MONTVALE, N.J., May 13 /PRNewswire-FirstCall/ -- Synvista Therapeutics, Inc. has dosed the first patient in a 160-patient Phase 2 study of alagebrium in patients with diastolic heart failure. BREAK (Beginning a Randomized Evaluation of the A.G.E. [Advanced Glycation End Product] Breaker Alagebrium in Diastolic Heart Failure) is a randomized, double-blind, placebo controlled study to assess the effect of six months of oral treatment with 400mg (200mg twice daily) alagebrium versus placebo in patients diagnosed with diastolic heart failure as verified by echocardiography. The trial will ultimately enroll 80 patients per cohort and be conducted in as many as 25 centers in the United States. Investigators intend that at least half of the study subjects will have diabetes mellitus. The primary efficacy measure of the study is improvement of exercise tolerance as assessed by the six-minute walk test, an accepted regulatory endpoint. In addition, there will be a number of secondary and tertiary measurements including the effect on carboxymethyllysine (CML), a biomarker of A.G.E., against which Synvista has developed a proprietary monoclonal antibody, 4G9, which can be developed into an in-vitro diagnostic test.
"This is a very important study for alagebrium. By looking at the results of the BREAK study along with our BENEFICIAL study in systolic heart failure, we will have a better understanding of the role of A.G.E.s in heart failure," said Noah Berkowitz, M.D., Ph.D., President and Chief Executive Officer of Synvista Therapeutics, developer of alagebrium. "Based on what we learn from these studies, there is immense potential to expand the scope of treatment modalities for heart failure. We look forward to seeing the results of the BREAK study before the end of next year."
About Alagebrium
Alagebrium is Synvista's clinical candidate for interfering with A.G.E.- related sclerosis and fibrosis of the heart, kidney and other tissues leading to heart failure, diabetic nephropathy and other disorders. It is a proprietary A.G.E. crosslink breaker that functions unlike any previously developed pharmaceutical agents to reverse the disease states associated with age or diabetes-related stiffening of vessels, tissues and organs. Alagebrium has completed a series of single- and multiple-dose Phase 1 studies in humans and has demonstrated efficacy in heart failure in several open-label Phase 2 trials. To date approximately 1,000 patients have received alagebrium treatment and the drug continues to exhibit a clean safety profile.
About Heart Failure
Heart failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. The primary manifestations of heart failure are dyspnea and fatigue, which may limit exercise tolerance, result in fluid retention, and lead to pulmonary congestion and peripheral edema. These abnormalities impair the functional capacity and quality of life of affected individuals.
Heart failure is a major and growing global public health problem. Approximately 5 million patients in the U.S. and about 10 million in Europe have heart failure, according to the American Heart Association. The number of heart failure deaths has increased steadily despite advances in treatment. Heart failure results in more than 1 million hospitalizations at a cost of more than $15 billion annually in the U.S. alone.
Most of the available treatments for heart failure are not aimed at the underlying pathophysiological processes that occur in the heart and blood vessels. In this respect, the Company believes that accumulation of A.G.E.s might prove to be a promising, novel target for the treatment of heart failure. A.G.E.s are proteins formed by oxidative or non-oxidative reactions. A.G.E.s cause the formation of collagen cross-links, which result in increased myocardial stiffness whereby the stiff ventricle fails to relax adequately between beats and allow blood to fill the chamber. As a result, blood backs up into the lungs and makes patients short of breath. More than 50% of patients with symptoms of heart failure have evidence of a stiff non-compliant ventricle (heart chamber) by echocardiogram.
About Synvista Therapeutics
Synvista Therapeutics is a biopharmaceutical company developing drugs to treat and prevent cardiovascular disease and nephropathy in people with diabetes. The Company believes it has identified several product candidates that represent novel approaches to some of the largest pharmaceutical markets. The Company's portfolio includes orally bioavailable, organoselenium mimics of glutathione peroxidase. These compounds metabolize lipid peroxides and have the potential to limit myocardial damage subsequent to a myocardial infarction. The Company is developing a clinical diagnostic test, based on cardiovascular risk assessment, using Haptoglobin characterization, to identify patients at high risk for cardiovascular complications of diabetes.
Synvista Therapeutics also is developing alagebrium, a proposed breaker of AGEs for the treatment of diastolic heart failure. This disease represents a rapidly growing market of unmet medical need, particularly common among diabetic patients. Alagebrium has demonstrated relevant clinical activity in two Phase 2 clinical trials in heart failure, as well as in animal models of heart failure and nephropathy, among others. Alagebrium has been tested in approximately 1,000 patients in multiple Phase 1 and Phase 2 clinical trials, allowing Synvista Therapeutics to assemble a sizeable human safety database. For more information, please visit the Company's website at www.synvista.com.
Any statements contained in this press release that relate to future plans, events or performance are forward-looking statements that involve risks and uncertainties including, but not limited to, the risks associated with the events described in this press release, future clinical development of Synvista Therapeutics' product candidates, and other risks identified in Synvista Therapeutics' filings with the Securities and Exchange Commission. Further information on risks faced by Synvista are detailed under the caption "Risk Factors" in Synvista Therapeutics' Annual Report on Form 10-K for the year ended December 31, 2007. These filings are available on a website maintained by the Securities and Exchange Commission at http://www.sec.gov. The information contained in this press release is accurate as of the date indicated. Actual results, events or performance may differ materially. Synvista Therapeutics undertakes no obligation to publicly release the result of any revision to these forward- looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.
CONTACT: Synvista Therapeutics, Inc., +1-201-934-5000, ir@synvista.com; or
Investor-Media Relations Contacts, Kim Sutton Golodetz, kgolodetz@lhai.com,
or Jules Abraham (media), jabraham@lhai.com, both of Lippert-Heilshorn &
Associates, +1-212-838-3777
Web site: http://www.synvista.com/
