International Society for Heart & Lung Transplantation and XDx Announce Results of IMAGE Study Demonstrating Non-Inferiority of AlloMap(R) to Routine Biopsy for Routine Surveillance After Heart Transplantation

CHICAGO, April 22 /PRNewswire/ -- The International Society for Heart & Lung Transplantation (ISHLT) and XDx, Inc., a molecular diagnostics company focused on noninvasive gene expression tests for the monitoring of immune-mediated conditions, today announced results from the Invasive Monitoring Attenuation through Gene Expression (IMAGE) clinical trial.

The IMAGE results were presented during a plenary session at the ISHLT 30th Anniversary Meeting & Scientific Sessions in Chicago and coincide with publication in the New England Journal of Medicine. The Journal is publishing the study today online as an "early release" to coincide with the data presentation at the ISHLT meeting and will follow with publication in the June 17, 2010, print edition.

The 602-patient IMAGE trial demonstrated that XDx's AlloMap® Molecular Expression Testing, a noninvasive gene expression test used to aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection at the time of testing in conjunction with standard clinical assessment, was non-inferior to conventional endomyocardial biopsy for monitoring post-transplant patients with respect to clinical outcomes. The study also showed the use of AlloMap as part of overall patient management resulted in significantly fewer biopsies compared to the current standard of routine biopsies.

"The IMAGE trial is the first study in the field of cardiac transplantation that evaluates patient outcomes associated with the use of a biomarker for clinical decision making," said Michael Pham, M.D., M.P.H., the study's co-lead investigator and a transplant cardiologist at the Stanford University Medical Center and Veterans Affairs Palo Alto Health Care System. "In this large randomized trial involving over 600 heart transplant recipients who were at least six months post-transplantation at the time of their participation, we found that patients undergoing rejection monitoring using a gene-expression profiling test of peripheral blood specimens underwent significantly fewer biopsies and were more satisfied with the biopsy-minimization approach compared to patients who underwent routine biopsies at regular intervals. Patients in both groups experienced similar rates of clinically apparent rejection, cardiac dysfunction, death or the need for a second transplant."

Each year in the United States, about 2,200 individuals receive heart transplants. Advances in immunosuppression have improved one-year survival rates to nearly 90 percent following cardiac transplantation, but the risk of acute cellular rejection persists for several years post-transplantation and is associated with graft loss. Heart transplant recipients typically undergo 12 biopsies in the first year following transplantation and four biopsies in the second year.  Many centers continue surveillance biopsies for several more years.  Invasive biopsy procedures may be associated with discomfort, inconvenience and infrequent but potentially serious risks of complications.

AlloMap was cleared by the U.S. Food and Drug Administration (FDA) in 2008 to aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection at the time of testing in conjunction with standard clinical assessment. XDx has submitted the results of the IMAGE trial to the FDA for a label extension for AlloMap compared with biopsy.

IMAGE Trial Design and Results

The IMAGE study was a multicenter clinical trial of stable heart transplant patients conducted at 12 heart transplant centers in the United States. Patients were randomized either to receive the AlloMap test or the conventional endomyocardial biopsy method of surveillance monitoring. The patients enrolled into the study when they were six months to five years post-transplant and then followed by the assigned surveillance method for up to two years. The primary endpoint was an event of rejection with hemodynamic compromise, graft dysfunction due to other causes, death or retransplantation. Secondary outcomes included the number of biopsies performed. Patient satisfaction and quality of life were also assessed.

Results showed that, during a median follow up of 19 months, cardiac transplant recipients monitored with AlloMap had similar two-year cumulative rates of rejection with hemodynamic compromise, graft dysfunction from other causes, death or retransplantation as recipients who were monitored with routine biopsies (14.5 percent vs. 15.3 percent). The two-year rates of death or retransplantation were also similar in the AlloMap and biopsy arms (6.3 percent and 5.5 percent). The trial also showed that patients randomized to AlloMap underwent significantly fewer biopsies per person year of follow-up compared with patients in the biopsy group (0.5 biopsies/year vs. 3.0 biopsies/year). Patient satisfaction with AlloMap was higher compared with the biopsy method.

About AlloMap® Molecular Expression Technology

AlloMap Molecular Expression Testing is a gene expression test that uses a simple, noninvasive method of blood sample collection and can be used to reliably indicate the low probability of acute cellular rejection in stable heart transplant recipients. AlloMap testing measures the expression levels of 20 specific genes in the blood. The combined expression of these genes, represented as an AlloMap test score, can help a physician evaluate whether a patient is at low risk for rejection when used together with standard clinical assessment. AlloMap, performed in the XDx CLIA certified laboratory, has been commercially available since 2005 and was cleared by the U.S. Food and Drug Administration in 2008.

About XDx

XDx, based in Brisbane, Calif., is a molecular diagnostics company focused on the discovery, development and commercialization of noninvasive gene expression-based tests for the monitoring of transplant rejection and autoimmune diseases. The company has developed AlloMap® Molecular Expression Testing, an FDA-cleared test, which provides transplant physicians with a tool to aid in the determination of the probability of acute cellular rejection for post-cardiac transplant patient management. Some of the AlloMap technology developed and implemented by XDx in heart transplant patient management may be applicable to other conditions that involve transplant rejection and diseases that affect the immune system. XDx's noninvasive technology offers the potential to decrease healthcare costs and significantly improve the quality of life for patients with a variety of life-threatening or life-altering immune-mediated diseases. For more information, please visit www.xdx.com.

About ISHLT

The International Society for Heart and Lung Transplantation (ISHLT) is a not-for-profit organization dedicated to the advancement of the science and treatment of end-stage heart and lung diseases.  Created in 1981, the Society now includes more than 2,200 members from 45-plus countries, representing a variety of disciplines involved in the management and treatment of end-stage heart and lung disease.  

ISHLT maintains two vital databases. The International Heart and Lung Transplant Registry is a one-of-a-kind registry that has been collecting data since 1983 from 223 hospitals from 18 countries. The ISHLT Mechanical Circulatory Support Device (MCSD) database has been collecting data since 2002 with the aim of identifying patient populations who may benefit from MCSD implantation; generating predictive models for outcomes; and assessing the mechanical and biological reliability of current and future devices.  In Fall 2006, ISHLT released the first international guidelines for heart failure patient management and in 2010, the organization will release the first international guidelines for heart transplant patients.  For more information, visit www.ishlt.org.

SOURCE International Society for Heart & Lung Transplantation and XDx