Alteon Inc announced initial results from its multi-center Phase 2b SAPPHIRE and SILVER clinical trials of the company's lead A.G.E. Crosslink Breaker, ALT-711, in the treatment of patients with uncontrolled systolic hypertension. The five-arm SAPPHIRE trial and the two-arm SILVER trial evaluated ALT-711's effectiveness in a total of 768 patients having elevated systolic blood pressure (systolic hypertension) without or with enlargement of the left ventricle of the heart. The trials were dose-ranging, double-blind, placebo-controlled and conducted at over 60 sites nationwide. All patients were maintained on background hypertension medication.

ALT-711 did not demonstrate statistical significance as compared to placebo against the pre-specified primary endpoint of reduction of systolic blood pressure by office cuff pressure measurement at the highest of the four active dose levels, 210 mg per day. The data analysis was confounded by a 6-10 mm Hg drop in systolic blood pressures in all arms of the SAPPHIRE and SILVER trials, including placebo, during the first two weeks after patient randomization. However, patients in the SAPPHIRE "intent-to-treat" population demonstrated efficacy net of placebo, in the 2-3 mm Hg range by cuff pressure, at the lower end of the ALT-711 dosing range. In patients who completed their dosing regimen in the SAPPHIRE study, this effect at lower doses was amplified and strengthened to about 4 mm Hg net of placebo by ambulatory blood pressure measurements (ABPM). ALT-711 was safe and well tolerated across all dosing groups. No differences were noted between the SAPPHIRE and SILVER results.

"We believe that this is a meaningful signal of ALT-711's activity," said George L. Bakris, Professor of Preventive Medicine and Internal Medicine and Director of the Hypertension Clinical Research Center at Rush-Presbyterian St. Luke's Medical Center in Chicago and lead investigator on the SAPPHIRE and SILVER trials. "A 4 mm Hg reduction in systolic blood pressure on top of existing hypertension medications, if confirmed in further studies, would be an important addition to the treatment of this patient population."

"Based on discussions with our external advisors, we believe that the current results are robust and consistent with earlier findings about the biological activity of ALT-711," said Robert C. deGroof, Senior Vice President, Scientific Affairs. "We now have further evidence of efficacy against systolic hypertension in addition to existing evidence in diastolic heart failure (DHF), medical conditions that are due to age-related stiffening and for which there are clear, unmet needs."

"Following on what has been reported in previous preclinical and clinical evaluation, the SAPPHIRE and SILVER data support continued development of ALT- 711 in systolic hypertension to confirm the appropriate dose," said Kenneth I. Moch, President and CEO of Alteon. "This new information leads us to plan a simple and relatively short confirmatory dose-ranging and mechanism of action study, and we are already working with our advisors to refine our follow-on clinical strategy. Assuming positive data from the next Phase 2 trial, we anticipate that we would enter into Phase 3 pivotal trials in systolic hypertension in 2005."

Earlier this year, Alteon announced that treatment with ALT-711 in DHF (the DIAMOND study) demonstrated that patients who received 210 mg of ALT-711 twice a day in an open-label, 16-week trial experienced a statistically significant reduction in left ventricular mass, a marked improvement in left ventricular diastolic filling and a positive effect on patients' quality of life.