Dec 11, 2018

CardioCell and MedStar Heart & Vascular Institute Initiate Phase IIa Clinical Trial to Assess Stem Cell Therapy Effects in Heart Failure Patients With Left Ventricular Assist Devices (LVADs)

FDA approves first study involving multiple intravenous injections of mesenchymal stem cells for cardiovascular indications SAN DIEGO—Dec. 11, 2018—CardioCell, a biotechnology company that uses allogeneic stem cells for cardiovascular indications, has partnered with MedStar Heart & Vascular Institute in Washington, D.C., to begin a Phase IIa study using its patented low-oxygen grown mesenchymal stem cells (itMSCs). The trial aims to determine whether the itMSCs improve myocardial function in patients with severe heart failure—severe enough to require the implantation of a left ventricular assist device (LVAD). This new study advances research based on preclinical studies demonstrating that—in mice with acute myocardial infarction and in mice with ischemic cardiomyopathy—the intravenous infusion of MSCs diminished the excessive inflammatory responses present in these conditions and, most importantly, markedly improved left ventricular function. Safety and promising signals of efficacy was also demonstrated in a trial in patients with stable chronic heart failure “Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial.”  These data were published in Circulation Research in January 2017. Based on data from these and other studies, the FDA approved this new trial, which for the first time includes the intravenous administration of MSCs, and their administration at three separate times. “The focus of this trial is on safety and feasibility. If successful, pivotal trials will follow to establish whether repeated infusions of itMSCs are effective strategies for treating LVAD patients, resulting in improved symptoms and outcomes,” says Ron Waksman, M.D., director, Cardiovascular Research and Advanced Education, MedStar Heart & Vascular Institute. Addressing Inflammation in Heart Failure Patients With LVADs Innovative therapies to help patients with LVAD support—more than 200,000 Americans—are in high demand since those patients have a high incidence of serious complications. Persistent inflammation is a probable major cause of clinical and cardiac deterioration in LVAD patients. “We have developed compelling evidence—using mouse models of heart attack and of heart failure—that one of the major mechanisms leading to progressive myocardial dysfunction in heart failure patients is the presence of persistent and inappropriate inflammation,” says Stephen Epstein, M.D., director of Translational and Vascular Biology Research at MedStar Heart & Vascular Institute. “We demonstrated that itMSCs have marked anti-inflammatory effects when injected intravenously to the mice, and that these anti-inflammatory effects led to markedly improved heart function. If we are successful in showing intravenously delivered itMSCs improve outcomes in LVAD patients, the results would likely extend to the general population of heart failure patients, and, in the process, fundamentally transform current paradigms for treating heart failure.” Uniquely Manufactured Stem Cells With A Novel Delivery Strategy Unlike MSCs from other sources that are grown under normoxic conditions, CardioCell’s bone-marrow-derived, allogeneic MSCs are grown under hypoxic conditions. In vivo experiments demonstrate cells that are exposed to hypoxic conditions show greater homing and engraftment than cells grown under normoxic conditions. Compared to MSCs manufactured under normal oxygen conditions, our hypoxia grown MSCs secrete higher levels of growth factors and other important proteins associated with neoangiogenesis, healing, and powerful anti-inflammatory effects. The latter has been demonstrated in the pre-clinical and clinical studies cited in Circulation Research. Virtually all previous attempts to use stem cells to treat cardiac disease relied on the concept that the cells had to be delivered directly to the target tissue—the heart—and this, in turn, required catheter-based, invasive delivery strategies.In addition to being impractical, the MedStar Heart & Vascular Institute investigators suspected that repeated stem cell injections—every few months—would be required for adequate and sustained treatment effect. “Cardiologists currently have few options for treating cardiac deterioration in heart failure patients with LVADs,” said Dr. Sergey Sikora, CardioCell’s president and CEO. “CardioCell is pleased to partner with the renowned cardiology team at MedStar Heart & Vascular Institute to identify innovative approaches to improve patient outcomes. In this case, we are capitalizing on the unique properties of our hypoxically grown stem cells. Preclinical studies demonstrated that our itMSCs are effective in improving myocardial function when given intravenously—the only practical and safe route of delivery that can be used when multiple injections over time are necessary.” About the Trial This is a Phase IIa, double blind, placebo-controlled, randomized study in subjects with advanced ischemic heart failure who are supported by LVADs. The study will enroll 30 subjects at MedStar Heart & Vascular Institute and will consist of two cohorts. Enrolled subjects will be stratified by LVAD device type (HeartWare HVAD, HeartMate II or HeartMate III) and randomized at 1:1 into an experimental group (n=15) or a placebo group (n=15), respectively. Subjects in the experimental group will receive 1.5 million cells per kg, and subjects in the placebo group will receive 1 mL/kg Lactated Ringer’s Solution at baseline, one month and two months. All study participants will receive the MSCs or placebo within seven days of the specified timing. Physical examination and concomitant medications will be recorded at each infusion visit, as well as 90 and 180 days later. Complete examinations will be used to assess disability and functional status at baseline and at the visits scheduled at one, two, and three months after the initial administration. A baseline 2D and 3D and Doppler transthoracic echocardiography with speckle-tracking and gated blood pool SPECT ventriculography for assessment of right and left ventricular systolic function and volumes will be performed at baseline and at specific time points during follow-up. All echocardiograms will be assessed in a blinded core lab. All SPECT ventriculograms will be assessed by a blinded observer. Subjects will continue all of their regular medications unless contraindicated. The principal investigator for the study is Selma Mohammed, M.D., Ph.D., director of Heart Failure & Transplant Services at MedStar Heart & Vascular Institute. About CardioCell Founded in San Diego, California, in 2013, CardioCell is a global biotechnology company that explores therapeutic applications of unique patented ischemia-tolerant mesenchymal stem cells (itMSCs) manufactured under cGMP conditions. CardioCell has exclusive worldwide rights for the manufacturing, exploration and commercialization of itMSCs for therapeutic cardiovascular indications. For more information, visit www.stemcardiocell.com. About MedStar Heart &Vascular Institute MedStar Heart & Vascular Institute is a national leader in the research, diagnosis and treatment of cardiovascular disease. A network of 10 hospitals and 150 cardiovascular physicians throughout Maryland, Northern Virginia and the Greater Washington, D.C., region, MedStar Heart also offers a clinical and research alliance with Cleveland Clinic Heart & Vascular Institute, the nation’s #1 heart program. Together, they have forged a relationship of shared expertise to enhance quality, improve safety and increase access to advanced services. MedStar Heart & Vascular Institute was founded at MedStar Washington Hospital Center, home to the Nancy and Harold Zirkin Heart & Vascular Hospital. Opened in July 2016, the hospital ushered in a new era of coordinated, centralized specialty care for patients with even the most complex heart and vascular diagnoses.