East Meets West I by Jonathan Goldstein

Wednesday, October 9, 201 3

Vol. 17, No. 195

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Aptus eyes favorable results from ANCHOR post-market study

EndoGastric Solutions seeking RESPECT for GERD treatment

Aptus Endosystems (Sunnyvale, California), a company pioneering solutions to enhance aneurysm repair, reported positive initial results from its ANCHOR postmarket registry evaluating the use of the Heli-FX EndoAnchor System in endovascular aneurysm repair (EVAR). These early results from the first 250 patients demonstrate the safety and acute technical success of utilizing Heli-FX in primary and revision EVAR procedures. There are two arms for the registry taking place in both U.S. and European sites. One treatment arm is for patients being treated in the primary setting with the prophylactic use of the anchors. This is a situation where the physician is concerned with the anatomy of the patient. The other arm is the revision and these patients have been See Aptus, Page 6

EndoGastric Solutions (EGS; San Mateo, California) reported Tuesday that enrollment for the RESPECT study (Randomized EsophyX vs. Sham/Placebo Trial) is complete and has surpassed the company’s original target of 120 patients. EGS designed the RESPECT study to generate additional level one evidence supporting the transoral incisionless fundoplication (TIF) as a treatment for gastroesophageal reflux disease (GERD). There were two treatment arms in the study. Patients were randomized, in a two-to-one ratio, to either the treatment group which received the TIF procedure followed by an ongoing course of placebo medication, or the control group which underwent a sham procedure followed by administration of proton pump inhibitor (PPI, omeprazole) medical therapy. See EndoGastric, Page 7

The Israel Connection

Washington roundup

By JONATHAN GOLDSTEIN Medical Device Daily Israel Editor

By MARK McCARTY Medical Device Daily Washington Editor

By OMAR FORD Medical Device Daily Staff Writer

East meets West in Israel’s bio-universe A Chinese proverb states: When the wind of change blows, some build walls, while others build windmills. In both China and Japan today, the winds of change are blowing towards windmills of collaboration, to maintain and/or improve their technological position. During the past few weeks, a westerly breeze seems to be supporting these winds: a number of independent, unrelated events between Israel and the Far East have taken places that indicate a trend towards increased profitable cooperation into the future. In a number of creative and potentially far-reaching moves, innovative relationships and business models are See Israel, Page 8

By AMANDA PEDERSEN Medical Device Daily Senior Staff Writer

Recent warnings hint MDR draft in force during comment period FDA warning letters have cited device makers routinely over medical device reports, and the agency has responded with a 54-page draft guidance dated July 9. Despite the sizeable draft, only four comments were posted to the regulations.gov website by the last day of the comment period, although a quick read of some recent warning letters suggests the agency had started emphasizing the points found in the draft before the comment period had expired. FDA’s device branch issued an Aug. 12 warning letter to Deroyal Cientifica (La Aurora de Heredia, Costa Rica) citing the question of when a manufacturer “becomes aware” of an adverse event involving a medical device (Medical Device See Washington, Page 9

Don’t miss today’s MDD Extra: Oncology

Inside:

CombiMatrix partners with TRPN for lab diagnostics . . . . . 2 Amaranth raises $20M Series B to support Fortitude . . . . . . 3

To subscribe, please call Medical Device Daily™ Customer Service at (800) 477-6307; outside the U.S. and Canada, call (770) 810-3144. Copyright © 2013 Thomson Reuters. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com.

Wednesday, October 9, 2013

Medical Device Daily™

Agreements/contracts

CombiMatrix partners with TRPN for lab diagnostics A Medical Device Daily Staff Report

CombiMatrix (Irvine, California), a molecular diagnostics company specializing in DNA-based testing services for developmental disorders and cancer diagnostics, has entered into a contractual agreement with the health insurer, Three Rivers Provider Network (TRPN), for coverage of its diagnostic laboratory services. TRPN is an international network with a global arm called World PPO that provides health care access to more than 100 million members, including 15 million in the U.S. These members now have access to CombiMatrix’s suite of molecular diagnostic solutions and comprehensive clinical support – specializing in prenatal, miscarriage and pediatric healthcare. “We are very happy to enhance our coverage for our members and the addition of CombiMatrix’s advanced diagnostic laboratory services is an important new offering for us in the area of prenatal and pediatric health,” said Christopher Quintana, Chief Operating Officer for TRPN. “We look forward to working closely with CombiMatrix.” CombiMatrix CEO Mark McDonough noted that the addition of the extensive TRPN network is another milestone for the company. The partnership will also add

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Coming Thursday in the MDD Interview ‘People need treatment every day. We can not stop.’ In this second part of the MDD Interview, Francesco Benatti recounts how logistics and fast work amid the rubble kept up the flow of dialysis products for patients after the Italian facility of B.Braun was crushed by two murderous earthquakes in May 2012. new marketing and distribution support, he added. Three Rivers Provider Network says it has evolved into the largest and fastest-growing proprietary PPO network in the U.S. The TRPN network is comprised of more than 600,000 total providers, including more than 5,000 hospitals and 70,000 ancillary facilities. Through its clients, more than 15 million people have access to the TRPN PPO network. Coupled together with World PPO, the global arm of TRPN, they provide access to some of the most internationally acclaimed healthcare providers representing more than 1.5 million healthcare locations spanning the globe and its combined membership accessing the healthcare network exceeds a global population of 100 million. CombiMatrix provides valuable molecular diagnostic solutions and comprehensive clinical support for the highest quality of care – specializing in miscarriage analysis, prenatal and pediatric healthcare. n

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Medical Device Daily™

Wednesday, October 9, 2013

Financings roundup

Amaranth Medical raises $20M Series B to support Fortitude A Medical Device Daily Staff Report

Amaranth Medical (Mountain View, California), a private medical device company, reported the closing of a $20 million Series B financing led by new investor DCP Management of Singapore. Existing investors Bio*One Capital, Charter Life Sciences and Phillip Capital, as well as new investor Venstar Capital, also participated in the financing. The company says that proceeds from this financing will support the continued development and upcoming CE mark clinical trial of Fortitude, a bioresorbable scaffold for use in treating coronary artery disease. “We greatly appreciate the financial support provided by DCP Management, Bio*One Capital, Charter Life Sciences, Phillip Capital and Venstar Capital, and we believe that this very successful financing is an indication of the unique potential of the Fortitude bioresorbable scaffold,” said Kamal Ramzipoor, the general manager and chief technical officer of Amaranth. “The Fortitude scaffold has been designed to have a high radial strength, significant conformability to the vessel wall and prolonged stability, yet be totally bioresorbable, which may reduce complications such as vascular inflammation, restenosis and stent thrombosis.”

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Amaranth is a spin-off company from Nanyang Technological University in 2005. The company’s Singapore facility will continue its advanced R&D activities and prepare for ramping up the production of its bioresorbable scaffold. Enrollment in the initial clinical study of Fortitude was recently completed, and preliminary results are expected to be presented at the annual Transcatheter Cardiovascular Therapeutics meeting later this month in San Francisco. “Among the recent advances in interventional cardiology, we believe that the development bioresorbable scaffolds is one of the most significant,” said Fred Schwarzer, managing partner of Charter Life Sciences and chairman of the Amaranth board of directors. “In our view, Amaranth Medical’s Fortitude scaffold has significant inherent advantages over other bioresorbable scaffolds in development, and the entire investor group is committed to supporting Kamal and the Amaranth team in the development of this important technology to improve the lives of patients worldwide.” Amaranth’s ongoing clinical study is a prospective, non-randomized, investigational study to assess the safety and feasibility of the Fortitude bioresorbable scaffold. This study enrolled patients with symptomatic coronary artery disease, and enrollment was completed in July 2013. Angiographic and intravascular ultrasound follow-up will be conducted on all study participants at six months and two years following implantation. n

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Wednesday, October 9, 2013

Medical Device Daily™

Deals roundup

Quest Diagnostics acquires ConVerge Diagnostic Services A Medical Device Daily Staff Report

Quest Diagnostics (Madison, New Jersey), a provider of diagnostic information services, reported that it has acquired ConVerge Diagnostic Services (Peabody, Massachusetts) from Water Street Healthcare Partners, a strategic investor focused exclusively on the healthcare industry. ConVerge is a leading full-service laboratory providing clinical, cytology and anatomic pathology testing services to patients, physicians and hospitals in New England. Financial terms of the transaction were not disclosed. The transaction includes ConVerge’s laboratory in Peabody and its patient service centers operating in Massachusetts, New Hampshire and Connecticut. ConVerge will operate as a wholly-owned subsidiary of Quest and its laboratory will operate as part of Quest’s national laboratory network. Over time, the ConVerge laboratory is expected to be integrated into a state-of-the-art laboratory facility Quest Diagnostics is building in Marlborough, Massachusetts. “ConVerge is our fourth laboratory acquisition this year, and the second in Massachusetts, underscoring our commitment to the state and New England,” said Steve Rusckowski, president/CEO, Quest Diagnostics. “As a regional leader in women’s health that is also recognized for customer service, medical expertise and innovation, ConVerge is a strong strategic fit with our business. The addition of ConVerge to the Quest family will extend the range of diagnostic information services patients and providers can access in the region while also combining the considerable medical leadership of both companies to spur new innovations that improve patient outcomes.” “This acquisition is consistent with our five-point strategy unveiled last year, which includes the strategy to deliver disciplined capital deployment,” said Rusckowski. “One of our capital deployment objectives is to grow one to two percent a year through strategically aligned, accretive fold-in acquisitions.” At its Investor Day conference in November 2012, Quest reported its five-point strategy to refocus on its core diagnostic information services business, drive operational excellence, restore growth, simplify the organization and deliver disciplined capital deployment. Since that time, Quest’s portfolio review has enabled the company to sell non-core assets and deliver disciplined capital deployment. Since late last year, Quest has sold its OralDNA dental diagnostics business, HemoCue diagnostic products business, Ibrutinib royalty rights and Enterix colorectalcancer product business, generating gross proceeds of approximately $800 million providing flexibility to drive shareholder value.

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In addition, the company has also now acquired four laboratory businesses in 2013. The acquisition of ConVerge is strategically aligned with Quest’s acquisition in January of UMass Memorial Medical Center’s clinical and anatomic pathology outreach laboratory businesses based in Worcester, Massachusetts. The company’s other laboratory acquisitions this year include the Tennessee-based toxicology and clinical laboratory business of Concentra, a Humana business, and lab-related clinical outreach operations of Dignity Health in California and Nevada. Quest expects the ConVerge transaction to be neutral to adjusted earnings per share in 2013 and modestly accretive to earnings per share in 2014. “We have invested our team’s industry expertise and experience to build ConVerge into a leading regional reference laboratory known for innovation and outstanding customer service,” said Jim Connelly, a partner with Water Street and a director of ConVerge. “We are pleased that the leadership of Bob Gorman and the efforts he and his team have put into expanding ConVerge’s test menu and capabilities, particularly in the area of women’s health resulted in the company being acquired by the global industry leader in diagnostic information services with the vision to build on these strengths.” In other dealmaking news, Indutrade (Kista, Sweden) reported that it signed an agreement to acquire all of the shares in Medexa Diagnostisk Service (Limhamn, Sweden), with annual sales of about $3.8 million. Medexa specializes in high-end technology for healthcare with a focus on fetal surveillance and ultrasound applications. Customers consist primarily of county councils and private clinics. Indutrade said Medexa will be part of the Industrial Components business area. The acquisition is expected to have a marginally positive impact on Indutrade’s earnings per share. n ■

Med-Tech Notes NovaBone relocates to Alachua NovaBone Products (Jacksonville, Florida), a maker of orthopedic and dental biomaterials, has begun relocation into a 30,000 square feet building in Alachua, Florida that will more than double the existing footprint of current facilities. The relocation provides more manufacturing space to support the greater than 40% sales growth the company has experienced for each of the past four years. Moreover, the relocation combines the company’s manufacturing and research & development operations under one roof, greatly improving the process of new product development and introduction. The move to the new facility has started and is expected to be completed by year end.

Wednesday, October 9, 2013

Medical Device Daily™

International report

SteriPro Canada partners with Holland Bloorview A Medical Device Daily Staff Report

SteriPro Canada (Mississauga, Ontario) has reached an agreement with Holland Bloorview Kids Rehabilitation (Toronto) hospital to manage the hospital’s Sterile Processing Services. SteriPro Canada specializes in the sterilization of reusable medical devices and will provide Holland Bloorview with services from its Mississauga facility. Holland Bloorview joins Women’s College, Humber River Hospital and Trillium Health Partners (formerly Trillium Health Centre and Credit Valley Hospital) as one of the first hospitals to take advantage of SteriPro’s facilities and services to further enhance patient care and safety. Additionally, SteriPro is providing services to community health partners (including district health units, general practitioners and surgical centers) throughout Ontario. “Our partnership with SteriPro is a prime example of Holland Bloorview’s commitment to continuous quality improvement,” said Tanya Wishloff-Hunt, Dental Operations Manager. SteriPro is Canada’s third party re-processor of reusable surgical instrumentation and medical devices. As a subsidiary of Dalkia Canada, SteriPro is aligned with Dalkia’s goals of providing responsible, efficient, environmentally and financially sustainable solutions to its partners. SteriPro offers hospitals and community healthcare providers offsite reprocessing and sterilization solutions, advisory services, and contingency services.

DaVita Missions expands Indian mission Bridge of Life – DaVita Medical Missions (Denver), a nonprofit organization dedicated to expanding dialysis and kidney care in underserved communities, reported the completion of its recent medical mission in India to upgrade the capacity of two dialysis clinics with the support from local partners, India-based DaVita NephroLife and Human Benefit Services (HBS) Trust. Bridge of Life first worked with HBS Trust in 2008 to deliver 19 dialysis machines and establish two new dialysis clinics in the Rajasthan cities of Jodhpur and Phalodi. HBS Trust continues to operate the clinics and ensures their sustainability by subsidizing treatment for people who otherwise would not be able to receive dialysis. Today, half of the machines initially installed have gone offline – either worn out due to heavy use or broken with no technician available for repairs. Bridge of Life partnered with DaVita NephroLife to evaluate existing equipment, identify and source new equipment, and provide local and responsive support while saving Bridge of Life the expenses normally used to send

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volunteers overseas. Four volunteers from DaVita NephroLife oversaw the delivery and installation of 10 machines, six of which were donated to Jodhpur and four to Phalodi. Kishore Thomas, DaVita NephroLife’s clinical service specialist, provided updated clinical and biomedical training. The new machines have increased the clinics’ current treatment capacity, and now 15 additional patients who otherwise would not have had other treatment options are able to receive care. Bridge of Life – DaVita Medical Missions, originally founded by DaVita HealthCare Partners is an independent 501(c)(3) nonprofit organization. HBS Trust are independent nonprofit organizations whose common mission is to build sustainable health care, education, and social services infrastructure in Rajasthan, India.

Australian surgeons approved for CardioCel Allied Healthcare Group (Brisbane, Australia) said an additional eight surgeons at The Prince Charles Hospital in Brisbane have been approved to use CardioCel to repair and treat heart defects in adult patients under the Authorized Prescriber Scheme (APS). “This is an important approval for Allied as it represents the first department wide team of cardiac heart surgeons to gain early access to use CardioCel for treating and repairing heart defects in adult patients. The adult market has the potential to significantly expand the market and revenue for the company considerably,” said Allied Healthcare Group CEO Lee Rodne. CardioCel recently received its CE mark in Europe for use in both children and adults. There are now 14 surgeons in Australia that are authorized to use CardioCel for the repair of heart defects with over 60 patients having successfully received the tissue implant since the initial procedure was performed. CardioCel is a cardiovascular tissue patch used to repair heart deformities including repairing and reconstructing heart valves. CardioCel has unique properties making it suited for use by surgeons as a regenerative cardiac repair tissue, as well as delivering key benefits to patients compared to existing surgical approaches. Allied Healthcare Group Limited is a diversified healthcare company focused on investing in and developing next generation technologies with world class partners, acquiring strategic assets to grow its product and service offerings and expanding revenues from its existing profitable medical sales and distribution business. Allied’s regenerative tissue engineering technology started as a research program in 2001 focusing on tissue engineering and regenerative medicine based around the proprietary ADAPT Tissue Engineering Process. The lead program CardioCel has successfully completed a number of animal studies and a Phase II human clinical trial. CardioCel is a cardiovascular patch used to repair pediatric heart deformities. n

Wednesday, October 9, 2013

Aptus

Medical Device Daily™

Continued from Page 1 implanted with a stent graft years before. Due to the ongoing progression of the disease that’s come back these patients might have leak or migration and need to be retreated. “This is data coming from our ANCHOR post-market registry and its very much in line with our vision and where we’re trying to head as a company,” James Reinstein, president/CEO of Aptus Endosystems, told Medical Device Daily. “We are an adjunct procedure to the repair of AAA aneurysm. Our vision is to replicate the gold standard of aneurysm repair, which is surgical repair. This is the first cut of the data. This is the first time the core lab had gotten the visual images of the patients that had been enrolled.” Reinstein added, “this first set of data demonstrates that we are treating the patients that tend to come back for secondary interventions. This first set of data really speaks to what the success is of the Heli-FX Anchor.” Initial results from the registry showed acute safety and efficacy results with the device. Results also show that all acute Type 1a endoleaks were successfully resolved in Primary group. Procedural success was achieved in 99% of the Primaries and in 90% of Revisons. Type Ia endoleaks were absent at 1-month in 96% of Primaries and 91% of Revisions. “I think that although it’s early, the first set of data demonstrates that we’re heading in the right direction with our vision,” he said. The company received FDA approval for the Heli-FX system nearly two years ago (Medical Device Daily, Nov. 23, 2011). The Heli-FX EndoAnchor System is a mechanical fastening device that is designed to enhance the longterm durability and reduce the risk of repeat interventions in EVAR. By deploying small helical screws to connect the graft to the aorta, Heli-FX seeks to provide a permanent seal and fixation, similar to the stability achieved in an open surgical anastomosis. The Heli-FX system can be used during primary EVAR procedures to enhance an endograft’s inherent fixation and sealing mechanisms. It can also be used to repair endovascular grafts that have developed endoleaks, migrated away from the implant site, or are at risk of developing these complications, which are often seen after EVAR. “We’ve had what I consider very significant and rapid enrollment,” he said. “It was way ahead of what we were planning quite frankly, as a start-up company that watches every nickel. We were very surprised by the number of patients that were getting enrolled.” But high enrollment is a testament to the fact that AAA treatment is a strong market. It is estimated that 1.5 million Americans have AAA, and an estimated 200,000 people in the U.S. and 100,000 people in Europe are diagnosed with

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AAA each year. “The ANCHOR registry has been enrolling fast thanks to strong support from our physicians, and we are pleased to share these initial, early results,” Reinstein said. “Especially interesting has been the high percentage of patients who have received Heli-FX prophylactically, showing that in the real world setting, physicians are concerned with the long term results of patients who have difficult proximal neck anatomy.” Last year, the company reported closing on $25 million of equity financing (MDD June 28, 2012). Synergy Life Science Partners, a new investor, led the round and was joined by existing investors US Venture Partners and Longitude Capital Management.■ Omar Ford; 770-810-3125 omar.ford@thomsonreuters.com

Patent watch

Asuragen gains patent for detection of miR-21 A Medical Device Daily Staff Report

Asuragen (Austin), a company focused on using genomics to drive better patient management, said that the U.S. Patent and Trademark Office (USPTO) has issued a Notice of Allowance for U.S. Patent Application No. 12/890,398 with claims covering the detection of miR-21 across all cancers and for all sample types. “Overexpression of miR-21 has been widely associated with cancer in lung, colorectal, prostate and thyroid among others and is a therapeutic target being pursued by a number of biotechnology and pharmaceutical companies,” commented Rollie Carlson, president/CEO of Asuragen. “This recent patent allowance complements our growing portfolio of issued miRNA patents and provides a foundation to support our development of miR-21-based diagnostic panels and an opportunity to collaborate with external partners.” miR-21 is over-expressed in almost all solid tumors including breast, colon, esophageal, head and neck, lung, pancreas, prostate, and stomach cancers. It is the only miRNA that is up regulated in nearly all classes of human cancers derived from connective tissues and epithelial, hematopoietic, germ or nervous cells. Further supporting the ubiquitous oncogenic role of miR-21, multiple scientific publications have shown that miR-21 plays an important role in virtually every cellular process involved in tumor development such as proliferation, angiogenesis, replicative immortalization, invasion and metastasis, genome instability and mutation, tumorpromoting inflammation, deregulation of cellular metabolism, evading growth suppressors, immune destruction and cell death. ■

Wednesday, October 9, 2013

Medical Device Daily™

EndoGastric

Continued from Page 1 Nine participating U.S. hospitals have enrolled and treated 129 patients since the RESPECT study began in June 2011. The investigators, consisting of 15 general surgeons and a gastroenterologist, will follow the patients for 12 months. Initial reported outcomes may begin to be presented at scientific meetings as early as 2014, the company noted. Adrian Lobontiu, MD, medical director at EndoGastric, told Medical Device Daily that the patients enrolled in this study were patients who suffered from GERD symptoms despite PPI therapy. “They are not happy, their symptoms are still there, they do not want to go to a more invasive procedure,” Lobontiu said, describing the patients’ status prior to enrollment. The study was designed so that patients in the treatment arm will be off PPI therapy and sham patients will be on PPI therapy, some even taking a double dose of the PPIs. “By designing the study in this way we have a really, really strong study, well designed, that will give a real level one evidence comparing how” effective the TIF procedure is. Prior to joining EndoGastric Solutions in the U.S., Lobontiu was based in Paris, France where he managed the company’s European business at EndoGastric Solutions Europe and has been performing the TIF procedure since 2005. To date, he has performed or proctored over 1,000 TIF procedures. “I saw those patients when I was based in France where my practice is and they are really desperate,” he told MDD, describing the patients who are on PPI therapy but still suffering from the symptoms of GERD. “They don’t know what to do, they continue to take their PPIs, they go on double dose, maximum dose of PPIs . . . the symptoms just don’t go away. There is a gap in the treatment of GERD [for] these patients and [with] this procedure, we are here to fill that gap and to give these patients another option to be treated.” Of the patients he treated in France with the TIF procedure, Lobontiu said those patients at follow-up appointments are generally “really, really, happy.” GERD is a condition caused by anatomical changes where the muscle at the base of the esophagus relaxes between swallows, allowing corrosive stomach acid to wash back up into the esophagus. The stomach produces hydrochloric acid after a meal to aid in the digestion of food. The cells that line the stomach consists of protective mucus that protect it from erosion, but the lining of the esophagus does not share these resistant features and stomach acid can damage it. “It’s a really, really effective procedure,” Lobontiu said. The EsophyX device was FDA cleared in 2007, and is commercially available in the U.S. Inserted transorally with visual guidance from an endoscope, the EsophyX device is used in the TIF procedure to reconstruct the gastroesophageal valve (GEV), restoring its competency and reestablishing the barrier to reflux. The TIF procedure

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is a surgical solution that corrects the root cause of GERD. The TIF procedure is based on traditional surgical principles and offers similar effectiveness to a surgical repair with the safety profile of an incision-free approach. To date, more than 14,000 patients have been treated worldwide. “We are thrilled to complete enrollment and primary treatment of over 120 patients in the RESPECT trial, which compares PPI with TIF, in a randomized, blinded fashion. Only after six months are patients able to know whether or not they have had the TIF performed,” said John Hunter, MD, Mackenzie Professor & Chairman of Surgery at Oregon Health & Science University (Portland). “We are excited to ‘un-blind’ the data, and begin to determine in a very objective fashion the benefit that the TIF procedure might provide when compared to PPIs.” Hunter and Peter Kahrilas, MD, professor of medicinegastroenterology at Northwestern University (Evanston, Illinois) are co-principal investigators in the trial. RESPECT is the first randomized trial evaluating transoral fundoplication against both a sham procedure and PPI therapy, and includes PPI-dependent GERD patients suffering from breakthrough moderate-to-severe symptoms at least two to three times a week. “GERD is a progressive disease that patients learn to manage with lifestyle changes and calibrated medication dosing. Once these treatment options are exhausted or when they prove unsatisfying, procedural interventions or surgery become their best hope to control symptoms,” Kahrilas said. “The RESPECT study will help define the appropriate selection criteria for patients who will most likely benefit from the TIF procedure and experience an improvement in their quality of life.” The primary goal of the study is to determine if at sixmonth follow up the TIF procedure leads to a clinically significant reduction in GERD symptoms, specifically “troublesome” regurgitation with or without heartburn as defined by the Montreal Consensus. Investigators will also determine if the patients’ esophageal acid exposure has normalized and measure the degree to which reflux esophagitis has healed after six months and after one year. “Conducting a randomized trial that includes a sham treatment arm is a significant endeavor. We would like to thank all the individuals who have worked so hard to make this trial happen,” said Michael Kleine, president/CEO of EndoGastric Solutions. “We have an enormous debt of gratitude to the many patients who entered this trial. Their willingness to participate in a study despite uncertainty of their initial treatment is to be commended.” Lobontiu also noted that the TIF procedure typically takes less time than the standard surgical approach for GERD, is easier to use, delivers consistent results, and is less invasive. n Amanda Pedersen, 912-660-2282; amanda.pedersen@thomsonreuters.com

Wednesday, October 9, 2013

Israel

Medical Device Daily™

Continued from Page 1 now being designed between Israel and Far Eastern groups – in our two-part note Japan and China. In this article and the next, we will address some of these new moves, and see how Israeli innovation and out-of-the-box thinking is attracting Eastern promise. Two breakthrough technologies recently found their first strategic partnerships in Japan. Brainsway (Jerusalem) is focused on developing and marketing of Deep TMS (Transcranial Magnetic Stimulation) systems, for treatment of a wide range of neurological and psychopathological disorders, using magnetic coil technologies licensed from the National Institutes of Health (Bethesda, Maryland). In January, the FDA approved the use of Brainsway’s proprietary Deep TMS device for the treatment of depression in medication-refractory patients. As a result of this approval, last month, Brainsway and Century Medical, a subsidiary of Itochu (both of Tokyo), signed a distribution/ marketing agreement. Initially the agreement covers the FDA-approved Major Depressive Disorder condition, but it contains an option to use this platform for other Brainswayresearched disorders too. While depression is the initial target application for the Japanese group, as additional clinical data appears for many other brain disorders, Century will have rights towards these large markets too. In July, the company received European CE approval for use of their Deep TMS device for a wide range of conditions, which may lead both Brainsway and Century to a further expanded patient set. It is rare for a devices company with 2012 sales of less than $500,000 to close such an agreement with a significant Japanese player. “This further indicates how the East is not planning to be left behind with potentially transformational technologies, even when these are not yet an established brand in the West,” one analyst told Medical Device Daily. A second indication from Japan of the quality of technology that they see coming from Israel, is the recent collaboration between Japanese robotics giant Yaskawa (Kitakyushu) and Israel’s Argo Medical Technologies (Yokneam). Last month, Argo signed a strategic distribution agreement with Yaskawa (the Japanese group’s first Israeli medical investment) for its ReWalk Exoskeleton system. The company’s product uses patented technology with motorized legs that power knee and hip movement. Battery-powered for all-day use, ReWalk is controlled by on-board computers and motion sensors, restoring selfinitiated walking without needing tethers or switches to begin stepping. Yaskawa, a conglomerate with a turnover of over $1 billion in its Robotics division (36% of 2012 sales) has committed both collaborative support and equity funding from this group as part of the latest round of financing. “Existing investors, including SVP Vitalife and Israel Healthcare Ventures (both of Tel Aviv) and Pontifax (Herzliyya) participated, but Yaskawa was the largest

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investor in the latest round,” Larry Jasinski, Argo’s CEO, shared with MDD, “which should take Argo through to break even in 2015”. A major element here, though, is Yaskawa’s approach to leveraging Argo as a marketing partner in the West, possibly based on Jasinski’s extensive sales experience in the U.S. Yaskawa has proposed that in addition to the Argo ReWalk system – the first medical robotic product that they are marketing – Yaskawa will engage Argo to market Yaskawa’s proprietary medical robotic pipeline to the Western world in the next few years. “Our relationship has grown out of strength of both sides,” Jasinski explained. “We offer them a well-proven and revolutionary product, as well as a channel – which their current investment is supporting – that they have no interest in replicating in America and Europe.” The ReWalk product is already selling in Europe and Canada, and is expected to receive FDA approval as a result of a threeyear safety study on 28 patients, in the coming months.

A big deal for many pharma startups Another large Japan-related deal that was announced in Israel last month. Israel’s Office of the Chief Scientist’s Biotech Incubator Tender. For this project, the Israeli government issued guidelines for global pharmaceutical players to collaborate with Israeli (financial) players, in order to have a local presence, but with a global approach to the next generation of Israeli biopharma startups. The Israeli government wants to offer startups the experience, management approaches and discipline associated with the global pharma R&D environment. The terms of the tender therefore requested the marriage of local and global aspects, in order to help select optimal projects for government incubator backing, and particularly to enhance Israel’s competitiveness in this complex and expensive pharma environment. The tender offer required a three-way partnership between the Israeli sponsor, the global sponsors and the Israeli government, to ensure significant funding per project for a period well beyond the two-to-three year time-span that characterizes the classic Israeli Incubator model. “For them to feel comfortable with the possibility of this incubator being a turning point in the world of Israeli pharma, the government needed partners with deep pockets and the patience for longer periods of incubation” a source close to the project shared with MDD. While the government received an offer from a consortium including AstraZeneca (London) as the pharma partner, the winning team consisted of Johnson and Johnson (New Brunswick, New Jersey) and Takeda Pharmaceuticals (Tokyo, Japan) partnering with Orbimed Israel (Herzliyya) as a local financial presence. Takeda has not played a significant role in the Israeli bio-startup scene in the past. The winds are changing when a serious Japanese player of this magnitude (albeit with a large U.S.See Israel, Page 10

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Medical Device Daily™

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Continued from Page 1 Daily, Sept. 12, 2013). CorPak Medsystems (Buffalo Grove, Illinois) also received a warning letter citing definitional issues such as the meaning of “reasonably suggests” (MDD, May 1, 2013), a series of developments hinting that the agency saw a serious problem with industry’s understanding of the language of regulations. The draft tackles the meaning of “become aware of” by noting that the term is in force whenever a device maker’s employee “becomes aware of information that reasonably suggests that an event is required to be reported” in a 30day or five-day report. Also included in this section is that the term applies when employees become aware “from any information” – including trend analyses – that an event “necessitates remedial action to prevent unreasonable risk of substantial harm to the public health.” However, much of this verbiage is reflected in 21 CFR 803.53. The expression “reasonably suggests” is explained in the draft as meaning that any information, including “scientific, or medical facts, observations or opinions” that would lead to “a reasonable conclusion that a device has caused or may have caused or contributed” to a reportable event. Here, too, trend analyses qualify as a source of qualifying information. The exception here is that the available information would “lead a person who is qualified to make a medical judgment to reasonably conclude” that the device in question “did not cause or contribute to a death or serious injury.” In a question-and-answer portion of the draft, FDA states that a manufacturer “should submit a separate report for each suspect device” in the reportable event, including when it is not possible to determine which device “actually caused or contributed to the event.” MedLogiq (Pune, India), a provider of medical data services, provided the only available comment for the record that was not posted anonymously, making the argument that the agency should require industry to “research, develop and implement ‘state of the art’ technologies and solutions to identify and resolve quality or performance issues in the most expedient manner possible.” William Acevedo, MedLogiq’s CEO, asserted that the MDR process should include a mechanism to identify “precursor events,” such as component and engineering changes. He also urged that FDA take steps to “ensure regulations are not simply perceived as a hurdle for medical device manufacturers to clear.” He also stated that outsourcing of manufacturing operations suggests a need for continuous testing plans, among other features. Acevedo claimed that other industries have adopted advanced quality management techniques, adding that adverse event reports “and regulatory actions continue to rise at alarming rates.”

SCOTUS eyes Stengel preemption case The Supreme Court of the U.S. has invited the Solicitor General of the U.S. to file a brief in the case of Stengel v.

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Medtronic, another test of FDA’s preemption of state law for PMA devices, and another such case involving Medtronic (Minneapolis), which seems to be the primary target in a conspicuous percentage of such lawsuits. Medtronic lost to Richard and Mary Lou Stengel at an en banc hearing in the U.S. Ninth Appeals Court earlier this year (Medical Device Daily, Jan. 22, 2013), although the firm was successful in the first hearing at Ninth Appeals. The full panel at this court, however, invoked Medtronic v. Lohr, the 510(k) preemption case, in asserting that the Supreme Court decision in that case “was an across-the-board holding,” a claim that would likely be disputed. Medtronic, which filed for a review at the high court in May, says in its request for a Supreme Court review that the central issue is whether the Medical Device Amendments of 1976 preempt “a state-law claim alleging that a medical device manufacturer violated a duty under federal law to report adverse-event information to the FDA.” The company argued that a Supreme Court review is indicated due to a split among circuit courts, citing the case involving the Sprint Fidelis lead as an example of a case that revolved in part around the question of adverse event reports. However, the company’s argument is also that the decision at the en banc hearing at Ninth Appeals “effectively nullifies this Court’s decisions in Buckman and Riegel.” Medtronic’s argument is further that the Ninth Appeals decision “held that state tort claims are not preempted whenever the plaintiff invokes a generalized common-law duty of care to enforce federal requirements – even if state law would not independently impose the duty in question in the absence of” the statute. Ergo, Medtronic argues, that decision “effectively creates a private right of action to enforce” the Medical Device Amendments. Medtronic said that resolution “of these conflicts is exceptionally important,” noting that the outcome at Ninth Appeals “would subject medical device manufacturers to potentially irreconcilable state and federal regulatory requirements because juries would be empowered to impose liability even for conduct that the FDA has found does not violate the MDA.” The predicament “also would subject medical device manufacturers to substantial sanctions for MDA violations that federal regulators have chosen to address through different, more finely calibrated means,” Medtronic adds, a scenario that would “complicate substantially the task of bringing new, potentially lifesaving medical devices to market through the imposition of unpredictable costs and open-ended liability.” The Washington Legal Foundation (WLF; Washington) also weighed in with a June 13 statement to the Court, asserting that the claims made by the Stengels “present precisely the same types of conflicts with federal policy” as those seen in Buckman. WLF’s Richard Samp commented further that the outcome in Ninth Appeals “authorizes juries to second-guess any manufacturer interaction with FDA that post-dates product approval.” n

Wednesday, October 9, 2013

Medical Device Daily™

Product Briefs • Biotronik (Lake Oswego, Oregon), a maker of cardiovascular technology, has completed patient enrollment in the iliac arm of its BIOFLEX-I trial. The trial is a prospective, non-randomized, multi-center IDE study consisting of two arms: SFA (superficial femoral artery) and iliac. Alongside ongoing enrollment in the SFA arm, the newly completed iliac arm evaluates the use of the Astron stent in the treatment of common or external iliac artery lesions. Astron is CE-marked and commercially available in over 50 countries worldwide. Astron stents were implanted in 160 patients at 34 centers in the U.S. and Europe, completing enrollment in the iliac arm of the BIOFLEX-I trial. • Devon Medical (King of Prussia, Pennsylvania), maker of the extriCARE portable Negative Pressure Wound Therapy (NPWT) System, reported the availability of its foot NPWT dressing for treatment of non-healing wounds on the toes and forefoot. The dressing kit comprises a spoon-shaped nonwoven dressing pad, a transparent polyurethane skin drape, an adhesive polyurethane suction bell with connection tubing, a silicone gel strip pack, and four nonwoven dressings for use between the toes. Caregivers may use antifungal ointment or powder between the toes and petroleum jelly or ointment on the toenails to prevent them from adhering to the skin drape. Devon Medical has developed various NPWT dressings, including three sizes of oval dressings, a sacral dressing, and an incisional dressing. • Sanuwave (Alpharetta, Georgia) has enrolled 50% of the minimum required patients in the Phase III supplemental clinical trial evaluating the dermaPACE device on patients with diabetic foot ulcers. The clinical trial is designed to enroll a minimum of 90 patients and is on-track for completion in the first quarter of 2014. The on-going Phase III clinical trial has enrolled 45 of the 90 minimum required patients needed to evaluate the safety and efficacy of dermaPACE in treating patients with diabetic foot ulcers. The trial is designed to establish superiority in diabetic

Israel

Continued from Page 8 based franchise from its 2008 Millennium Pharmaceuticals acquisition) decides to wade into Israel’s environment with this high-profile long-term commitment. Beyond the strategic connections and added valued in terms of experienced new board members, early stage companies that are accepted into the incubator will benefit from funding of at least NIS 8.1 million (~$2.3 million) for the first three years activity, with 85% coming from government funds. In the next article we report on news regarding similar links that are forming between Israel and China, in particular in the big business of industry-guided academic collaboration. n

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foot ulcer healing rates using the dermaPACE treatments as compared with the control group, when both are combined with standard of care dressings and with offloading from a walking boot as required. Treatment consists of four noninvasive procedures during the first two weeks, and up to four (4) additional non-invasive procedures delivered biweekly between weeks 4 and 10. The primary endpoint is complete wound closure at 12 weeks. Sanuwave Health is a shock wave technology company that makes devices for the repair and regeneration of skin, musculoskeletal tissue and vascular structures.

People in the News • CAS Medical Systems (CASMED; Branford, Connecticut) has named Brian Wagner as chief commercial officer. Most recently, Wagner was senior VP and chief marketing officer for Philips Imaging Systems. CASMED makes medical devices for non-invasive patient monitoring. • MolecularHealth (The Woodlands, Texas) has hired Laura Housman as chief commercial officer. Most recently, Housman was VP of global market access, pricing and health economics at Novartis Pharmaceuticals’ Molecular Diagnostics (MDx) and Genoptix. MolecularHealth says it provides doctors and patients with faster, more accurate insights into the role genes play in the progression and treatment of an individual’s cancer. • Premier (Charlotte, North Carolina) has named Jim Storey as VP of investor relations. Most recently, Storey was director of investor relations and corporate communications for Horizon Lines. Premier is a healthcare performance improvement alliance. • Pulse Systems (Concord, California) reported the recent addition of two key personnel, further strengthening the company’s position in the precision metal fabrication segment of the medical device contract manufacturing industry. Joining the company as director of operations, Brett Poole brings his years of experience in manufacturing management and customer service to his new position. Prior to joining Pulse, Poole was GM of Fusion Composites. Also joining Pulse Systems is Wen Ho, PhD, as senior manufacturing engineer for laser processing. Ho previously was employed by Abbott Vascular. Pulse Systems provides precision laser machining of tubular metal components for the medical device industry, including implantable devices such as endovascular stents. • SynapDx (Lexington, Massachusetts) said Kevin Hrusovsky has been named to its board of directors. Hrusovsky, former president of Life Sciences and Technology at PerkinElmer, has a breadth of experience in launching technologies and building fast-growing companies in the life science industry. SynapDx is a diagnostic company developing an innovative blood test for the early detection of autism spectrum disorders.

MDD’s Oncology Extra ADDITIONAL DEVELOPMENTS

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Keeping you up to date on recent developments in oncology Study raises more questions about PSA test . . .

The U.S. Public Services Task Force recommended in 2008 that men aged 75 and older not be screened for prostate cancer, but a recent study coming out of Yale University (New Haven, Connecticut) indicates that the U.S. government is still spending to screen this population for prostate cancer. Of perhaps greater interest to epidemiologists, however, is the fact that the study suggests that increased screening does little to bolster the rate of diagnosis of metastatic tumors. The statement claims that of the nearly $450 million spent annually by Medicare on PSA tests, roughly a third was on screening for gents who have hit their dodranscentennial, a claim arrived at by the authors of the study working at the Yale Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center. Also of interest in this context is that the researchers “found that the costs of prostate cancer screening ranged considerably from $17 to $62 per beneficiary across regions,” the statement claims, noting also that most of the variation “was not due to the cost of PSA test itself, but rather to variation in costs of the follow-up tests across regions.” The study, which can be seen in Cancer, was an observational effort which followed an unspecified number of men on Medicare who received a clean bill of health in 2006 and were followed for three years. Lead author Xiaomei Ma, PhD, an associate professor at Yale School of Public Health, and her colleagues also found that the data were iffy where the benefits of screening and treatment are concerned. The statement explains that while men living in high-spending regions “were more likely to be diagnosed with localized cancers, they were not significantly less likely to be diagnosed with metastatic cancer,” a signal suggestive of the possibility that “spending more on prostate cancer screening might identify more localized tumors, but may not necessarily reduce the rate of metastatic cancers.” Cary Gross, MD, a professor of internal medicine at Yale School of Medicine, remarked, “in terms of what these results mean for Medicare spending, this is just the tip of the iceberg.” Gros said many older men diagnosed with early-stage prostate cancer “may end up receiving therapy that is potentially toxic, has little chance of benefit, and carries substantial cost. In order to truly understand the costs of screening, the next step is to identify how many additional cancers are being diagnosed and treated as a result of screening older men for prostate cancer. We need better tools to target screening efforts towards those who are likely to benefit,” Gross said.

Authors propose nipple as entry point for drugs . . . As excruciatingly uncomfortable as it sounds, researchers at Harvard Medical School (Boston) have commenced with research into the use of the human nipple as an entry point for treatments for some breast cancers. To date, the procedure has been employed in mice, and the statement points out that this approach “offers direct access to the most common origin of breast cancer, the milk ducts,” and because of that, it “could be used to offer cancer therapy that spares healthy regions of the body.” Silva Krause, PhD, of Harvard Medical, noted that this effort entails the injection of a new nanoparticle-based agent intended to inhibit an unspecified gene known to trigger breast cancers. Krause remarked that this localized delivery of a therapeutic agent “could diminish the side effects typically observed with systemic chemotherapy” thanks to the fact that most of the body is spared exposure to the chemotherapy. However, administering an agent this directly “also prevents drug breakdown by the liver, for example, which can rapidly reduce effective drug levels,” Krause commented. The results of this effort appear in the Journal of Visualized Experiments. Langone snares $6.25M grant for ALL . . . The poignancy of childhood cancers is tough to ignore, and the New York University School of Medicine (New York) announced recently that its Langone Medical Center has snared a grant of $6.25 million to take on acute lymphoblastic leukemia (ALL), said to be the most common childhood cancer. The grant, which funds these efforts from Oct. 1 to Sept. 20, 2018, is said to address “four separate research projects spanning six institutions that unite around a common goal: finding targeted treatments for ALL patients who relapse and derive no benefit from existTo subscribe, please call MEDICAL DEVICE DAILY™ Customer Service at (800) 477-6307; outside the U.S. and Canada, call (770) 810-3144. Copyright © 2013 Thomson Reuters. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com.

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ing chemotherapies.” Langone will serve as the site for two of the four efforts, one of which will take up the issue of drug resistance in refractory ALL patients while the second will work toward new drugs designed to “target the cellular cycle of ALL cancer cells.” The remaining two efforts, which will be housed in other institutions, will work toward identifying and correcting genetic mutations in ALL cancer cells, and develop nanoparticle therapies for treatment of ALL. The Leukemia & Lymphoma Society (Alexandria, Virginia) is the source of the jingle funding all this research into a disease group that affects roughly 6,000 children each year in the U.S. The statement points out that the cure rate for children with ALL “has increased to nearly 80% in the past four decades,” but Willam Carroll, MD, of Langone remarked, “the prognosis is still dismal for patients who relapse. Through this powerful collaboration, we intend to change that.”

Merging of gene databases yielding insights . . . The number of projects designed to catalogue the human genome has mushroomed over the past few years, and while these projects have individually led to some major milestones, researchers at Yale University (New Haven, Connecticut) believe that combining those databases might render even more fundamental insights into the mechanisms of cancer. The Yale statement notes that the 1000 Genomes project has generated data on “regions of DNA that vary little within the population and thus are of crucial importance to human health,” while the Encyclopedia of DNA Elements (ENCODE) project is “cataloguing the function of each location in the human genome.” The team involved in this meta-analytical effort drew on non-protein coding DNA elements from the ENCODE project and cross-checked for this “that are highly conserved in the 1000 Genomes data,” the statement explains. These were checked against data on mutations in tumor samples from roughly 90 patients with breast or prostate cancer, and the researchers “found dozens in areas of DNA that vary little and therefore are likely to drive tumor progression.” The researchers “also looked for additional features of the cancer mutations such as their proximity to regulatory-network hubs, which also indicate they may be particularly damaging,” the statement notes. Senior author Mark Gerstein, PhD, said this tack “allows us to take a systematic approach to cancer genomics,” remarking, “now we do not need to limit ourselves to the roughly 1% of the genome that codes for proteins but can explore the rest of our DNA,” the so-called junk DNA. The results of this analysis appear in the Oct. 4 edition of Science. Study suggests PET predicts lung cancer outcomes . . . Doctors like radiology devices and policymakers are not so sure, but a statement by University Hospitals Case Medical Center (Cleveland) says that a multi-site trial demonstrated that PET “shows great promise in predicting which patients with inoperable lung cancer have more aggressive tumors and need additional treatment.” The statement notes that the National Cancer Institute-funded trial had enrolled 250 patients at 60 cancer centers around the U.S., offering PET scans to stage III lung cancer patients “before and after a combined treatment regimen of chemotherapy and radiation therapy.” The scans were performed to measure the rate of uptake of FDG, and the researchers are said to have discovered that post-treatment scans were “predictive for patients’ prognosis by identifying that patients with high levels of FDG uptake following treatment had more aggressive tumors that were more likely to recur.” The numbers also suggest that higher uptake values in primary tumors correlated directly with more frequent recurrence and lower survival. Also of some significance is that a “strong correlation” was evident “between the radiation dose intensity and local control of the cancer, indicating that further research needs to be conducted in radiation technology for lung cancer.” Case’s Mitch Machtay, MD, said the findings “have the potential to give cancer physicians a new tool to more effectively tailor treatments for patients with locally advanced lung cancer,” — Compiled by Mark McCarty, MDD Washington Editor mark.mccarty@thomsonreuters.com

To subscribe, please call MEDICAL DEVICE DAILY™ Customer Service at (800) 477-6307; outside the U.S. and Canada, call (770) 810-3144. Copyright © 2013 Thomson Reuters. Reproduction is strictly prohibited. Visit our web site at www.medicaldevicedaily.com.