Coronary Aneurysm

—The first RCT comparing use of site-specific antithrombotic drug therapy with two anticoagulants and an anti-proliferative mTOR inhibitor versus traditional drug-eluting stent— —Primary endpoint of Target Lesion Failure (TLF) was met, supports safety and effectiveness of on-device, site-specific antithrombotic drugs combined with anti-proliferative agent designed to reduce device thrombosis risk— SAN FRANCISCO--(BUSINESS WIRE)-- Elixir Medical, a developer of novel cardiovascular technologies, today announced positive six-month clinical data from the DESyne BDS Plus Randomized Controlled Trial (RCT) evaluating DESyne BDS Plus, the world’s first triple drug-eluting coronary implant with site-specific delivery of antithrombotic drugs versus a second-generation, durable polymer drug-eluting stent (DES). The study met its primary endpoint of target lesion failure (TLF) with no TLF events reported in the study arm, demonstrating safety compared to DES. The data were presented by Stefan Verheye, M.D., Ph.D., Interventional Cardiologist at ZNA Cardiovascular Center in Antwerp, Belgium and the study co-principal investigator at the Innovation Program session at the Transcatheter Cardiovascular Therapeutics (TCT) conference today in San Francisco. “Early (<30 days) and especially acute and subacute stent thrombosis is a major catastrophic event with high rate of in-hospital mortality and myocardial infarction (MI) and a significantly increased risk of major adverse cardiac events out to 5 years. Furthermore, balancing ischemic and bleeding risk when using guideline-directed dual antiplatelet therapy (DAPT) in patients at high thrombotic risk and high bleeding risk often requires a compromise,” said Stefen Verheye, M.D., Ph.D. “These data from the DESyne BDS Plus RCT give hope that site-specific antithrombotic therapy may offer additional protection for our patients and eliminate the tradeoff decisions associated with oral antithrombotic therapy in the future.” Clinical results The study’s primary endpoint was met (pnon-inferiority<0.001); TLF rate at day three or at hospital discharge, whichever came first, was 0.0% for DESyne BDS Plus versus 5.0% (95%CI, -11.8% to 1.8%) with the durable polymer DES. At six months, TLF rate was 1.0% for DESyne BDS Plus and 8.2% (p=0.035; 95%CI, -14.8% to -1.3%) for the durable polymer DES. No definite or probable stent thrombosis, target vessel myocardial infarction or cardiovascular deaths were observed with DESyne BDS Plus study device. At six months, target-vessel myocardial infarction rates were significantly lower in the DESyne BDS Plus group (0%) compared to the durable polymer DES (6.3%). The secondary endpoint, in-device late lumen loss (LLL) at six-months was similar between both devices; 0.14±0.05 mm in the DESyne BDS Plus group and 0.09±0.05 mm in the durable polymer DES. A live case of 12-month imaging follow-up of one of the patients will also be presented by Alexandre Abizaid, M.D., Ph.D., Interventional Cardiologist at Instituto do Coracao (InCor) in Sao Paulo, Brazil and Carlos Campos, M.D., Ph.D., Interventional Cardiologist at Heart Institute (InCor) in Sao Paulo, Brazil at the Live Case Sessions - Coronary Artery Disease V at the TCT conference today. “DESyne BDS Plus is the first stent that combines an antiproliferative inhibitor with two anticoagulant drugs,” said Alexandre Abizaid, M.D., Ph.D. “This combination of triple drug site-specific antithrombotic therapy with an initial release in the beginning—which is very important in the acute phase—and a sustained release has the potential to impact the way we treat patients at high thrombotic risk and high bleeding risk in the future.” Coronary artery disease is the leading cause of death for men and women in most racial and ethnic groups in the U.S.1 While PCI has positively impacted mortality rates2, procedure and device related risks remain. Stent thrombosis after PCI is associated with large territory myocardial infarction (MI) events and poor outcomes, with death rates as high as 50% for early (<30 days) thrombosis cases3. Management of ischemic and thrombotic risk requires medication adherence, but only 60% of patients are adherent to their prescribed cardiovascular medications which can lead to an increased risk of cardiovascular events or mortality by 20% or 35%, respectively.4 In addition, 3.5% of patients undergo non-cardiac surgery within six months of PCI procedure requiring careful management of thrombotic and bleeding risk5. “Our novel DESyne BDS Plus platform leverages triple drug site-specific antithrombotic therapy (TRx) designed to reduce clotting risk at the site of the implant without increasing the bleeding risk associated with systemic oral antithrombotics, thereby simplifying the complexity of patient management, and potentially improving outcomes and making timely PCI therapy a safer option for more patients,” said Motasim Sirhan, CEO of Elixir Medical. “We are excited by these data from the DESyne BDS Plus RCT as we build a growing body of clinical evidence supporting all of our innovative devices.” DESyne BDS Plus device has a bioresorbable coating with three drugs: two anticoagulants (rivaroxaban and argatroban) and an antiproliferative mTOR inhibitor (sirolimus). The coronary implant is designed to help manage thrombotic and bleeding risk for at-risk PCI patient populations. The DESyne BDS Plus RCT is a prospective, multicenter, randomized, single-blind study of 202 patients across 14 sites. Angiographic and OCT imaging was conducted on approximately 60 patients in both arms to assess and document six-month results for late lumen loss (0.14±0.05mm in DESyne BDS Plus versus 0.09±0.05mm in the durable polymer DES) and diameter stenosis (11.3±6.2% in DESyne BDS Plus versus 12.3±6.3% in the durable polymer DES). Preclinical studies with DESyne BDS Plus device have shown site-specific tissue therapeutic levels of anticoagulants for up to one year after device implantation while systemic blood levels of anticoagulants were sub-therapeutic. A pharmacokinetic clinical sub-study was conducted to assess the blood pharmacokinetics of sirolimus, rivaroxaban and argatroban eluted from the DESyne BDS Plus device after implantation. The sub-study validated sub-therapeutic systemic blood concentration levels of both anticoagulants confirming that the DESyne BDS Plus device with its site-specific delivery of antithrombotic drugs does not present a systemic dose risk. About Elixir Medical Elixir Medical Corporation, a privately-held company based in Milpitas, California, develops disruptive platforms to treat coronary and peripheral artery disease. Our technologies have multiple applications across the cardiovascular space capable of delivering improved clinical outcomes for millions of patients. Visit us at and on LinkedIn. About the DESyne BDS Trial The DESyne BDS Plus Randomized Clinical Trial (RCT) is a prospective, multicenter, single-blind study evaluating the safety, effectiveness, and performance of the DESyne BDS Plus Triple Drug-Eluting Coronary Implant compared to DESyne X2 Drug-Eluting Coronary Stent System in the treatment of de novo native coronary artery lesions. The trial includes 202 patients across 14 sites in Europe, New Zealand and Brazil. An imaging subset of 58 patients had angiographic and optical coherence tomography (OCT) assessment completed in the first six months. Data collection will continue through three years. About TRx TRx is the world’s first triple-drug site-specific antithrombotic therapy using two anticoagulants (rivaroxaban and argatroban) and an antiproliferative mTOR inhibitor, sirolimus. The therapy was designed to address challenges associated with percutaneous coronary intervention (PCI), including management of thrombotic and bleeding risk. References: 1. Heart Disease Facts | CDC.gov. (2023, May 15). Centers for Disease Control and Prevention. 2. Liza Chacko, James P. Howard, Christopher Rajkumar, Alexandra N. Nowbar, Christopher Kane, Dina Mahdi, Michael Foley, Matthew Shun-Shin, Graham Cole, Sayan Sen, Rasha Al-Lamee, Darrel P. Francis and Yousif Ahmad, Effects of Percutaneous Coronary Intervention on Death and Myocardial Infarction Stratified by Stable and Unstable Coronary Artery Disease: A Meta-Analysis of Randomized Controlled Trials, Cardiovascular Quality and Outcomes. 2020 3. Lawton et al. 2021 ACC/AHA/SCAI Coronary Revascularization Guideline. 4. Chen Chen, MD, 1 Xiaoqing Li, MD, 1 Yuhao Su, MD, 1 Zhigang You, MD, PhD, 1 Rong Wan, PhD, 2 and Kui Hong, MD, PhD. Adherence with cardiovascular medications and the outcomes in patients with coronary arterial disease: “Real‐world” evidence. Clinical Cardiology. September 18, 2022. 5. Smilowitz et al. Risks of Non-Cardiac Surgery Early after Percutaneous Coronary Intervention. Am Heart J. 2019 November; 217: 64–71.

A new tool could one day help clinicians better predict resistance to immunoglobulin therapy among children with Kawasaki disease in the United States. Compared to the Kobayashi score -- the most widely used method in Japan for predicting resistance to the antibody, intravenous immunoglobulin (IVIG), in Kawasaki disease -- the newly developed tool is twice as accurate for Western New York children, achieving a sensitivity (detection) rate of 54%. A new tool under development by University at Buffalo researchers could one day help clinicians better predict resistance to immunoglobulin therapy among children with Kawasaki disease in the United States. The new tool -- described in a study published earlier this year in the Journal of Pediatric Pharmacology and Therapeutics - lays the groundwork for North America's first test to predict resistance to therapeutic treatments for the rare disease, but severe inflammatory disease. Compared to the Kobayashi score -- the most widely used method in Japan for predicting resistance to the antibody, intravenous immunoglobulin (IVIG), in Kawasaki disease -- the UB-developed tool is twice as accurate for Western New York children, achieving a sensitivity (detection) rate of 54%. "Neither system is highly sensitive, but the new score may more accurately identify IVIG resistance in Western New York children and other North American populations than the Kobayashi score," says first author and UB alum Jasdip Singh, PharmD, global scientific communications manager at Eli Lilly and Company. Kawasaki disease is an acute inflammation of the blood vessels that primarily affects children younger than 5 years of age. The illness is the leading cause of acquired heart disease among children in the U.S., according to the Centers for Disease Control and Prevention. If left untreated, children with the disease can experience life-threatening coronary artery aneurysms. The standard treatment for Kawasaki disease is IVIG and aspirin. Although most cases are resolved after a single dose of IVIG, 10-20% of children are IVIG resistant and have a higher chance of developing coronary artery aneurysms. Kawasaki disease occurs worldwide, with the highest incidence in Japan. The Kobayashi score can predict IVIG resistance with a sensitivity rate of 86%, however, the system has limited use outside of Japan -- likely due to the nation's homogenous population, say the researchers. The Kobayashi score has a low sensitivity rate of 33% among the varied ethnicities of North America children. The UB study analyzed 208 cases of children hospitalized with Kawasaki disease at a Buffalo hospital between 2000-15. The data were divided into two groups: IVIG susceptible or resistant. Four variables that differed between the groups were identified and used to create a new prediction score. The variables included: white blood cell count, neutrophil percentage, age, and serum albumin concentration. Each variable is assigned one point and a score of three or greater denotes high risk for IVIG resistance. To ensure the new scoring system is applicable across geographical locations, the accuracy of the tool was tested on Kawasaki disease patient data obtained from Western New York, Boston and China. The new tool had a sensitivity rate of 54% for the Western New York data set, while the rate for the Kobayashi score was 26%. For the Boston data set, the new score had a sensitivity of 40%; far higher than the 0% rate for the Kobayashi score. The sensitivity rate for the new score was the lowest among the China data set, at 27%, whereas the Kobayashi score had a sensitivity rate of 36%. "Our study, although small, highlights the challenges with predicting IVIG resistance. These findings underscore the regional variations that exist with Kawasaki disease and the limitations with applying a risk prediction tool to a population outside of the one it was derived from," says corresponding author, Nicholas Fusco, PharmD, clinical associate professor of pharmacy practice in the UB School of Pharmacy and Pharmaceutical Sciences. "The new score resulted in improved sensitivity, but many children with true resistance may be missed," he says. The researchers say that future studies are needed to determine if the new score is applicable in additional U.S. regions outside of the Western New York area; as well as to identify additional variables to improve the accuracy of the tool. An interdisciplinary collaboration between the fields of pharmacy and medicine, additional investigators on the study include Mark Hicar MD, PhD, associate professor of pediatrics in the Jacobs School of Medicine and Biomedical Sciences at UB; and Arthur Chang, MD, UB alum and assistant professor of pediatrics at the University of Nebraska Medical Center.

GENEVA, Switzerland, Sept. 9, 2022 /PRNewswire/ -- An 82-year-old Taiwanese man has become the first patient to be enrolled in the initial Erectile Dysfunction (ED) randomized clinical trial (RCT) involving SELUTION SLR™, MedAlliance's novel sirolimus-eluting balloon. Continue Reading First patient enrolled in Erectile Dysfunction prospective randomized study with SELUTION SLR The PERFECT-SELUTION FIM ( PElvic Revascularization For Ere CTile dysfuction-SELUTION First-In-Man) study involves a total of 54 patients suffering from distal internal pudendal-penile artery stenotic disease and ED. They are being randomized to treatment with either SELUTION SLR or plain old balloon angioplasty (POBA), then followed-up for a period of 12 weeks. The primary efficacy endpoint of the study is angiographic binary restenosis (>50% lumen diameter stenosis) defined by computer tomography (CT) and the primary safety endpoint is the rate of major adverse events. "We are excited to begin this study on such a long-suffering patient population. We hope that this study will give these patients a better chance of a normal life, and look forward to the results," said Tzung-Dau Wang, Professor of Medicine and Director of Cardiac Cath Lab, National Taiwan University Hospital, who has performed pudendal and penile artery angioplasty with conventional devices ( POBA and/or stents) on more than 500 patients with arteriogenic erectile dysfunction and acknowledged that restenosis occurred in more than 30% of treated patients. "We do need a state-of-the-art technology to break this barrier. We are pleased to initiate this study: the first patient has responded well to this therapy." "We have been very pleased with the clinical results of this technology in many applications: in-stent restenosis, coronary de novo, both below and above the knee, AV fistula and now erectile dysfunction. This combination drug-device technology seems to be very versatile, and we look forward to the results from this physician-initiated study, as this is clearly an unmet need touching the lives of hundreds of millions people," added Jeffrey B. Jump, Chairman and CEO of MedAlliance. This study follows a successful feasibility study conducted in Europe in August 2021, involving ten patients with ED. It is estimated that over 300 million men worldwide were affected by ED in 2020, a figure projected to increase to 322 million by 2025. Nearly 30% of these were aged between 40 and 70. The most common cause of ED is vascular disease. 70% of physical-related causes of ED are due to reduced blood circulation to the penis. PDE5 inhibitors (e.g. Viagra, Cialis) are the most commonly used form of drug treatment for ED, but up to 50% of those patients treated, experience a suboptimal response. A potential alternative therapy for these patients is to treat the pudendal and/or penile arteries via the percutaneous approach, using a coronary metallic stent or a balloon. Atherosclerotic occlusive disease of the ilio-pudendal-penile arteries resulting in arterial insufficiency to the penis has been reported to affect up to 75% of patients with ED. SELUTION SLR was awarded CE Mark Approval for the treatment of peripheral artery disease in February 2020 and for the treatment of coronary arterial disease in May 2020. The US FDA has awarded SELUTION SLR with four breakthrough designations: for the treatment of atherosclerotic lesions in native coronary arteries; coronary in-stent restenosis; peripheral below-the-knee and AV-Fistula indications. In August 2021, the first of over 3,000 patients was enrolled in a ground-breaking coronary randomized controlled study comparing SELUTION SLR with a limus drug-eluting stent [DES]. This is the largest DEB study ever initiated and has the potential to change medical practice. MedAlliance's DEB technology involves unique MicroReservoirs made from biodegradable polymer intermixed with the anti-restenotic drug sirolimus. These MicroReservoirs provide controlled and sustained release of the drug for up to 90 days1. Extended release of sirolimus from stents has been proven highly efficacious in both coronary and peripheral vasculatures. MedAlliance's proprietary CAT™ (Cell Adherent Technology) enables the MicroReservoirs to be coated onto balloons and adhere to the vessel lumen when delivered via an angioplasty balloon. Media Contact: Richard Kenyon [email protected]com +44 7831 569940 About MedAlliance MedAlliance is a privately-owned medical technology company. It is headquartered in Nyon, Switzerland, with offices in Germany, Singapore, UK and USA. MedAlliance specializes in the development of ground-breaking technology and commercialization of advanced drug device combination products for the treatment of coronary and peripheral artery disease. For further information visit: 1. Drug concentration evident in MicroReservoirs and tissue – Data on file at M.A. Med Alliance SA Photo: Logo: SOURCE MedAlliance