Aortica: Taking Aim at Complex EVAR with a Novel Endograft Fenestration Technology

Transcription

1 36 START-UPS IN DEPTH: EVAR Aortica: Taking Aim at Complex EVAR with a Novel Endograft Fenestration Technology MARCH 30, 2016 Vol. 3, No. 5 by MARY THOMPSON Bellevue, WA Contact: Tom Douthitt, president & CEO Tomdouthitt@aorticacorp.com Year Founded: 2014 Who s Behind It: Benjamin Starnes, MD, Chief of Vascular Surgery at the University of Washington s Harborview Medical Center in Seattle; and Chad Robins, president of Adaptive Biotechnologies Corp. and Aortica s Board Chairman AORTICA CORP Unmet Clinical Need: A simple, cost-effective way to create highly accurate, patient-specific fenestrated endografts for complex abdominal aortic aneurysms Solution: The AortaFit System: using the patient s CT scan, the company employs a sophisticated computer algorithm to create a highly accurate and cost-effective personalized 3D printed template of the patient s diseased aorta that enables physicians (or graft manufacturers) to easily and precisely add fenestrations to an existing endograft Funding to Date: $7 million in a Series A round, primarily from Angel investors Board of Directors: Chad Robins; Benjamin Starnes, MD Scientific Advisory Board: Frank J. Veith, MD, Professor of Surgery at New York University and the von Liebig Chair in Vascular Surgery at the Cleveland Clinic; Juan C. Parodi, MD, Chief of Vascular Surgery, Trinidad Hospital, San Isidro, Buenos Aires; Stephan Haulon, MD, Chief of Vascular Surgery, Lille University Hospital, France; Zachary Arthurs, MD, Chief of Vascular Surgery, Brooke Army Medical Center, San Antonio TX Growth in the $1.5 billion global endovascular abdominal aortic aneurysm repair (EVAR) market has slowed to the low-to-mid single digits in recent years, as competitive pressures weighed on standard endograft pricing and manufacturers labored to develop new technologies capable of expanding EVAR to more complex cases. In fact, these forces helped drive significant consolidation in this space last year. In 2015, mid-tier EVAR pure-play Endologix Inc. merged with TriVascular Technologies Inc. in a deal valued at about $211 million (TriVascular, which offers a low-profile, proximal sealing endograft, went public in April 2014); UK-based Lombard Medical Inc., which has an endograft for patients with highly angulated aortic necks, bought EVAR start-up Altura Medical Inc. (developer of an ultralow-profile endograft) for $23.5 million upfront, plus milestones; and industry leader Medtronic plc completed two EVAR deals: a $110 million acquisition of Aptus EndoSystems and its graftsecuring EndoAnchor technology, and an undisclosed investment in Arsenal Medical s Arsenal AAA LLC subsidiary that included an exclusive option to acquire the company. Arsenal AAA is developing a polymer foam-based sacfilling technology also used to stabilize endografts. (See Top Stories of 2015: The Year in Review, The MedTech Strategist, January 19, 2016.) All of these deals are designed to make the acquiring companies more competitive by bringing in promising new technologies most of which are aimed at improving the durability/stability of EVAR procedures and/or addressing the roughly 60% of abdominal aortic aneurysm (AAA) patients with more complex disease anatomy. The latter includes those with shortneck aneurysms (5-10 mm graft landing zones, which make it difficult to stabilize the endograft) and aneurysms that are close to or encompass important blood vessels that branch off the aorta, such as the renal arteries, which supply blood to the kidneys, and the superior mesenteric artery (SMA), a

2 START-UPS IN DEPTH: EVAR 37 major blood vessel supplying the digestive system. According to Endologix, only about 25% of these complex AAA cases can be treated with existing endograft technologies. As a result, most of these patients currently must go the much riskier route of open surgical repair, or physicians may attempt to treat them off-label using standard EVAR endografts, with varying (and sometimes unfortunate) results. Complex cases brought in only about $300 million in annual endograft revenues in 2015; however, the total opportunity, if the right technologies were available, is more like $1.5 billion per year hence the flurry of activity in this space (see Figure 1). Start-up Aortica Corp. hopes to help address this unmet need by providing a user-friendly, fast, and uniform process for creating branch vessel fenestrations in existing endografts. Based in Bellevue, WA, Aortica is developing the AortaFit System, comprised of the company s proprietary Fenestration Alignment Software; a patient-specific, 3D printed template; and a fenestration kit that enables users to easily and precisely modify existing endografts, adding fenestrations, or holes, in the exact location of the renal arteries and SMA. The technology can be applied one of two ways. The first is by way of a Physician Modified Endograft (PMEG), whereby physicians can modify a standard endograft just prior to the implantation procedure. The second is by incorporating the AortaFit technology into the direct manufacture of an endograft. The technology is designed to provide the first quick, easy, and costeffective way to construct fenestrated endografts, thus making it safer and more practical to extend EVAR to complex cases. have been many previous attempts to address the issue of juxtarenal aneurysms, the solutions developed thus far have run into technical or logistical/cost issues that have kept them from achieving widespread market adoption, and in some cases, have kept them from making it to the market at all. It is clear from past experience that this is no easy task. However, Aortica has several things going for it that could increase its chances for success. For one thing, the company was co-founded by a physician Benjamin Starnes, MD who is considered one of the experts in the country on physician-modified fenestrated endografts. Starnes, who is currently chief of vascular surgery at the University of Washington s Harborview Medical Center in Seattle, learned the technique several years ago under the tutelage of Roy Greenberg, MD, of the Cleveland Clinic, who essentially pioneered physician-modified grafts and fenestrated EVAR (aka FEVAR) in the Figure 1 Worldwide EVAR Market Snapshot Complex AAA Market, Breakdown by Type Suprarenal (no neck) 39% Juxtarenal (< 5 mm neck) 19% Short Neck (5-10 mm) 42% US (Greenberg was the first US physician to conduct a physician-sponsored IDE-approved trial of the technique). Starnes, a widely acknowledged expert in treatment algorithms for patients with ruptured aneurysms, began using physician-modified fenestrated endografts to treat patients at Harborview and started his own IDE study in January At the time, he was measuring and creating his fenestrations manually, which Douthitt notes was very time consuming, very labor intensive, and costly. With the help of researchers at UW, he began working on a way to simplify the process. That work resulted in the development of a sophisticated software algorithm and 3D printing process capable of creating a personalized template from the patient s CT scan, showing physicians exactly where to place the fenestrations to achieve the best outcome for each patient. In mid-2014, Starnes, along with Chad Robins, president of Adaptive EVAR Revenues 2015 $0.9B $1.2B 2020E $1.0B $0.5B $1.5B According to Tom Douthitt, Aortica s president and CEO, complex EVAR is a market in need of new technology. He points out that although there Source: Endologix Traditional AAA, Treated Complex AAA, Untreated (Opportunity) Complex AAA, Treated Traditional AAA, Untreated (Opportunity) Online print subscriptions, reprints, and web posting and distribution licenses are available. Contact Kristy Kennedy at k.kennedy@medtechinno.com MARCH 30, 2016

3 38 START-UPS IN DEPTH: EVAR Biotechnologies Corp. in Seattle, cofounded Aortica to commercialize the system. The company was incorporated in September 2014, with Douthitt on board as CEO, and it closed on a $7 million Series A financing in November of that year. Douthitt has an extensive background in the cardiovascular device arena, going back to the 1980s when he worked as part of Eli Lilly s business development group (prior to Lilly s device business divestiture). He helped launch the first four cardiac stents developed by Guidant, long before its eventual acquisition by Boston Scientific, and eventually made his way into the start-up world, where he was involved with several companies targeting the vascular and structural heart spaces. Prior to joining Aortica, he served as general manager of sales and marketing for CircuLite Inc., a company with a unique, miniaturized partial ventricular assist system for earlier-stage heart failure patients that was acquired by Heartware International Inc. in When he was approached by Starnes and Robins to take the helm at Aortica, Douthitt realized the company had the potential to influence AAA treatment in a very big way. Figure 2 AortaFit 3D Printed Template Source: Aortica Corp. Just about anybody can do a CT scan and make a 3D printed image of the aorta and then try to use that to properly place fenestrations, he notes. But Aortica s predictive Fenestration Alignment Software algorithm uses a multi-factorial process that not only determines the precise location and size of the branch arteries, but also takes into account the degree of angulation in the patient s natural aortic anatomy (90-95% of patients have some degree of aortic angulation, he says) as well as the impact of the procedure and the graft itself on the final anatomy. All of this information helps dictate the exact location where the fenestrations need to be placed in order to ensure optimal graft positioning and stability. Essentially, Douthitt says, the algorithm can take a CT scan of a highly angulated aorta and straighten it out so that a simple template can be constructed. Equally important, the company aims to make the entire process easy for physicians. All the physician needs to do, says Douthitt, is provide a CT scan of the patient and the company does all the calculations and the up-front planning. We take the CT scan and do the analysis, and we come up with a blueprint of where the fenestrations need to be located on any endograft. For a PMEG procedure, that blueprint consists of a 3D printed, sterilized plastic tube that provides a straight-line replica of the patient s anatomy and shows exactly where the fenestrations should be placed (see Figure 2). All of the anatomical angulation is accounted for in that tube, notes Douthitt, as is the impact [on the post-implant anatomy] of each device and tool used in the procedure. So all the physician has to do is slide that tube over the partially deployed graft and mark where to make the fenestrations. The entire process to create, sterilize, and ship a patient-specific template takes only a few days, so the company will be able to get the template back to the physician in less than a week, he says. Aortica also plans to provide a tool kit that will enable physicians to easily make a consistent fenestration in any endograft of their choosing. Douthitt is reluctant to provide details on that component right now, but says the kit will offer a unique, fast, and very uniform way of making fenestrations. Longer term, the company intends to offer both the software and the kit to endograft manufacturers to facilitate the direct manufacture of a fenestrated endograft, thereby avoiding the physician modification step. Cook Medical Inc. is currently Aortica s closest competitor, with its custom-made ZFEN (Zenith Fenestrated) endograft. However, Douthitt hesitates to call Cook a direct competitor, noting that he believes the two companies technologies are complementary. The ZFEN is an excellent technology, but actually using the ZFEN remains extremely complicated, time-consuming, and costly. It takes hours for physicians to fill out all the paperwork and do all the measurements and calculations for the ZFEN, says Douthitt, and they must have access to expensive equipment in order to even make the required mea-

4 START-UPS IN DEPTH: EVAR 39 surements. Moreover, once they place an order for the device, it takes six to eight weeks to get it back, and the total cost of each ZFEN is extremely high. In comparison, Douthitt says Aortica s process could be used with any endograft (including a ZFEN), dramatically simplifying upfront planning and making the process more affordable as well. It will add to the cost of a standard endograft, he says, but the total cost will not be in the same neighborhood as current FEVAR devices. The cost and complexity associated with current FEVAR devices, notes Douthitt, have proven to be substantial barriers to physician adoption of this technique. In fact, he says, that is why many physicians, particularly in Europe, have turned to cheaper, off-the-shelf alternatives for juxtarenal disease, such as the use of chimney grafts. That technique involves placing covered stents alongside the exterior of the main graft body and extending those from the proximal fabric edge down into the renal arteries to maintain blood flow to the kidneys. Although the use of chimney grafts (or CHIMPS) is generating a lot of enthusiasm right now among physicians, Douthitt points out they may not be the ideal solution for juxtarenal disease. There are several challenges with CHIMPS, he explains. First of all, the procedure itself is not particularly easy. Second, the process of placing a tubular stent next to a tubular graft can create a gap, or gutter, between them, increasing the risk of dangerous Type I endoleaks. Finally, the chimney stent must have both the radial strength to preserve its lumen when compressed by the endograft, and the flexibility to make a right angle turn into the renal artery. But, notes Douthitt, there is currently no single stent that adequately satisfies this dual requirement. Studies show, he continues, that the best clinical outcomes are achieved when less than two chimneys (on average) are placed per patient. Given that most people have two kidneys, this becomes problematic when trying to achieve relatively complication-free treatment of the aneurysm while maintaining blood flow to and preservation of the kidneys. Consequently, the applicability of this technique will likely remain limited. The cost and complexity associated with current FEVAR devices have proven to be substantial barriers to physician adoption of this technique. Physicians may also choose to treat juxtarenal AAA disease with a standard endograft, attempting to anchor the graft in less than 15 mm of aortic neck. However, notes Douthitt, it is very difficult to get a secure seal and an effective anchor in a space the size of a coffee bean. Patients treated off-label with these short neck solutions often experience higher rates of endoleak and mortality. Our aim is to anchor the graft very high up in the aorta. If you can get 40 mm of neck length, you end up with a really tight seal and secure anchoring, because you re now up in healthy, parallel aortic tissue. He points out that FEVAR studies performed by Dr. Starnes and others suggest that if you can get that extra neck length and still preserve the renal arteries, then you really have something [Starnes has seen no Type 1 endoleaks in more than four years of follow-up with FEVAR]. And, if on top of that we can simplify the procedure, then it s win-win-win. Our fundamental belief, Douthitt continues, is that of all the tools out there [to address juxtarenal and shortneck aneurysms] including chimneys, branch technology, and fenestrated EVAR fenestrated EVAR is the best option. The challenge is that in its current form, it s complicated, time consuming, and costly. As a result, he says, very few physicians either want to attempt it or are successful when they do try to attempt it. I think the ZFEN experience teaches us that even when you have a very nice graft, the complexity of the procedure in its current form can slow adoption regardless of how many physicians are trained. Aortica hopes to change that dynamic in a big way. And Douthitt foresees several ways for the firm to generate revenue from the AortaFit technology. The company plans to supply templates directly to physicians on a caseby-case basis for graft modification on the procedure table during its initial clinical evaluations, but the long-term objective is to work with endograft manufacturers to add the template/ fenestration process to the end of the manufacturing line, he says. The latter could be accomplished by partnering with one specific manufacturer, or the company could remain device agnostic and license the technology to any interested manufacturer, with Aortica collecting a per-graft charge. It is not our intention to develop our own endograft, so we need to work in collaboration with the graft manufacturers either as a supplier or a partner. Douthitt says the firm is approaching this market with the assumption that it will remain independent; however, that could change. We like the approach of licensing our technology, but there are also market dynamics that make a partnership ap- Online print subscriptions, reprints, and web posting and distribution licenses are available. Contact Kristy Kennedy at k.kennedy@medtechinno.com MARCH 30, 2016

5 40 START-UPS IN DEPTH: EVAR pealing, so at this stage we want to keep all our options open. The company is engaged in ongoing dialog with nearly every endograft manufacturer at the moment. They re all very interested in what we re doing, says Douthitt, but we are still early in the clinical process, so we are taking it one step at a time. To date, Dr. Starnes has implanted about 80 fenestrated endografts as part of his IDE study, but only a handful thus far have used the Aortica process. The company just received FDA approval in January to add its software to Starnes study, and four cases were done with the Aortica template in February, using several different manufacturers endografts. Aortica has plans to expand the study protocol to other sites before the end of 2016 and then determine exactly how it will structure a pivotal trial and whether that will be conducted independently or with a partner. If all goes well, the pivotal study could begin in the latter half of That milestone is likely to require some additional funding. The company, which, as mentioned, raised $7 million in its Series A round, primarily from Angel investors, may initiate a Series B venture round later this year. Aortica s technology addresses a very large market opportunity, notes Douthitt, who says nearly 80% of AAA patients currently treated with open surgery plus about half of those being treated off-label with standard EVAR endografts could be eligible for FEVAR. In the US, which is the largest EVAR market (the US and EU account for more than 80% of all EVAR procedures), there are some 75,000 AAA patients each year who need repair, and about 75% are currently treated with EVAR. Applying Aortica s model to the US market adds up to a potential US FEVAR patient population of more than 31,000 per year (see Figure 3). What we re trying to do is get to a point where the provision of fenestrated EVAR is simple for a physician, says Douthitt. If you can simplify the FEVAR process, and personalize vascular therapy for the individual patient, then I think you open up fenestrated EVAR a less-invasive, highly desirable therapy to more physicians who are anxious to offer their patients improved treatment options, and to a group of patients who were previously either treated suboptimally with a standard EVAR device or had to go to surgery. I think we have the potential, with this technology, to significantly improve patient care and in so doing, reignite growth in the AAA market. Figure 3 FEVAR Potential US Market, US AAA Annual Incidence 175,000 Severe AAA Disease (requiring repair) 74,500 Mild-Mod AAA (Conservative Tx) 100,500 EVAR 56,000 Open Surgery 18,500 Standard EVAR appropriate 23,500 Challenging Anatomy 32,500 Anatomy limited 14,800 Other Causes 3,700 >50% are candidates for FEVAR All are candidates for FEVAR FEVAR Candidates: (Surgically treated or Suboptimal EVAR) >31,000 (~40% of AAA Repairs) Source: Aortica Corp.