Cardioxyl Pharmaceuticals Initiates Dose-Defining Phase IIA Study of Its Lead Candidate, CXL-1020, In Heart Failure Patients
Following Positive Results in Phase I/IIa Dose-Escalation Trial, Cardioxyl Continues to Evaluate Clinical Safety and Tolerability of CXL-1020
Chapel Hill, NC – August 26, 2010 – Cardioxyl Pharmaceuticals, Inc., a clinical-stage pharmaceutical company developing therapeutic agents for the treatment of cardiovascular disease, today announced that it has initiated a dose-defining Phase IIa trial of its lead drug candidate, CXL-1020, for the treatment of patients with acute decompensated heart failure (ADHF). ADHF is the leading diagnosis for patients at the time of discharge from U.S. hospitals and the most common cause of hospitalization for patients over 65 years of age. i
"Following the significant clinical results from our recently completed Phase I/IIa dose escalation study demonstrating CXL-1020's attractive hemodynamic and safety profile, we are excited to continue to evaluate this important new therapy for patients with ADHF," said Chris Kroeger, M.D., Cardioxyl Pharmaceuticals President and Chief Executive Officer. "We believe that CXL-1020 is the only cardiovascular product in development that provides the ideal balance of blood vessel dilation combined with direct enhancement of cardiac diastolic and systolic function."
Cardioxyl's placebo-controlled, multi-center Phase IIa study is designed to further define a suitable clinical dosage for CXL-1020, and is being conducted at up to 20 U.S. and international clinical sites. This three-cohort study will enroll 54 to 66 cardiac patients with decompensated heart failure. Hemodynamic parameters are being evaluated during intravenous infusion of CXL-1020 at several dose levels. Investigators will assess hemodynamics utilizing invasive and non-invasive techniques including both echocardiography and direct Swan-Ganz catheter-based measures of heart pressures and function. The primary efficacy endpoints for this study include an evaluation of dose-related hemodynamic effects. The study will also expand the database of safety information for CXL-1020. Further information on this trial can be found at www.clinicaltrials.gov at reference number NCT01096043.
Juan Aranda, M.D., Professor of Medicine, Director of Cardiac Transplantation at The University of Florida, Gainesville, who is an investigator in the Phase IIa study commented, "Based on Phase I/IIa clinical results with CXL-1020, we have reason to believe this cardiovascular drug will be an important new option in the treatment of patients with ADHF. This Phase IIa study will provide additional valuable insight into the potential benefits of CXL-1020 for these seriously ill patients."
Cardioxyl has developed a nitroxyl chemistry platform technology that serves as the foundation for the company's drug discovery efforts. In research published by Cardioxyl's scientific founders from Johns Hopkins University, nitroxyl was shown to have positive vasodilatory and direct myocardial effects. CXL-1020, a proprietary nitroxyl donor, is Cardioxyl's lead compound for the intravenous treatment of acute decompensated heart failure (ADHF). In pre-clinical models of heart failure, CXL-1020 improves cardiovascular performance by enhancing the contractility (inotropy) and relaxation (lusitropy) of the failing heart and dilating the peripheral vasculature (vasodilation), without increasing heart rate or myocardial oxygen consumption. Cardioxyl completed a Phase I/IIa safety and dose-escalation study of CXL-1020 in stable chronic heart failure subjects and has announced initiation of a Phase IIa trial. Based on all pre-clinical studies to date, CXL-1020 is anticipated to improve the symptoms, hemodynamics and clinical status of patients with ADHF.
About Acute Decompensated Heart Failure (ADHF) & Current Treatment Options
ADHF is the leading diagnosis at the time of discharge from U.S. hospitals and the most common cause of hospitalization for patients over 65 years of age.i Well over $39 billion was spent in the U.S. in 2009 for the medical care of heart failure patients. ADHF is a deadly condition, with in-hospital mortality rates of two to six percent and six-month readmission rates as high as 30 to 60 percent. Episodes of ADHF are marked by a severe reduction of cardiac function that typically results in fluid accumulation in the lungs (pulmonary edema) and consequent severe shortness of breath. There were 1.1 million hospitalizations for acute heart failure in the U.S. in 2006. Among patients hospitalized with ADHF, the 30-day mortality rate is approximately 11 percent and the one-year mortality rate is 34 percent. These poor outcomes indicate the clear need for better therapies to treat this patient population.
Despite the severity of the condition, the treatment options available for patients with ADHF remain limited. Current first-line treatments target the removal of excess fluid (diuresis) and preload and afterload reduction (vasodilation). In order to improve the hemodynamic profile of the heart and increase cardiac contractility, a physician may also administer an intravenous inotropic agent such as dobutamine (beta-adrenergic agonist) or milrinone (PDE3-inhibitor). Administration of dobutamine or milrinone often requires very close monitoring in the hospital's cardiac or intensive care unit setting due to the life-threatening safety risks associated with these drugs, including ventricular/atrial arrhythmias, hypotension, sudden cardiac death, and other potential adverse long term outcomes.ii,iii
About Cardioxyl Pharmaceuticals
Cardioxyl Pharmaceuticals is a clinical-stage pharmaceutical company focused on the discovery and development of new classes of safe and effective therapeutic agents for the treatment of cardiovascular disease. Cardioxyl has developed industry-leading expertise in the chemistry, biology and clinical applications of HNO (nitroxyl) technology. The company's core HNO platform has generated several preclinical and clinical candidates, including the company's lead compound, CXL-1020, currently in clinical development for ADHF. Cardioxyl is a privately held company financed by life science venture investors Aurora Funds and New Enterprise Associates.
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iHeart Disease and Stroke Statistics 2009 Update. A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009; 119:e1-e161
iiGheorghiade, M. Reassessing treatment of acute heart failure syndromes: the ADHERE Registry. Eur Heart J Suppl. 2005 7: B13-B19
iiiJong, P et al. Prognosis and Determinants of Survival in Patients Newly Hospitalized for Heart Failure. Arch Int Med, 2002; 162:1689-1694