Wednesday January 3, 7:45 am Eastern Time
Press Release
SOURCE: Alteon Inc.
Alteon's ALT-711 Demonstrates Potential as
Novel Treatment for Isolated Systolic Hypertension
- Phase IIa Preliminary Results Show ALT-711 Provides Statistically Significant Decrease in
Pulse Pressure and Increase in Cardiovascular Compliance -
RAMSEY, N.J., Jan. 3 /PRNewswire/ -- Alteon Inc. (Amex: ALT - news) today announced positive results from a
Phase IIa clinical trial evaluating the safety, efficacy and pharmacology of ALT-711, a first of its kind Advanced
Glycosylation End-product Crosslink Breaker (A.G.E. Crosslink Breaker). The formation of A.G.E. Crosslinks is a
natural part of the aging process that can lead to stiffening and loss of function in tissues, organs and vessels
including large arteries.
Study results show that patients who received ALT-711 experienced a statistically significant reduction in the arterial
pulse pressure, defined by the difference between systolic and diastolic blood pressures. Results also show a
clinically relevant increase in large artery compliance, an indicator of greater vascular flexibility and volume capacity,
using a traditional measurement of the ratio of stroke volume to pulse pressure. Additionally, the drug was
well-tolerated.
The ability to decrease pulse pressure and increase large artery compliance offers an opportunity to provide a
treatment option specifically for isolated systolic hypertension (ISH), a currently unmet medical need. ISH, defined as
elevated systolic blood pressure (greater than 160 mmHg) accompanied by normal diastolic blood pressure (less than
90 mmHg), can result in a substantially increased risk of cardiovascular disease and death. ISH affects nearly eight
million Americans and is primarily a consequence of stiffening of the large arteries. ALT-711 is the first drug to show
activity against ISH by targeting stiff vessel disease that contributes to this form of hypertension.
``These study results are important because currently available cardiovascular treatments do not directly target
vascular stiffening and, as a result, are not optimal for the treatment of isolated systolic hypertension,'' said Edward
G. Lakatta, M.D., Chief of the Laboratory of Cardiovascular Science at The National Institute on Aging and an
investigator in this study. ``The ALT-711 results are exciting in that selective enhancement of large artery
distensibility with reduced pressure pulsation was achieved, providing a novel approach for the treatment of isolated
systolic hypertension.''
The Phase IIa human clinical trial was a double-blinded, placebo-controlled study evaluating the safety, efficacy and
pharmacology of ALT-711. The trial included 93 patients over the age of 50 with measurably stiffened
cardiovasculature including systolic blood pressure of at least 140 mmHg and pulse pressure of at least 60 mmHg.
Patients were randomized to receive 56 consecutive daily oral doses of either 210 mg of ALT-711 (n=62) or placebo
(n=31) during an 8-week period. During the study, which was conducted at nine U.S. clinical sites, patients were
evaluated for cardiovascular elasticity and function as measured by pulse pressure, cardiovascular compliance, pulse
wave velocity and cardiac output. Treatment with ALT-711 was in addition to all other medications.
``The results of this study represent a significant milestone for Alteon. The trial was designed to provide us with a
better understanding of ALT-711's potential therapeutic benefits to the cardiovascular system and, as a result, impart
meaningful guidance for the clinical direction of this compound,'' said Kenneth I. Moch, President and Chief
Executive Officer of Alteon. ``Based on these results, during 2001 Alteon plans to initiate Phase IIb efficacy trials to
further assess ALT-711's activity in isolated systolic hypertension. Additionally, the Company will continue to
evaluate the compound for other therapeutic applications.''
Preclinical testing showed that ALT-711 reversed aging- and diabetes-related cardiovascular disease and restored
function to the cardiovascular system. In preclinical evaluations, ALT-711 reversed stiffening of the aorta in rodents,
canines and non-human primates. Although a statistically significant effect was not seen in cardiac output and pulse
wave velocity as observed in preclinical trials, Alteon will continue to evaluate these measures in larger populations
over longer periods of time as part of the Phase IIb program in ISH.
``Alteon was founded on the belief that by targeting the A.G.E. pathway, we can treat the cause of certain aging- and
diabetes-related pathologies and reduce the severity and incidence of resulting diseases,'' said Robert C. deGroof,
Ph.D., Senior Vice President, Scientific Affairs of Alteon. ``This trial was an important step in proving our technology
platform and demonstrating the potential to reverse cardiovascular disease caused by pathologies of diabetes and
aging and, as a result, we believe that ALT-711 may represent a new frontier in cardiovascular medicine.''
A.G.E. Crosslink Breakers
Advanced Glycosylation End-products (A.G.E.s) are permanent glucose structures that form when glucose binds to
the surface of proteins. These structures interact with adjacent proteins to form pathological links called A.G.E.
Crosslinks. Diabetic individuals form excessive amounts of A.G.E.s earlier in life than non-diabetic individuals. The
formation of A.G.E. Crosslinks leads to increased stiffness of tissues, abnormal protein accumulation and organ
dysfunction, which result in many complications of aging and diabetes.
Structural proteins, such as collagen and elastin, play an integral role in the maintenance of cardiovascular elasticity
function and vascular wall integrity and are prime targets for A.G.E. crosslinking. This mechanical process can impair
the normal function of contractile organs, such as blood vessels and cardiac muscle, which depend on flexibility for
normal function. Loss of flexibility of the vasculature leads to isolated systolic hypertension, which creates increased
workload for the heart and may lead to myocardial hypertrophy and heart failure.
Cardiovascular Disease and Isolated Systolic Hypertension
According to the American Heart Association, nearly 60 million Americans have one or more types of cardiovascular
disease. Cardiovascular disease has been the number one killer of Americans since the early 1900's. Isolated systolic
hypertension is associated with a significantly increased risk of overall mortality, cardiovascular mortality and
congestive heart failure. The latest World Health Organization - International Society of Hypertension guidelines for
the management of hypertension emphasize the importance of pulse pressure and arterial stiffness as predictors of
cardiovascular risk. |
