Alagebrium Demonstrates Important Cardiac Benefits in Diastolic Dysfunction and Endothelial Function Studies

- PEDESTAL and Endothelial Function Data Presented at the American Heart Association Scientific Sessions 2005 - 


PARSIPPANY, N.J., Nov. 15  /PRNewswire-FirstCall/ -- Alteon Inc. (AMEX:ALT) announced today that data demonstrating the ability of its lead A.G.E. Crosslink Breaker alagebrium to improve overall cardiac function are being presented today at the American Heart Association Scientific Sessions in Dallas, TX, by two independent research teams.  Data presented from the Phase 2a PEDESTAL trial in diastolic dysfunction demonstrated the ability of alagebrium to improve measures of diastolic function, including a significant reduction in left ventricular mass.  A second Phase 2a study found the compound to significantly improve endothelial function.  Both studies point to the importance of the continued development of alagebrium and A.G.E. Crosslink Breakers as a novel class of compounds that may help reduce cardiovascular risk.

The poster presentation "Improvements in Diastolic Function Among Patients with Advanced Systolic Heart Failure Utilizing Alagebrium, an Oral Advanced Glycation End-product Crosslink Breaker" describes the key findings from Alteon's diastolic dysfunction trial, known as PEDESTAL (Patients with Impaired Ejection Fraction and Diastolic Dysfunction: Efficacy and Safety Trial of Alagebrium).  Twenty-two patients were treated in an open-label two dose (35 mg and 210 mg bid) regiment and followed by echocardiography.  The data revealed absolute improvements from a combined analysis of both dose groups in Doppler measures of diastolic function, including the early/late (E/A) atrial filling phase ratio (3.3+/-1.4vs. 2.6+/-1.4) (p=0.18), deceleration time (DT) (148+/-33 vs. 188+/-60), (p=0.04), isovolumetric relaxation time (IVRT) (88+/-11.9 vs. 113.1+/-31) (p=0.04) and concomitant reduction of left atrial pressure (25.0+/-8 vs. 19+/-8) (p=0.11).  In addition, regression of left ventricular mass (g) (297+/-57 vs. 246.+/-51) (p=0.002) and left ventricular end-diastolic volume (ml) (297+/-57 vs. 246+/- 51) was achieved.

Author Vinay Thohan, M.D., Assistant Professor of Medicine, Methodist DeBakey Heart Center, Houston, TX, concluded, "Alagebrium had important benefits among patients with systolic heart failure and diastolic dysfunction. These benefits included improved measures of diastolic function, hemodynamics and cardiac remodeling.  Future investigations aimed at evaluating the expected clinical improvements are warranted."

In the study, "Improved Flow-Mediated Arterial Vasodilation by Advanced Glycation Crosslink Breaker, Alagebrium Chloride (ALT-711), in Older Adults with Isolated Systolic Hypertension," conducted at Johns Hopkins University School of Medicine under grants from the National Heart, Lung and Blood Institute and the Society of Geriatric Cardiology, 13 adults with isolated systolic hypertension on stable antihypertensive therapy received a 2-week placebo run-in followed by 8 weeks of oral alagebrium (210 mg bid).  Data measurements were taken after placebo run-in and after 8 weeks of therapy. Treatment with alagebrium reduced carotid augmentation index (AI), a measure of arterial stiffness, by 37% (0.3+/-0.04 to 0.2+/-0.05, p=0.007) and carotid augmented pressure from 16.4+/-10 to 9.6+/-9 mmHg (p