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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) July 9, 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)
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Item 5. Other Events
On July 9, 2001 Alteon Inc. issued the following press release:
ALTEON INITIATES PHASE IIB 'SAPPHIRE' TRIAL OF ALT-711 IN SYSTOLIC HYPERTENSION
- MOST COMMON FORM OF HYPERTENSION IN THOSE OVER 50, AND TYPE LEAST LIKELY TO BE
WELL TREATED
RAMSEY, N.J., July 9 /PRNewswire/ -- Alteon Inc. (Amex: ALT) announced today
that it has begun the Phase IIb SAPPHIRE (Systolic And Pulse Pressure
Hemodynamic Improvement by Restoring Elasticity) trial of Alteon's lead A.G.E.
Crosslink Breaker compound, ALT-711, in patients with isolated systolic
hypertension (ISH). The SAPPHIRE trial will build upon positive data from a
recent Phase IIa human trial to further evaluate ALT-711's ability to lower
systolic blood pressure and pulse pressure in aging and diabetic patients.
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 recent Phase
IIa clinical trial in cardiovascular disease, treatment with ALT- 711 resulted
in statistically significant and clinically meaningful effects of increasing
vascular wall elasticity and lowering pulse pressure. 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. No approved drug for high blood pressure directly targets the
underlying age-related stiffening that results in ISH, and thus this condition
represents a major unmet medical need.
The SAPPHIRE Trial
In the SAPPHIRE trial, ALT-711, an orally active compound, will be tested in
450 patients at approximately 40 sites throughout the United States. Recruited
patients will receive ALT-711 tablets once a day for six months, in addition
to their existing medications. The study will consist of five treatment arms,
comprised of four different dose levels of ALT-711 plus placebo. Patients
enrolled in the trial must be older than 50 years of age and have systolic
blood pressure of greater than 160 mmHg and diastolic blood pressure of less
than 90 mmHg. The trial will include both non-diabetic and diabetic patients.
The SAPPHIRE trial extends the range of doses and the dosing period of ALT-711
defined in the previous Phase IIa trial. In the Phase IIa trial of 93
patients, treatment with ALT-711 over an 8-week period resulted in a
statistically significant reduction in pulse pressure (5 mmHg net decrease at
day 56, pAmerican College of Cardiology meeting.
Consistent Results Across Species
Preclinical testing has clearly demonstrated the ability of ALT-711 to reverse
age-related and diabetes-related cardiovascular disease and restore function
to the cardiovascular system. "It is important to emphasize that our data thus
far has been consistent across all species that we have tested," said Robert
C. deGroof, Ph.D., Senior Vice President, Scientific Affairs. "In preclinical
evaluations, ALT-711 reversed stiffening of the aorta in
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rodents, canines and non-human primates, similar to what recently has been
observed in humans. The SAPPHIRE trial has been designed to confirm all of
these results and to further determine effects of ALT-711 over a longer period
of time and a wider range of dosages. It is expected to provide a solid
foundation for a subsequent Phase III program."
Isolated Systolic Hypertension and the Importance of Pulse Pressure
Isolated Systolic Hypertension is the most common form of hypertension in
people over age 50, and most recent statistics estimate its prevalence at over
20 million in the U.S. alone. It is defined as elevated systolic blood
pressure (above 140 mmHg) in conjunction with normal diastolic blood pressure
(below 90 mmHg), and 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. 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.
Traditionally, treatment of hypertension has focused on controlling diastolic
pressure. 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.
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 can become hypotensive with too low a
diastolic pressure.
A.G.E. Crosslink Breakers, and lead compound ALT-711, may specifically address
this treatment issue. "Our results to date suggest that we offer an
opportunity to provide an option for ISH through a novel mechanism of action,"
said Kenneth I. Moch, President and Chief Executive Officer. "We have been
able to narrow the gap between the systolic and diastolic pressures, and we
look forward to confirming these results in the SAPPHIRE trial. As ALT-711
targets a major market with a differentiated and clearly unmet medical need,
the results from this trial will be greatly anticipated. We are very pleased
to be able to initiate this important trial in our expected time frame, and
intend to maintain our diligence in this pursuit."
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A.G.E. Crosslink Breakers and ALT-711
Advanced Glycosylation End-products (A.G.E.s) are permanent glucose structures
that form when glucose binds to the surface of proteins. Many of these
proteins, including structural proteins such as collagen and elastin, play an
integral role in the maintenance of cardiovascular elasticity function and
vascular wall integrity. Diabetic individuals form excessive amounts of
A.G.E.s earlier in life than non-diabetic individuals.
This process can impair the normal function of organs that depend on
flexibility for normal function, such as blood vessels and cardiac muscle. The
formation of A.G.E. Crosslinks leads to increased stiffness of tissues,
abnormal protein accumulation and organ dysfunction, which together cause many
of the complications of aging and diabetes. 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.
ALT-711 is the first in the A.G.E. Crosslink Breaker class that has been shown
to reverse or "break" A.G.E. crosslinking, thereby restoring more normal
function to organs and tissues that have lost flexibility. Pharmacologic
intervention with ALT-711 directly targets the biochemical pathway leading to
the stiffness of the cardiovascular system. 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, ALT-711 does not disrupt
the natural enzymatic glycosylation sites or peptide bonds that are
responsible for maintaining the normal integrity of the collagen chain. Thus,
normal structure and function is preserved while abnormal crosslinking is
reduced.
About Alteon
Alteon is a leader in the discovery and development of novel pharmaceuticals
for the treatment of pathologies of aging and diabetes, based on reversing or
slowing 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 is an inevitable part of the aging process that leads
to a loss of flexibility and function in body tissues, organs and vessels. The
company is initially developing therapies for cardiovascular disease.
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 developed for the treatment of cardiovascular
disorders. ALT-711 demonstrated positive results in a recent Phase IIa
clinical trial and currently is being evaluated in the Phase IIb SAPPHIRE
clinical trial focused on isolated systolic hypertension. The compound is also
under investigation for end-stage renal disease patients receiving peritoneal
dialysis, a patient population that has significant cardiovascular disease.
ALT-711 is further serving as a clinical prototype in other conditions where
A.G.E. crosslinking is a cause of disease, such as uropathy and diabetic
retinopathy. Pimagedine, Alteon's lead A.G.E. Formation Inhibitor, is in
active clinical evaluation in diabetic neuropathy in cats. For more
information on Alteon, visit the company's web site at
http://www.alteonpharma.com.
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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.
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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: July 17, 2001