervention (PCI) procedure growth declined before ultimately plateauing, in part because cardiology has become a victim of its own success with current technology resulting in fewer re-do procedures and therapies like statin drugs keeping many patients out of the cath lab in the first place. While there are still unmet clinical needs that present opportunities for investors and entrepreneurs, the rules of the game have clearly changed, making cardiology a riskier and less attractive sector. (See The Future of Cardiovascular Innovation: An Insiders View, The MedTech Strategist, March 30, 2015, and Innovation in Cardiology: The Glass Remains Half Full - An Interview with William Wijns, The MedTech Strategist, April 27, 2015.) The result has been fewer dollars invested and fewer start-ups emerging in this area. And even though there was little product overlap other than drug-eluting balloons in the Medtronic/Covidien deal, the large company landscape is shrinking (particularly with J&J s decision to exit cardiology by selling Cordis to Cardinal Health), and, as importantly, has not seen a new player join its ranks in a generation. (See J&J s Cordis Divestiture Hints at Changes to Come in Medtech, The MedTech Strategist, March 30, 2015.) Apparently Motasim Sirhan, CEO of Sunnyvale, CA-based Elixir Medical Corp. didn t get the memo outlining how the interventional cardiology market has changed. Founded in 2005, Elixir has set its sights high. The company is looking to help pioneer the fourth major wave of technological change in cardiology (balloon angioplasty to bare-metal stents to DES) to bioresorbable scaffolds (BRS), but Elixir does not intend to stop there. The company has also developed a line of drug-eluting stents, which instead of using an existing drug, employ a proprietary agent developed in-house. And while it is starting with vascular applications, both coronary and peripheral, Elixir also is working on applying its existing platform technologies to other clinical areas. Sirhan s vision for the company extends well beyond the traditional single device M&A exit route. He is building Elixir for the longterm, with a platform of innovative products. Going Back To Their Roots Sirhan s grand plan for Elixir is not surprising given his roots. An engineer by training, Sirhan has worked in the device industry since 1990, when he joined Advanced Cardiovascular Systems (ACS, which pioneered over-the-wire balloon angioplasty catheters). He remained with the company through its acquisition by Eli Lilly & Co. and eventual spin-out as Guidant. Sirhan s experience with a start-up that grew to become a major cardiology company sparked his entrepreneurial interest. In 2000, he left Guidant and formed Avantec, an interventional cardiology products company that was acquired in 2002 by Japan s Goodman Co. for $165 million ($135 million plus a previous investment of $30 million). Having built a company that was focused on a successful but narrow group of cardiology products, Sirhan had broader goals when he launched Elixir in He notes, Elixir was founded with the goal of becoming a leader in interventional vascular drug/device therapy. His timing could not have been better. Not only was Sirhan fresh off his successful sale of Avantec, but this was also the heyday of DES, which were on their way to approaching what some at the time estimated could be a $6 billion market worldwide. It was also a period in which investor interest in medtech was peaking. Sirhan looked to capitalize on this momentum by building an organization that had internal expertise capable of developing both drugs and devices, thereby creating a company with skillsets well beyond those of traditional medtech start-ups. Several experienced device executives joined him at Elixir, including former Guidant colleagues. One of the things that we felt strongly about was to create an organization equally comfortable in developing drugs and devices, Sirhan explains. That would allow us the compelling advantage, when looking at a clinical challenge, of developing a drug formulation, a drug/device combination therapy, or a device alone, depending on what was called for, all within one company. Elixir has tried to remain largely below the radar for most of its first ten years, preferring to focus on R&D. In that time, the company successfully developed and patented its own anti-proliferative drug, and developed three stent products, along with an advanced catheter platform. Online print subscriptions, reprints, and web posting and distribution licenses are available. Contact Kristy Kennedy at k.kennedy@medtechinno.com JUNE 30, 2015

3 8 UNDER THE LENS Drug Development: A Unique Challenge Elixir was not alone in its efforts to try to combine device and drug development under one corporate roof. The growth of the DES market sparked a burst of interest in drug/device convergence products, which were going to be the next hot product segment, addressing a variety of clinical needs. The problem was that these companies found out how difficult the drug development process was, while also learning about the challenge and cost of simultaneously maintaining the different skillsets and corporate cultures required for drugs and devices. Veteran device executive Paul LaViolette described the process of developing a DES while he was COO at Boston Scientific this way: Think about the most difficult product development project and this is harder. Unlike most companies that ventured into the convergence product arena without success, Elixir emerged with a proprietary drug, Novolimus. Nonetheless, Motasim Sirhan believed that Elixir needed to develop both drug and device capabilities for the company to compete with market leaders in cardiology. In his view, There is a plateau of what devices alone, whether they are mechanically or electrically oriented, are able to reach in order to achieve the necessary clinical efficacy. It became evident that we needed a drug/device platform to take therapies to the next level. Sirhan admits that LaViolette was right, but Elixir found that out the hard way. When we embarked on developing our drug, we knew it was a difficult challenge, he says. The reality was that it turned out to be a lot more difficult than we ever imagined. However, unlike most companies that ventured into the convergence product arena without success, Elixir emerged with a proprietary drug, Novolimus, a metabolite of Sirolimus, the drug used by Cordis/J&J for its ground-breaking Cypher DES. Elixir sought an agent that would not be categorized as a new molecular entity (NME) because that would require a longer, more complex regulatory pathway. The company s researchers discovered that as Sirolimus goes through the liver, the result is the metabolite that Elixir called Novolimus. When synthesized into a drug, the company found this metabolite to be stable, active, and of the same potency and effectiveness as Sirolimus and with the same safety profile, which enabled it to avoid the NME route. Elixir patented Novolimus both for oral applications, as well as for use on devices, and uses an outside manufacturer to produce the drug for its products. Of Stents and Scaffolds Parallel with its drug-development program, Elixir was also working on two scaffold R&D programs: one based on metal and the other on polymers. (The terminology can be confusing; on one hand, stent and scaffold can be used synonymously, with the latter often employed to define the former. Within the industry, usage has evolved, and most now employ the word stent when describing a permanent implant and scaffold to describe bioresorbable devices, which is how the terms will be used here.) According to Motasim Sirhan, A stent is not a scaffold. A scaffold does not necessarily go into a vessel to shape it; a scaffold supports the vessel and then goes away, so it is a gentler approach to intervention, as opposed to a stent, which essentially uses brute force to re-shape the vessel and stays behind permanently. While Elixir s lead product is now its DESolve BRS, which employs a polymeric scaffold, that was not etched in stone when the company was founded. From the outset, Sirhan made sure the company was exploring all possible options. In his view, If you are going to enter a space with a plan to lead it, you need to have a road map. Some of your products are short term, some of them medium term, some of them long term. For all of them, your execution plan has to include risk mitigation, not just one idea because what happens if things go wrong? And things will always go wrong. Elixir s multi-pronged development program has generated three different product platforms encompassing baremetal stents (BMS), DES and bioresorbable devices. Aware that helping convert the market to bioresorbable scaffolds would be a longer term project, Elixir knew it had to develop a world class drug-eluting stent in order to establish itself as a player alongside the cardiology market leaders. This is another element of the company s strategy that runs contrary to conventional wisdom. Once a hotbed of start-up activity, new DES companies are now few and far between for the reasons outlined above. Yet, Sirhan believed that having a workhorse drug-eluting stent was essential for Elixir to establish itself as a legitimate presence in cardiology. The result is the company s DESyne cobalt chromium stent line, which includes versions with a durable and a bioresorbable polymer (the DESyne and the DESyne BD). Elixir executives claim that the DESyne stent features the lowest drug dose among DES on the market and the lowest polymer load for improved biocompatibility. The DESyne BD incorporates Elixir s bioresorbable expertise through the use of a polylactide polymer that dissolves within six-to-nine months. According to Sirhan, this design also obvi- THE MEDTECH STRATEGIST 2015 Innovation In Medtech, LLC. All rights reserved.

4 UNDER THE LENS 9 ates the need for a primer layer coating, which allows for a true bare-metal surface after the polymer biodegrades. Part of Elixir s strategy to remain stealthy for as long as possible was to give the company the time necessary to establish the clinical data required for it to demonstrate that its devices were as safe and clinically effective as those currently on the market products that for the most part have a much longer clinical pedigree. Elixir s clinical trial data, which is now five years out, showed that DESyne produced late lumen loss (LLL, a surrogate endpoint for restenosis commonly used in DES trials) at nine months similar to Medtronic s Resolute and Abbott Vascular s market leading Xience V, and 82% less than Medtronic s Endeavor. Similarly, the DESyne BD produced comparable LLL at six months as Resolute and Xience V, and the same 82% reduction versus Endeavor. The company s DES also demonstrated superior safety profiles, including an 8% rate of MACE (major adverse cardiac events) over five years, lower than most other devices, and a 61% reduction in cardiac events. Both of Elixir s drug-eluting stents are CE mark approved, with DESyne on the market in Europe, Asia and the Middle East, and DESyne BD now ramping up for commercialization. Bioresorbable Has Always Been the Future While Elixir has developed and is commercializing a competitive DES platform, Motasim Sirhan acknowledges that, from its inception, Our vision was transforming the industry to employ resorbable scaffolds. That kind of transformative strategy takes time and requires heavy lifting for a start-up company. Fortunately for Elixir, the company doesn t have to carry out this missionary selling effort on its own. Sirhan acknowledges that Elixir is fortunate to be following in the wake of Abbott s Absorb BVS (bioresorbable vascular scaffold, which received CE mark approval in 2011) since it s much easier for a large company to break new ground and attempt to change physician practice patterns in a large market like cardiology. At present, bioresorbable devices are only used in around 5% of PCI procedures globally, in part due to the additional cost of the devices, and none are yet available in the US. Abbott hopes for approval later next year. As noted, when Elixir was launched, the company immediately undertook two parallel R&D efforts in BRS, a metallic and a polymeric approach, with the understanding that it would take time to determine which one Elixir would ultimately pursue. Realizing the risk was enormous on a startup company to develop this new technology, it was important that we have short- and intermediate-term products that would allow us to establish the sales and operations infrastructure to get into the market and pave the way for the scaffold when the R&D efforts produced real products, Sirhan explains. Now we have achieved those milestones and are ready for our primary mission, which is converting the market from stents to scaffolds. At present, bioresorbable devices are only used in around 5% of PCI procedures globally, in part due to the additional cost of the devices, and none are yet available in the US. Abbott hopes for approval later next year. He estimates that it took Elixir seven-and-a-half years to develop its BRS, and suggests that would not have been possible had the company not also developed its other products, primarily the drug-eluting stents. In Sirhan s view, The market needs justify us having a next-generation drug-eluting stent, but having the DESyne products also enabled us to generate revenue and build infrastructure, like operations, all under the same roof, which allowed us to accelerate our R&D activities for the bioresorbable products. If we did only the scaffold, we would have developed a technology, not a company. While standard CEO-speak is to say you are building your company to be a stand-alone entity, in reality, few companies are actually prepared for that eventuality; most are best suited to be M&A targets. As a start-up, Elixir is a rarity: it s not only building multiple product lines, but the infrastructure necessary to sustain an independent company. That s something that strategics don t generally value in start-ups since functions like operations and sales and marketing are likely to be subsumed by the larger player upon acquisition, but which Elixir considers essential for its strategy of driving, as a small company, adoption of bioresorbables, a major new product category. The Ultimate Goal: A Golden Tube The premise behind bioresorbable vascular devices goes back to the genesis of interventional cardiology with socalled plain old balloon angioplasty (POBA). For many patients, POBA was quite successful at opening blockages and, by virtue of not leaving any implants in the vessel, this procedure allowed the normal healing process to proceed unimpeded, without any device to obstruct the blood s natural flow dynamics, which is the ultimate goal of bioresorbables. The result often was significant positive lumen remodeling with the vessel allowed to return to its normal shape and an increase in the size of the channel through which blood flows. The problems, however, were that, with nothing in the vessel to keep it open, many patients suffered from Online print subscriptions, reprints, and web posting and distribution licenses are available. Contact Kristy Kennedy at k.kennedy@medtechinno.com JUNE 30, 2015

5 10 UNDER THE LENS abrupt closure of the artery due to a recurring thrombus or elastic recoil, or a gradual re-buildup of plaque (restenosis) that re-occluded the vessel. This cascade of outcomes occurred frequently enough to make it obvious that POBA alone was not the answer for many patients. The result was the metal stent revolution. Metallic stents successfully inhibited recoil and abrupt closure and reduced restenosis rates. However, along with those benefits, clinicians found that implanting a permanent metal stent also inhibited positive lumen remodeling by preventing the natural healing process or vasodilation through which blood flow dynamics would normally adjust the channel size and artery shape based on the patient s oxygen and cardiovascular requirements. With stents, suddenly you are caging the vessel, Motasim Sirhan explains. This produces a good initial result that deteriorates over time. That deterioration is generally the result of neointimal hyperplasia, the process by which smooth muscle cells proliferate within the vessel walls, exacerbated by the continuous presence of stents, resulting in thicker arterial walls and narrowing the lumen, a process that can lead to restenosis, neo-atherosclerosis or late stent thrombosis (LST), the last of which continue to be a problem even with the latest generation DES. The exact causes of the increased risk of these late adverse events following stenting are not completely understood; indications are that multiple factors may contribute to the problem, including lesion complexity, sub-optimal stent deployment, chronic inflammation elicited by the polymer, a possible toxic side effect of the drug, recurring atherosclerosis, and cessation of dual anti-platelet therapy (DAPT). The uncertainty notwithstanding, a common factor contributing Figure 1 DESolve Serial OCT Imaging Up to 3 Years Source: Elixir Medical In-vivo Confirmation of Golden Tube to several of those potential causes is the permanent implant in the vessel. In Sirhan s view, the best way to eliminate the various possible causes of late events is with bioresorbable scaffolds. These devices are the best of both worlds. They combine the positive elements of POBA positive lumen remodeling and leaving nothing behind while eliminating recoil and abrupt closure due to recoil, allowing the vessel to return to its pristine, natural state with no permanent implant, what we call the golden tube, he says. The result of this therapy would thus be to match the acute performance of DES while also providing long-term restoration of natural vascular function; one without the other would not be enough to provide value and command a premium price given the realities of the current cardiology market. (see Figure 1). To achieve those goals, Elixir ultimately decided to pursue its polymeric, rather than metallic, BRS platform. Most of the bioresorbable scaffolds currently being developed are polymer-based, including Abbott s Absorb, Fortitude from Amaranth Medical Inc., and ART from Terumo Medical Corp./ Arterial Remodeling Technologies (all PLLA), REVA Medical Inc. s Fantom (tyrosine-derived polycarbonate polymer), and Bioabsorbable Therapeutics Inc. s IDEAL (salicylate-based polymer), while Biotronik Inc. s DREAMS scaffold is made of a metallic (magnesium alloy). However, some clinicians contend the jury is still out on whether polymer or metal makes a better scaffold. The metal advocates point to the success of metallic BMS and DES, and claim that polymers can trigger inflammation, require thicker struts to achieve sufficient scaffolding strength, and are harder to expand, less deliverable, break more easily, and have a shorter shelf life. Polymer supporters point to the hydroxyapatite ring formed around the vessel after degradation of the metallic scaffold, noting that leaving such material behind has longterm implications for patients. Elixir had to essentially fight a product development battle on two fronts. Not only did the company need to produce a device capable of demonstrating non-inferiority, at a minimum, to DES in the short term for acute performance, as well as long-term advantages, but it also had to demonstrate that DESolve successfully addressed some of the early problems encountered by other BRS. These potential challenges include both utilization and patient outcome issues. For example, the early THE MEDTECH STRATEGIST 2015 Innovation In Medtech, LLC. All rights reserved.

6 UNDER THE LENS 11 bioresorbable scaffolds suggested that the clinical benefits of the device were delayed based on looking at lumen enlargement at three years. In addition, the deliverability and range of use (determined by types of patients; for example, the devices are not effective for calcified and bifurcated lesions) were limited compared with DES, and there were problems with device fractures when the scaffolds were over-expanded. Faced with those challenges and the relative success of existing drug-eluting stents, Motasim Sirhan admits, You can understand why BRS have only achieved a very small share of the market [to date]. No matter the price, the chances of getting substantial market share are slim unless we address physicians clinical efficacy and safety concerns. New Jargon: Degradation and Resorption To address the acute performance and ease of use issues, Elixir designed DESolve to provide good radial strength and support, including low recoil, along with over-expansion capability to reduce the risk of fractures. The scaffold s profile and deliverability are similar to current drug-eluting stents, while also featuring a self-correcting capability in case of malapposition (when the scaffold separates from the vessel wall, DESolve re-adjusts its position), which has been a problem with earlier BRS. The result has been clinical outcomes comparable or superior to DES, as demonstrated by MACE, late lumen loss and acute stent thrombosis rates. DESolve is also designed to effectively restore long-term vascular function by degrading within one year and eventually leaving no implant behind (except for two small platinum markers that remain for fluoroscopic landmarking) through a process called resorption, while also continuing to maintain conformability as the vessel reshapes. Data from the company s CE mark trial, the DESolve Nx study, a 126-patient trial conducted at 13 sites in Europe, New Zealand and Brazil, demonstrated 9% lumen growth at six months, something never before seen, and a MACE rate of 5.69%, comparable to the leading DES. The struts of the first DESolve scaffold, which is CE mark approved, are 150 microns thick, the same as Abbott s Absorb. Later this year, Elixir will launch the DESolve 100, named for the thickness of this scaffold s struts. That compares with current DES such as Medtronic s Endeavor Resolute (91 microns), Abbott s Xience and Boston Scientific s Promus (both 81 microns). Along with introducing a new kind of device comes the burden of explaining new terminology. Beyond just the difference between stents and scaffolds, in discussing bioabsorbables, confusion emerged regarding the difference between degradation and resorption. Motasim Sirhan explains that degradation occurs first, referring to the process by which the chains of the polymer break down, resulting in the scaffold s molecular weight being reduced to a negligible amount. This takes approximately one year for DESolve, compared with three years for Abbott s Absorb, he says. Resorption is the process by which the mass of the scaffold diminishes, which takes 18 months for DESolve and five years for Absorb, according to Sirhan, and ideally leaves a pristine vessel, the so-called golden tube, by 18 months. The key, according to chief development officer Vinayak Bhat, is achieving the right balance of degradation and resorption because if the scaffold degrades too soon, it will not provide sufficient support, and if it takes too long to resorb, you risk the same MACE and thrombosis problems as with drug-eluting stents. Stefan Verheye, MD, PhD, a senior interventional cardiologist at the Antwerp (Belgium) Cardiovascular Institute, a consultant to Elixir, and a PI for the Elixir DESolve NX trial, admits that he never believed, based on pre-clinical data alone, how quickly DESolve would be resorbed. But now I have the three-year data confirming the scaffold is gone there s nothing there, which shows that the bench data was accurate, he says, adding, It looks like a juvenile vessel after three years, the classic golden tube. I ve worked with other bioresorbable scaffolds and I ve never seen anything like this. The next step for Elixir is to build the body of clinical evidence necessary to help persuade interventional cardiologists, a specialty that relies heavily on evidence-based medicine, of the benefits of BRS over DES. The company has finished enrolling its post-market clinical follow-up for DESolve and is currently enrolling the DESolve 100 clinical trial, with a post-market study to follow. The company recently initiated a 2,000 patient registry, and future plans include studies of other coronary applications for DESolve, including acute myocardial infarctions (AMIs), chronic total occlusions (CTOs), and bifurcated lesions. The study investigating use of another version of the device to treat AMI and CTO patients, known as the DESolve+, will begin later this year. This device will have the same mechanical properties as DESolve 100, with the additional advantage of the scaffold s ability to self-correct to 0.25mm above its nominal diameter, which could prove effective in diminishing the vessel wall malapposition that often occurs in AMI patients after the thrombus is removed and the spasm resolved, where the stent turns out to be under-deployed. Sirhan adds that AMI and CTO indications currently constitute 25-30% of the worldwide PCI market. A Platform with Diverse Possibilities Beyond coronary applications, Elixir s next area of interest for this technology is peripheral vascular disease. The company will begin a trial this year for lesions in the superficial femoral artery (SFA) and is also developing a scaffold for Online print subscriptions, reprints, and web posting and distribution licenses are available. Contact Kristy Kennedy at k.kennedy@medtechinno.com JUNE 30, 2015

7 12 UNDER THE LENS lesions below-the-knee. This technology will be pursued by a sister company spun out of Elixir, Akesys Medical. Elixir is also looking at a range of other potential other applications for the company s technology that will be developed by additional companies spun out of Elixir (see Figure 2). The next two are Cerona Medical, which is focused on vascular applications, specifically in neurology, venous and carotid, and Aigle Medical, which is exploring non-vascular technologies, looking first at possible opportunities in ear, nose and throat (ENT) and pulmonology. As we go forward, we want to establish core teams focusing on these technologies to develop the potential for commercialization, partnerships and collaborations, Sirhan says. Other areas the company is looking at include ophthalmology, hemorrhagic stroke, erectile dysfunction, and drug delivery in oncology. The funding for the entire family of Elixir companies, since its inception, has come primarily from The Invus Group, an evergreen private equity firm with more than $5 billion under management, based in New York City, and from Sirhan. Invus also funded Avantec and then agreed to partner with Sirhan to underwrite Elixir. Sirhan declines to disclose how much the company has raised to date, other than to say that Elixir s most recent financing raised $50 million in 2013 and the company still has more than half of that on hand, which he expects will carry it through to profitability. Sirhan characterizes Invus as a very patient partner who, as long as we are making progress and showing results, will continue to be supportive for the long-term, with no timelines for an exit. Time to Execute Having spent most of its first decade flying below the radar as it developed its product portfolio and the clinical evidence supporting it, Elixir is now transitioning to what Motasim Sirhan acknowledges is becoming more of an execution play. The company started its commercial efforts with the DESyne products, as noted, and then last year rolled out DESolve in Europe, the Middle East and Asia, with discussions underway with Japan s PMDA to start a clinical trial and begin the regulatory process there. Elixir also has started discussions with the FDA about a US clinical trial and about the process for introducing its pediatric stent. The company is selling direct in Germany and using distributors elsewhere. In addition to its California headquarters, Elixir has offices in Ireland, Belgium, India, and New Zealand, with a total of 75 employees. As the company enters this commercial phase, Motasim Sirhan holds steadfast to the vision of bioresorbable technology transforming interventional cardiology. If you talk Figure 2 Elixir Pipeline Targets a Segmentation Strategy Note: Pursuing through licenses to Aigle, Cerona, Indra, and Freya Medical Source: Elixir Medical THE MEDTECH STRATEGIST 2015 Innovation In Medtech, LLC. All rights reserved.

8 UNDER THE LENS 13 to cardiologists, the vast majority believe a conversion from DES to BRS is coming, that it makes sense, and it is the right way to go for patients, he says. Sirhan admits that cardiologists are divided on how this conversion will take place: one group sees this as an inevitable evolution that will occur, based on these devices demonstrating the kind of vascular restoration they are showing to date, and another is waiting for longer-term data. But all of them believe that, ultimately, the conversion from DES to BRS is a no-brainer and the current [market] under-penetration is because the first products are not yet ready from an acute performance standpoint, not because of skepticism about bioresorbability, he says. However, not all clinicians and industry executives are quite so confident about the future of bioresorbables. Their skepticism is not based so much on doubts about the capabilities of bioresorbable scaffolds or their potential advantages over drug-eluting stents; rather, their uncertainty results more from the changing health economic landscape. After all, they suggest, the current generation of DES have been quite successful in addressing coronary artery disease, and since BRS, like all stents and scaffolds, are primarily designed to improve quality of life, not save lives, will the system pay a premium for this new technology? Or phrased differently, will the traditional innovation model, which has rewarded angioplasty, baremetal and drug-eluting stent technologies with increased reimbursement rates, do the same for bioresorbables? One medical director of a major cardiovascular company that currently does not have a bioresorbable scaffold, himself an interventional cardiologist, is among the group of doubters. In his view, I ve not been a total believer in it because I think it s going to take an awful lot of evidence to insure that the quality of data supports the health economic value. I don t see paying a premium price for those technologies unless they have a benefit over ordinary technology, and that s terribly difficult to prove. As a result, he doesn t see the value of his company getting into BRS as a business, although he acknowledges that it has been actively exploring bioresorbable technology for a long time. He compares BRS to cars: We ve already got very fast cars that perform extremely well. Why do you need yet another one? Well, we don t need one, but sometimes we like to drive something else. We all like to drive very, very smart, fast cars. Are bioresorbable scaffolds like the latest luxury automobiles a nice to have, but not a need to have? In this executive s view, some of the stents we have now are already significantly outperforming the need, causing him to question whether we need that technology, let alone more advanced devices like bioresorbables. At the end of the day, he notes, We ve never convinced ourselves that we can make a stent that is as good as a metal stent out of a polymer. If you talk to cardiologists, the vast majority believe a conversion from DES to BRS is coming, that it makes sense, and it is the right way to go for patients. Motasim Sirhan Motasim Sirhan clearly holds a different view, believing that the traditional medtech innovation model, while evolving, still applies to truly innovative technology that demonstrates improved patient and economic outcomes and will reward those products with reimbursement premiums. In any market, as innovation plateaus and product cycles mature, you start seeing evidence of price erosion. That was happening in drug-eluting stents. It takes innovation that raises the efficacy bar in order to get growth and premium pricing. We are working on leading that next wave, he says. Indeed, Sirhan believes that bioresorbables can help push interventional cardiology over one of its most difficult hurdles: clearly demonstrating PCI s noninferiority to coronary artery bypass graft (CABG) surgery among many patients and also further expanding the market by showing how PCI can be superior to medical therapy in major patient populations. The ability to provide long-term vascular restoration has the potential to open the market to the 20 million stable angina patients who are not candidates currently for PCI, he suggests. We look at this as opening opportunities that are the future of interventional cardiology. To those who question the inevitability of bioresorbables, Sirhan is the man with a hammer and these prospective opportunities are all nails. In Sirhan s view, it is not a question of if, but when BRS will gain traction and see increased adoption. The transformation of the interventional space with resorbable scaffold technology is underway. How far and how quickly we can raise the bar to make it more of a standard therapy in terms of ease of use and range of use will be determined ultimately by how successful our pipeline is, he argues. This is a technology that has arrived. History is in the making and we are on the right side of history. Online print subscriptions, reprints, and web posting and distribution licenses are available. Contact Kristy Kennedy at k.kennedy@medtechinno.com JUNE 30, 2015