SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM 8-K
CURRENT REPORT
PURSUANT TO SECTION 13 or 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934
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Date of report (Date of earliest event reported) October 23, 2001
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ALTEON INC.
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(Exact Name of Registrant as Specified in Charter)
Delaware 0-19529 13-3304550
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(State or Other Juris- (Commission (I.R.S. Employer
diction of Incorporation) File Number) Identification No.)
170 Williams Drive, Ramsey, New Jersey 07446
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(Address of Principal Executive Offices) (Zip Code)
Registrant's telephone number, including area code (201) 934-5000
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(Former Name or Former Address, If Changed Since Last Report)
Item 5. Other Events
On October 23, 2001 Alteon Inc. issued the following press release:
ALTEON INITIATES SECOND PHASE IIb TRIAL OF ALT-711 IN SYSTOLIC HYPERTENSION
RAMSEY, N.J., Oct. 23 /PRNewswire/ -- Alteon Inc. (Amex: ALT) announced
today that it has initiated a second Phase IIb trial of ALT-711, an orally
active drug that has demonstrated a broad beneficial effect in reversing
cardiovascular disease. The SILVER (Systolic Hypertension Interaction with
Left VEntricular Remodeling) trial will evaluate the blood pressure
lowering effects of ALT-711 in patients who have systolic hypertension and
left ventricular hypertrophy (LVH), a thickening of the heart tissue that
results from hypertension. LVH can lead to decreased cardiac output, the
inability to meet the circulatory needs of the body, and to heart failure
itself.
ALT-711 is concurrently being tested in humans with systolic hypertension
alone in the Phase IIb SAPPHIRE (Systolic And Pulse Pressure Hemodynamic
Improvement by Restoring Elasticity) trial, which was initiated in July
2001. Patients who are excluded as patients in the SAPPHIRE trial because
of LVH will be target candidates for the SILVER trial. The SAPPHIRE and
SILVER trials collectively will enroll 630 patients, with data expected in
the second half of 2002.
ALT-711 is the most clinically advanced drug in a new class of compounds,
known as Advanced Glycosylation End-product (A.G.E.) Crosslink Breakers,
which were discovered by Alteon. By "breaking" the pathological bonds that
cause tissues, organs and vessels to stiffen and lose function over time,
ALT-711 has demonstrated the ability to reverse certain age-related and
diabetes-related conditions. In a 93-patient Phase IIa clinical trial,
treatment with ALT-711 resulted in statistically significant and clinically
meaningful effects of increasing vascular wall elasticity and lowering
pulse pressure, each major contributing factors in cardiovascular disease.
"The SILVER trial is an important addition to our overall clinical
strategy," said Robert C. deGroof, Senior Vice President, Scientific
Affairs. "Evaluating the interaction between systolic hypertension and LVH
in the SILVER trial will help us build a solid foundation for a subsequent
pivotal Phase III program."
"The results from these trials are critical in providing further proof of
the value of A.G.E. compounds and ALT-711 in treating cardiovascular
disease," said Kenneth I. Moch, Chairman and CEO. "Its mechanism of action
is new and novel, and is unrelated to that of any pharmaceutical agent
either currently prescribed or in clinical development. Importantly, as in
our Phase IIa trial, the ongoing SAPPHIRE and SILVER trials will use
ALT-711 in addition to currently prescribed hypertension medications.
Market estimates indicate that 15-20 million patients in the U.S. suffer
from systolic hypertension."
Additional background information on systolic hypertension follows this
press release.
The SILVER and SAPPHIRE Trials
The SILVER trial will test ALT-711 in 180 patients at the approximately 40
sites
throughout the United States that are also conducting the ongoing 450
patient SAPPHIRE trial. Recruited patients will be randomized to one of two
treatment arms and receive ALT-711 or placebo tablets once a day for three
months, in addition to their existing medications. Patients enrolled in the
trial must be older than 50 years of age, have a systolic blood pressure of
greater than 160 mmHg and diastolic blood pressure of less than 90 mmHg,
and have thickening of the left ventricle of the heart as measured by
echocardiography. The trial will include males and female, non-diabetic and
diabetic patients. As with the SAPPHIRE trial, the primary endpoints of the
study will be the change in systolic blood pressure, and change in pulse
pressure (the difference between the systolic and diastolic blood
pressure). In addition, secondary endpoints will include additional blood
pressure measurements and change in certain urological characteristics.
ALT-711: Consistent Beneficial Data in Cardiovascular Disease
Through its unique mechanism of action, ALT-711 is the first compound in
development that breaks A.G.E.-derived crosslinks between proteins,
potentially restoring flexibility and function to tissues, vessels and
organs throughout the body. Normal structure and function is preserved
while abnormal crosslinking is reduced. Evidence of the positive effect of
ALT-711 on the cardiovascular system continues to grow. In a Phase IIa
human trial, ALT-711 was shown to restore the cardiovascular system to a
younger state by reversing the stiffening of the arteries that occurs in
aging patients, increasing the ability of the diseased large arteries to
stretch by 11-18%, and bringing them approximately 30% back to normal. The
study was designated as "breakthrough information" and selected for "Rapid
Track" publication in Circulation: Journal of the American Heart
Association, and was published in the September 25, 2001, issue of the
journal. Earlier in 2001, the ALT-711 Phase IIa data was featured at the
March 2001 American College of Cardiology (ACC) meeting in a "Late Breaking
Clinical Trials Special Scientific Session" and further chosen as one of
four highlights of the Hypertension Section of the ACC meeting.
Evidence that ALT-711 may be effective for improving cardiovascular
remodeling in hypertension was presented by University of Minnesota
researchers at the American Heart Association's 55th Annual Fall Conference
and Scientific Sessions of the Council for High Blood Pressure Research on
September 23, 2001. This preclinical study demonstrated the ability of
ALT-711 to decrease the thickening of the heart and improve the function of
the endothelium in rats with hypertension. The research team tested
ALT-711's ability to selectively break the cross-linking of collagen that
contributes to cardiovascular disease in aging and diabetes. ALT-711
normalized left ventricular fibrosis, or the thickening of the left
ventricle of the heart, and improved the function of the endothelium, the
part of the cardiovascular system that regulates both the relaxation and
contraction of blood vessels and contributes to the maintenance of the
vascular structure.
Preclinical studies of ALT-711 conducted by researchers from The National
Institute on Aging and Johns Hopkins Geriatric Center demonstrated the
ability of the compound to significantly reduce arterial stiffness in
elderly monkeys. Another study, in aged dogs, found that administration of
ALT-711 for one month resulted in an approximate 40% decrease in
age-related ventricular stiffness. This decrease was accompanied by an
overall improvement in cardiac function. Reductions in blood pressure have
also been observed in preclinical
models of diabetic hypertension.
About Alteon
Alteon is developing several new classes of drugs that reverse or slow down
diseases of aging and complications of diabetes. These compounds impact a
fundamental pathological process caused by protein-glucose complexes called
Advanced Glycosylation End-products (A.G.E.s). The formation and
crosslinking of A.G.E.s are an inevitable part of the aging process that
lead to a loss of flexibility and function in body tissues, organs and
vessels. The company is initially developing therapies for cardiovascular
and kidney diseases in older or diabetic individuals.
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. The Company's lead A.G.E. Crosslink
Breaker, ALT-711, is being evaluated in two Phase IIb trials, SAPPHIRE and
SILVER, for cardiovascular diseases. The compound is also under
investigation for end-stage renal disease patients undergoing peritoneal
dialysis, and is serving as a clinical prototype in other conditions where
A.G.E. crosslinking is a cause of disease, such as uropathy and diabetic
retinopathy. For more information on Alteon, visit the company's web site
at http://www.alteonpharma.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.
BACKGROUNDER
Systolic Hypertension: An Unmet Medical Need in Aging
Systolic hypertension is the most common form of hypertension in people
over age 50, with an estimated prevalence of 15-20 million people in the
U.S. alone. Yet it is the type of hypertension least likely to be well
treated, according to a recent study published in the March 16, 2001
edition of Hypertension, a journal of the American Heart Association.
Systolic hypertension is a consequence of the age-related stiffening of the
large arteries, and it is defined as elevated systolic blood pressure
(above 140 mmHg) in conjunction with normal diastolic blood pressure (below
90 mmHg). It is characterized by an increased pulse pressure, defined as
the difference between systolic and diastolic blood pressures. The
prevalence of hypertension increases with age, with systolic hypertension
becoming far more common than diastolic hypertension.
Traditionally, treatment of hypertension has focused on controlling
diastolic pressure. Current hypertension therapies, including diuretics,
ACE inhibitors, beta blockers, calcium channel blockers and angiotensin
receptor blockers have an effect on lowering both systolic and diastolic
pressures. Treatment is therefore limited, as a patient may become
hypotensive with too low a diastolic pressure.
A recent editorial in The New England Journal of Medicine [August 16, 2001]
stated that the control of hypertension is an important national priority,
and that clinical practice needs to shift focus to the management of
systolic rather than diastolic hypertension. As documented in this issue of
the Journal, most cases of uncontrolled hypertension are in persons with
elevated systolic blood pressure, particularly in elderly adults. The
epidemiological data indicate that systolic blood pressure is significantly
more important than diastolic blood pressure as a determinant of
cardiovascular risk in this group of patients.
The focus on systolic pressure began to increase in the 1990's with the
results from the Systolic Hypertension in the Elderly Program (SHEP) trial
and other epidemiological data that demonstrated that the level of systolic
blood pressure is a better predictor of cardiovascular events including
stroke, coronary heart disease, and heart failure. A systolic blood
pressure higher than 160 mmHg has been shown to double all-cause mortality,
triple cardiovascular mortality, particularly in women, and more than
double cardiovascular morbidity in both sexes. Similarly, elevated pulse
pressure is increasingly being recognized as a risk factor for
cardiovascular disease. The Framingham Study and others have demonstrated
that a reduction in pulse pressure is associated with a significant risk
reduction in cardiovascular death.
However, these findings have not yet been reflected in clinical practice
due in part to the fact that there are no approved agents that selectively
lower systolic blood pressure. The NEJM editorial states that physicians
are often reluctant to treat systolic hypertension for fear of doing harm.
Alteon's proprietary class of A.G.E. Crosslink Breakers, and lead compound
ALT-711, may specifically address this treatment issue by directly
targeting the stiffening of the arteries that contributes to systolic
hypertension. ALT-711 is currently two Phase IIb trials, the SAPPHIRE
(Systolic And Pulse Pressure Hemodynamic Improvement by Restoring
Elasticity) and SILVER (Systolic Hypertension Interaction with Left
VEntricular Remodeling) trials in patients with systolic hypertension, with
data expected in the second half of 2002.
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Pursuant to the requirements of the Securities Exchange Act of 1934,
the Registrant has duly caused this report to be signed on its behalf by the
undersigned hereunto duly authorized.
Alteon Inc.
By: /s/ Kenneth I. Moch
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Kenneth I. Moch
President and Chief
Executive Officer
Dated: October 23, 2001