Alteon's ALT-711 Shows Highly Significant Reduction in Systolic Blood Pressure In Detailed Analysis of Sapphire/Silver Clinical Trial
Monday February 23, 9:10 am ET
- Data to be Presented at Upcoming Scientific Forum, May 2004 -
PARSIPPANY, N.J., Feb. 23 /PRNewswire-FirstCall/ -- Alteon Inc. (Amex: ALT - News) today announced important findings from a post hoc analysis of ambulatory blood pressure measurements (ABPM) in the Phase 2b SAPPHIRE/SILVER trial of Alteon's lead A.G.E. Crosslink Breaker, ALT-711. These findings of efficacy and safety support the potential for ALT-711 as a novel, first-in- class anti-hypertensive agent with characteristics that are clearly differentiated from existing blood pressure agents for the treatment of uncontrolled systolic hypertension.
ALT-711 treatment resulted in highly significant lowering of systolic blood pressures in patients with a baseline systolic ABPM of 140 mm Hg or greater, with little concurrent effect on diastolic blood pressure readings. Trends were similar for both three and six months. The treatment effects were greatest in patients with higher starting systolic blood pressure readings, with no statistically meaningful effect in patients with a systolic blood pressure below 140 mm Hg. Furthermore, ALT-711's effect was persistent in the presence of increasing numbers of background medicines, rather than reduced as is generally seen with current incremental therapies. These findings further support the hypothesis that ALT-711 works best in patients with more serious baseline hypertension via a mechanism of action unlike any currently marketed high blood pressure drug.
Placebo Subtracted Changes in 24 hr ABPM at 6 Months, ALT-711 35 mg Dose
Change In SBP (mm Hg) Change In DBP (mm Hg)
Baseline ABPM SBP >\=1 MED >\=2 MEDS >\=1 MED >\=2 MEDS
< 140mm Hg 6.1 6.5 5.0 4.8
>\= 140mm Hg -6.0** -10.0** -2.5 -4.6**
>\= 150mm Hg -9.3* -14.4** -3.9 -6.3**
* P<\=0.05; ** P<\=0.01
The clinical response to ALT-711 was more frequent in all treatment groups vs. placebo; in the most effective dosing group, there were twice as many responders as in the placebo group. ALT-711 was remarkably safe and well tolerated across all dosing groups.
"The new data on ALT-711 look promising," said Stanley Franklin, M.D., Clinical Professor of Medicine and Associate Medical Director, University of California, Irvine, Heart Disease Prevention Program and a contributing author of the seminal Framingham Heart and NHANES III hypertension studies. "Showing a significant reduction in SBP without a corresponding reduction in DBP strongly suggests that this drug is reducing arterial stiffness without a corresponding reduction in peripheral resistance."
These results define the ABPM data further than what has been announced previously, showing the relationship of efficacy with baseline systolic blood pressures and number of background medications. Further analyses and discussion of ALT-711's clinical and preclinical data will be presented at an upcoming scientific forum in May 2004.
The Phase 2b SAPPHIRE (Systolic And Pulse Pressure Hemodynamic Improvement by Restoring Elasticity) and SILVER (Systolic Hypertension Interaction with Left VEntricular Remodeling) trial evaluated ALT-711's effectiveness in approximately 800 patients having elevated systolic blood pressure (systolic hypertension) without or with enlargement of the left ventricle of the heart (left ventricular hypertrophy or LVH). The trial was dose-ranging, double- blind, placebo-controlled and conducted at over 60 sites nationwide.
Alteon announced the initial results of the SAPPHIRE/SILVER trial in July 2003. 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, did not demonstrate statistical significance as compared to placebo. The data analysis was confounded by a 6-10 mm Hg drop in systolic blood pressures in all arms of the SAPPHIRE /SILVER trial, 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. As reported at that time, a pre-specified secondary analysis of ABPM measurements in all patients who completed the study demonstrated a blood pressure lowering effect at lower doses of approximately 4 mm Hg net of placebo. There was no significant placebo effect noted in the ABPM measurements.
"The further analysis of the Phase 2b SAPPHIRE/SILVER trial has provided us with a wealth of meaningful data that supports and guides the continued development of ALT-711 for uncontrolled systolic hypertension," said Kenneth I. Moch, President and CEO. "We have learned a great deal about the characteristics of patients who are likely to respond best to ALT-711 and have incorporated these insights into the design of additional clinical trials to confirm our findings. The next clinical trial of ALT-711 in systolic hypertension will begin during the first half of this year, as will the next trial of ALT-711 in heart failure."
About Alteon
Alteon is developing several new classes of drugs that reverse or slow down diseases of aging and complications of diabetes. These compounds have an impact on a fundamental pathological process caused by protein-glucose complexes called Advanced Glycation End-products (A.G.E.s). The formation and crosslinking of A.G.E.s lead to a loss of flexibility and function in body tissues, organs and vessels and have been shown to be a causative factor in many age-related diseases and diabetic complications. Alteon has created a library of novel classes of compounds targeting the A.G.E. Pathway. These include A.G.E. Crosslink Breakers, A.G.E. Formation Inhibitors and Glucose Lowering Agents. Alteon's lead compound ALT-711, the only A.G.E. Crosslink Breaker in advanced human testing, has demonstrated safety and efficacy in several Phase 2 trials and is actively being developed for systolic hypertension and heart failure. For more information on Alteon, visit the company's website at www.alteon.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, those relating to technology and product development (including the possibility that early clinical trial results may not be predictive of results that will be obtained in large-scale testing or that any clinical trials will not demonstrate sufficient safety and efficacy to obtain requisite approvals or will not result in marketable products), regulatory approval processes, intellectual property rights and litigation, competitive products, ability to obtain financing, and other risks identified in Alteon's filings with the Securities and Exchange Commission. The information contained in this press release is accurate as of the date indicated. Actual results, events or performance may differ materially. Alteon 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.
PLEASE NOTE: Alteon will be presenting at the BIO CEO & Investor Conference in New York City on Wednesday, February 25th at 12 noon. This presentation will be webcast and can be accessed at the investor relations section of our website, www.alteon.com |
